Jian-Qiang Feng

Following the publication of this paper, and an Expression of Concern statement that was published to draw attention to the fact that the Editorial Office are in the process of consulting the authors regarding the fact that the photos shown in Fig. 5B and D were apparently matching images (doi: 10.3892/ijmm.2025.5618), we have been contacted again by another reader who has highlighted that Fig. 5C and F also contain an overlapping section, albeit that the image has been rotated through 90° and flipped vertically in panel (F). We have contacted the authors again, asking them to provide an explanation for the apparent anomalies in the presentation of Fig. 5 in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of these potential issues surrounding the scientific integrity of this paper, we are issuing a second Expression of Concern statement to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 28: 397‑403, 2011; DOI: 10.3892/ijmm.2011.682]

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the photos shown in Fig. 5B and D were apparently matching images, such that data which were intended to have shown the results of differently performed mitochondrial protection experiments appeared to have been derived from the same original source. The authors were contacted by the Editorial Office to offer an explanation for the apparent anomaly in the presentation of the data in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 28: 397‑403, 2011; DOI: 10.3892/ijmm.2011.682]

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, for the cell viability experiments shown in Fig. 2E, the ‘Control’ image (top row) and the ‘ZnPP’ image (bottom row) appeared to show an overlapping section of data, such that data which were intended to have shown the results of differently performed experiments appeared to have been derived from the same original source. The authors were contacted by the Editorial Office to offer an explanation for the apparent anomaly in the presentation of the data in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 30: 314‑320, 2012; DOI: 10.3892/ijmm.2012.1002]

Summary: Aims: Connexin 43 (Cx43) has been reported to be involved in neuropathic pain, but whether it contributes to morphine antinociceptive tolerance remains unknown. The present study investigated the role of spinal Cx43 in the development of morphine tolerance and its mechanisms in rats.Methods: Morphine tolerance was induced by intrathecal (i.t.) administration of morphine (15 μg) daily for seven consecutive days. The analgesia effect was assessed by hot‐water tail‐flick test. Expression of proteins was detected by Western blot and immunohistochemistry assay.Results: Chronic morphine markedly increased the expression of spinal Cx43. Gap26, a specific Cx43 mimic peptide, attenuated not only morphine antinociceptive tolerance, but also the up‐regulation of spinal Cx43 expression, the activation of astrocytes, and N‐methyl‐D‐aspartic acid (NMDA) receptors (NR1 and NR2B subunits), as well as the decreased GLT‐1 expression induced by chronic morphine. MK‐801, a noncompetitive NMDA receptors antagonist, suppressed the chronic morphine‐induced spinal Cx43 up‐regulation, astrocytes activation and decline of GLT‐1 expression.Conclusions: The spinal astrocytic Cx43 contributes to the development of morphine antinociceptive tolerance by activating astrocytes and NMDA receptors, and inhibiting GLT‐1 expression. We also demonstrate that the role of interaction between the spinal astrocytic Cx43 and neuronal NMDA receptors is important in morphine tolerant rats.

A number of studies have demonstrated that inflammation plays a role in doxorubicin (DOX)-induced cardiotoxicity. However, the molecular mechanism by which DOX induces cardiac inflammation has yet to be fully elucidated. The present study aimed to investigate the role of the p38 mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) pathway in DOX-induced inflammation and cytotoxicity. The results of our study demonstrated that the exposure of H9c2 cardiac cells to DOX reduced cell viability and stimulated an inflammatory response, as demonstrated by an increase in the levels of interleukin-1β (IL-1β) and IL-6, as well as tumor necrosis factor-α (TNF-α) production. Notably, DOX exposure induced the overexpression of phosphorylated p38 MAPK and phosphorylation of the NF-κB p65 subunit, which was markedly inhibited by SB203580, a specific inhibitor of p38 MAPK. The inhibition of NF-κB by pyrrolidine dithiocarbamate (PDTC), a selective inhibitor of NF-κB, significantly ameliorated DOX-induced inflammation, leading to a decrease in the levels of IL-1β and IL-6, as well as TNF-α production in H9c2 cells. The pretreatment of H9c2 cells with either SB203580 or PDTC before exposure to DOX significantly attenuated DOX-induced cytotoxicity. In conclusion, our study provides novel data demonstrating that the p38 MAPK/NF-κB pathway is important in the induction of DOX-induced inflammation and cytotoxicity in H9c2 cardiac myocytes.

The roles of hydrogen sulfide (H₂S) and endoplasmic reticulum (ER) stress in doxorubicin (DOX)-induced cardiotoxicity are still unclear. This study aimed to dissect the hypothesis that H₂S could protect H9c2 cells against DOX-induced cardiotoxicity by inhibiting ER stress. Our results showed that exposure of H9c2 cells to DOX significantly inhibited the expression and activity of cystathionine-γ-lyase (CSE), a synthetase of H₂S, accompanied by the decreased cell viability and the increased reactive oxygen species (ROS) accumulation. In addition, exposure of cells to H₂O₂ (an exogenous ROS) mimicked the inhibitory effect of DOX on the expression and activity of CSE. Pretreatment with N-acetyl-l-cysteine (NAC) (a ROS scavenger) attenuated intracellular ROS accumulation, cytotoxicity, and the inhibition of expression and activity of CSE induced by DOX. Notably, the ER stress-related proteins, including glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) were obviously upregulated in DOX-treated H9c2 cells. Pretreatment with sodium hydrosulfide (NaHS, a H₂S donor) before DOX exposure markedly suppressed DOX-induced overexpressions of GRP78 and CHOP, cytotoxicity and oxidative stress. In conclusion, we have demonstrated that ROS-mediated inhibition of CSE is involved in DOX-induced cytotoxicity in H9c2 cells, and that exogenous H₂S can confer protection against DOX-induced cardiotoxicity partly through inhibition of ER stress.

Hydrogen sulfide (H₂S) has been shown to exert cardioprotective effects. However, the roles of extracellular signal-regulated protein kinases 1/2 (ERK1/2) in H₂S-induced cardioprotection have not been completely elucidated. In this study, cobalt chloride (CoCl₂), a chemical hypoxia mimetic agent, was applied to treat H9c2 cells to establish a chemical hypoxia-induced cardiomyocyte injury model. The results showed that pretreatment with NaHS (a donor of H₂S) before exposure to CoCl₂ attenuated the decreased cell viability, the increased apoptosis rate, the loss of mitochondrial membrane potential (ΔΨm), and the intracellular accumulation of reactive oxygen species (ROS) in H9c2 cells. Exposure of H9c2 cells to CoCl₂ or hydrogen peroxide (H₂O₂) upregulated expression of phosphorylated (p) ERK1/2, which was reduced by pretreatment with NaHS or N-acetyl-l-cysteine, a ROS scavenger. More importantly, U0126, a selective inhibitor of ERK1/2, mimicked the above cytoprotection of H₂S against CoCl₂-induced injury in H9c2 cells. In conclusion, these results indicate that H₂S protects H9c2 cells against chemical hypoxia-induced injury partially by inhibiting ROS-mediated activation of ERK1/2.

Hydrogen sulfide (H₂S) has been shown to protect against oxidative stress injury and inflammation in various hypoxia-induced insult models. However, it remains unknown whether H₂S protects human skin keratinocytes (HaCaT cells) against chemical hypoxia-induced damage. In the current study, HaCaT cells were treated with cobalt chloride (CoCl₂), a well known hypoxia mimetic agent, to establish a chemical hypoxia-induced cell injury model. Our findings showed that pretreatment of HaCaT cells with NaHS (a donor of H₂S) for 30 min before exposure to CoCl₂ for 24 h significantly attenuated CoCl₂-induced injuries and inflammatory responses, evidenced by increases in cell viability and GSH level and decreases in ROS generation and secretions of IL-1β, IL-6 and IL-8. In addition, pretreatment with NaHS markedly reduced CoCl₂-induced COX-2 overexpression and PGE₂ secretion as well as intranuclear NF-κB p65 subunit accumulation (the central step of NF-κB activation). Similar to the protective effect of H₂S, both NS-398 (a selective COX-2 inhibitor) and PDTC (a selective NF-κB inhibitor) depressed not only CoCl₂-induced cytotoxicity, but also the secretions of IL-1β, IL-6 and IL-8. Importantly, PDTC obviously attenuated overexpression of COX-2 induced by CoCl₂. Notably, NAC, a ROS scavenger, conferred a similar protective effect of H₂S against CoCl₂-induced insults and inflammatory responses. Taken together, the findings of the present study have demonstrated for the first time that H₂S protects HaCaT cells against CoCl₂-induced injuries and inflammatory responses through inhibition of ROS-activated NF-κB/COX-2 pathway.