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Bioimaging probes for accurately monitoring apoptosis process have extensive significance for cell biological studies and clinical investigations. Herein, novel multifunctional peptide-tailored gold nanoclusters (AuNCs) have been developed for real-time imaging of caspase-indicated cell apoptosis. The AuNCs nanoprobe was facilely prepared by a one-step peptide-mediated biomineralization with the dye (TRAMA)-tagged peptides specific to caspase 3 as both template agents and the signal switch. Unlike conventional FRET-based fluorescent probes of caspase activity, these nanoprobes relied on the unique quenching effect of AuNCs through the nanosurface energy transfer (NSET) from dye to AuNCs. Intracellular caspase 3 activation cleaved the substrate peptide and released the dye from AuNCs, leading to a significant fluorescence lighting-up for sensitive and continuous analysis of caspase 3 activity in live cells, with a high signal-background ratio, wide linear range (32 pM-10 nM), and ultralow detection limit (12 pM). Moreover, this versatile AuNCs nanoprobe can serve as a theranostic platform via codisplaying pro-apoptotic and detecting peptides, which allows in situ activation and real-time monitoring of apoptosis in cancer cells. These results indicate that the AuNCs nanoprobe provides a smart molecular imaging and therapeutic agent targeted to cell apoptosis, which has great potential for apoptosis-related diagnosis and precision chemotherapy.

Neuroregeneration and apoptosis are two important pathophysiologic changes after spinal cord injury (SCI), but their underlying mechanisms remain unclear. MicroRNAs (miRNAs) play a crucial role in the regulation of neuroregeneration and neuronal apoptosis, research areas that have been greatly expanded in recent years. Here, using miRNA arrays to profile miRNA transcriptomes, we demonstrated that miR-127-3p was significantly down-regulated after spinal cord transection (SCT). Then, bioinformatics analyses and experimental detection showed that miR-127-3p exhibited specific effects on the regulation of neurite outgrowth and the induction of neuronal apoptosis by regulating the expression of the mitochondrial membrane protein mitoNEET. Moreover, knockdown of MitoNEET leaded to neuronal loss and apoptosis in primary cultured spinal neurons. This study therefore revealed that miR-127-3p, which targets mitoNEET, plays a vital role in regulating neurite outgrowth and neuronal apoptosis after SCT. Thus, modificatioin of the mitoNEET expression, such as mitoNEET activition may provide a new strategy for the treatment of SCI in preclinical trials.

Background & Objective: Survivin is specifically overexpressed in tumor tissues. Many reports have shown that the abrogation of its functions is useful for tumor therapy. RNA interference is a new technique that proved to be effective for suppressing gene expression. The aim of this study was to construct a siRNA expression plasmid against gene survivin, and then to assess its functions on breast cancer cells MCF-7., Methods: A survivin siRNA plasmid was constructed using a mU6pro vector contained U6 promotor, the expression change of survivin was examined by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis after the plasmid had been transfected into MCF-7 cells, and the effect of the plasmid on the cell cycle and cell proliferation was analyzed by flow cytometry and MTT method,respectively., Results: Survivin siRNA plasmid knocked down survivin expression in MCF-7 cells obviously, arrested the cell cycle in G1 phase, inhibited the cell proliferation significantly, and promoted cell apoptosis in a tendency., Conclusion: Survivin expression was knocked down at mRNA and protein levels by RNAi.

Nasopharyngeal carcinoma (NPC) is a malignant tumor originating in the nasopharyngeal epithelium with a high incidence in southern China and parts of Southeast Asia. The current treatment methods are mainly radiotherapy and chemotherapy. However, they often have side effects and are not suitable for long‐term exposure. Natural products have received more and more attention in cancer prevention and treatment because of their its high efficiency, low toxic side effects, and low toxicity. Natural products can serve as a viable alternative, and this study aimed to review the efficacy and mechanisms of natural products in the treatment of NPC by examining previous literature. Most natural products act by inhibiting cell proliferation, metastasis, inducing cell cycle arrest, and apoptosis. Although further research is needed to verify their effectiveness and safety, natural products can significantly improve the treatment of NPC. [ABSTRACT FROM AUTHOR]

Objective: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. Methods: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. Results: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. Conclusions: Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice. [ABSTRACT FROM AUTHOR]

Background. Kidney stone disease induces chronic renal insufficiency by crystal-induced renal tubular epithelial cell injury. It has been reported that the prevalence of kidney stone disease is increasing, accompanied by the high recurrence rate. Alkaline mineral water has been reported to possess beneficial effects to attenuate inflammation. Here, we explored the potential protective effects and underlying mechanisms of alkaline mineral water against calcium oxalate-induced kidney injury. Methods. We performed the mice kidney stone model by administering glyoxylate at 100 mg/kg once daily for 7 days. To assess the effects of alkaline mineral water on oxalate-induced kidney injury, mice drank different water (distilled water, natural mineral water at pH = 8.0, as well as natural mineral water at pH = 9.3) for 7 days, respectively, followed by glyoxylate exposure. After collection, crystal formation, kidney injury and cell apoptosis, fibrosis, oxidative stress, as well as inflammation were measured. Results. Our results showed that glyoxylate treatment led to kidney crystal formation and fibrosis, which can be attenuated by drinking alkaline mineral water. Furthermore, alkaline mineral water also reduced kidney injury and cell apoptosis, oxidative stress, and inflammation. Conclusion. Alkaline mineral water supplement prevents progression of glyoxylate-induced kidney stones through alleviating oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

GABA is a dominant inhibitory neurotransmitter in the brain and A type GABA receptor (GABAAR) phosphorylation is critical for GABA-mediated inhibitory effect. However, its role in the neuroprotective effect of sodium valproate (VPA), a prevalent drug for treating patients with epilepsy, remains elusive. The present study was conducted to explore the role of GABAAR phosphorylation in the neuroprotection of VPA against a kainic acid-induced epileptic rat model and the potential molecular mechanisms. Neuronal apoptosis was evaluated by TUNEL assay, PI/Annexin V double staining, caspase-3 activity detection and Bax and Bcl-2 proteins expression via Western blot analysis. The primary rat hippocampal neurons were cultivated and cell viability was measured by CCK8 detection following KA- or free Mg2+-induced neuronal impairment. Our results found that VPA treatment significantly reduced neuronal apoptosis in the KA-induced rat model (including reductions of TUNEL-positive cells, caspase-3 activity and Bax protein expression, and increase of Bcl-2 protein level). In the in vitro experiments, VPA at the concentration of 1 mM for 24 h also increased cell survival and suppressed cell apoptosis in KA- or no Mg2+-induced models via CCK8 assay and PI/Annexin V double staining, respectively. What is more important, the phosphorylation of γ2 subunit at serine 327 residue for GABAAR was found to be robustly enhanced both in the KA-induced epileptic rat model and neuronal cultures following KA exposure after VPA treatment, while no evident alteration was found in terms of GABAAR β3 phosphorylation (408 or 409 serine residue). Additionally, pharmacological inhibition of protein kinase C (PKC) clearly abrogated the neuroprotective potential of VPA against KA- or free Mg2+-associated neuronal injury, indicating a critical role of PKC in the effect of GABAAR γ2 serine 327 phosphorylation in VPA’s protection. In summary, our work reveals that VPA mitigates neuronal apoptosis in KA-triggered epileptic seizures, at least, via augmenting PKC-dependent GABAAR γ2 phosphorylation at serine 327 residue. [ABSTRACT FROM AUTHOR]

Histone deacetylase (HDAC) inhibitors have recently emerged as a new class of anticancer agents. As a classical HDAC inhibitor, trichostatin A (TSA) has been shown to possess many anticancer activities such as induction of cell cycle arrest, promotion of cell death, and enhancement of radiosensitity. In our previous work, we found that TSA treatment induced Rad9 gene expression, which suggested that Rad9 might play a role in TSA-induced biological effects. As Rad9 is involved in maintaining genomic integrity, we further analyzed the DNA damage induced by TSA and combined with Rad9 knockdown in esophageal cancer cells (ESCCs). Our results showed that TSA treatment alone induced significantly DNA damage in ESCC cells. Simultaneously, TSA also induced Rad9 gene expression both at transcriptional and translational levels in EC109 cells, but not in KYSE150 cells. Further, the induction of Rad9 by TSA was accompanied with increased level of histone H3K9 acetylation in Rad9 promoter region. To understand the role of Rad9 in TSA-induced DNA damage, Rad9 gene expression was efficiently knocked down by small interfering RNA (siRNA), which led to enhanced DNA damage and cell death induced by TSA. Our data suggested that Rad9 plays an important role in DNA damage, which is related to the biological effects of TSA. [ABSTRACT FROM AUTHOR]