Translational selenium nanoparticles boost GPx1 activation to reverse HAdV-14 virus-induced oxidative damage.

Human adenovirus (HAdV) can cause severe respiratory infections in immunocompromised patients, but its clinical treatment is seriously limited by side effects of drugs such as poor efficacy, low bioavailability and severe nephrotoxicity. Trace element selenium (Se) has been found will affect the disease progression of pneumonia, but its antivirus efficacy could be improved by speciation optimization. Therefore, herein we performed anti-HAdV effects of different Se speciation and found that lentinan (LNT)-decorated selenium nanoparticles (SeNPs) exhibited low cytotoxicity and excellent anti-HAdV antiviral activity. Furthermore, SeNPs@LNT reduced the HAdV infection-induced mitochondrial damage and excessive production of reactive oxygen species (ROS). It was also involved in the repair of host cell DNA damage and inhibition of viral DNA replication. SeNPs@LNT inhibited HAdV-induced apoptosis mainly by modulating the p53/Bcl-2 apoptosis signaling pathway. In vivo, SeNPs@LNT replenished Se by targeting the infected site through the circulatory system and was involved in the synthesis of Glutathione peroxidase 1 (GPx1). More importantly, GPx1 played an antioxidant and immunomodulatory role in alleviating HAdV-induced inflammatory cytokine storm and alleviating adenovirus pneumonia in Se-deficient mice. Collectively, this study provides a Se speciation of SeNPs@LNT with anti-HAdV activity, and demonstrate that SeNPs@LNT is a promising pharmaceutical candidate for the treatment of HAdV.

Naringenin-induced Oral Cancer Cell Apoptosis Via ROS-mediated Bid and Bcl-xl Signaling Pathway.

BACKGROUND: Oral cancer is a malignant tumor with a high impact and poor prognosis. Naringenin, a flavonoid found in citrus fruits and its anti-inflammatory and antioxidant properties offer potential therapeutic benefits. However, limited studies have been conducted on the impact of naringenin on human tongue carcinoma CAL-27 cells. This study aims to elucidate the correlation between naringenin and tongue cancer, thereby identifying a potential therapeutic candidate for drug intervention against tongue cancer. METHODS: The effect of naringenin on the apoptosis of CAL-27 cells and its mechanism were studied by cell counting kit-8, mitochondrial membrane potential assay with JC-1, Annexin V-- FITC apoptosis detection, cell cycle, and apoptosis analysis, Reactive Oxygen Species assay and Western blot. RESULTS: The results showed that naringenin significantly induced apoptosis in CAL-27 cells in a dose-dependent manner. Mechanistically, naringenin-induced apoptosis was mediated through the upregulation of Bid and downregulation of Bcl-xl, which led to increased generation of ROS. CONCLUSION: The findings suggested that naringenin may represent a promising candidate for the treatment of oral cancer by inducing apoptotic cell death via modulation of the Bid and Bcl-xl signaling pathways.

Selenadiazole Inhibited Adenovirus-Induced Apoptosis through the Oxidative-Damage-Mediated Bcl-2/Stat 3/NF-κB Signaling Pathway.

Human adenovirus type 7 (HAdV7) infection causes severe pneumonia, yet there are still no breakthroughs in treatment options for adenovirus, and the road to antiviral drug development faces major challenges. We attempted to find new drugs and we stumbled upon one: selenadiazole. Selenadiazole has been shown to have significant anti-tumor effects due to its unique chemical structure and drug activity. However, its effectiveness against viruses has not been evaluated yet. In our study, selenadiazole also showed superior antiviral activity. In vitro experiments, selenadiazole was able to inhibit adenovirus-mediated mitochondrial-oxidative-damage-related apoptosis, and in in vivo experiments, selenadiazole was able to inhibit apoptosis by modulating the apoptotic signaling pathway Bcl-2/Stat3/NF-κB, etc., and was able to largely attenuate adenovirus-infection-induced pneumonia and lung injury in mice. This study aims to describe a new antiviral treatment option from the perspective of anti-adenovirus-mediated oxidative stress and its associated apoptosis and to provide theoretical guidance for the treatment of clinical adenovirus infection to a certain extent.

Carambolaside W Inhibited H1N1 Influenza Virus-Induced Oxidative Stress through STAT-3/BCL-XL Signaling Pathway.

The H1N1 influenza virus is highly infectious and pathogenic, and in recent years, it has often presented seasonal mass outbreaks of infection. People infected with H1N1 will develop a high fever and other respiratory infection symptoms. If not treated in time, complications such as pneumonia may occur. In this study, we focused on developing drugs that can effectively fight against with H1N1 virus. A flavonoid glycoside was extracted from the carambola, then characterized by HR-ESI-MS with the molecular formula C47H58O2, and named carambolaside W. The flavonoid glycosides were found to have good anti-H1N1 influenza virus effects. In this study, we verified that carambolaside W has low toxicity and can effectively inhibit influenza virus replication in vitro. H1N1 virus infection induces intracellular oxidative stress damage to accelerate disease progression. The results showed that carambolaside W effectively inhibited the oxidative stress caused by H1N1 infection. The Western blot assay also revealed that carambolaside W alters the expression of apoptosis-related proteins in vitro and exerts a good anti-H1N1 influenza virus effect. In summary, carambolaside W is a low-toxicity natural flavonoid that can effectively treat the H1N1 influenza virus as a potential anti-H1N1 virus agent.

Selenium Nanoparticles Control H1N1 Virus by Inhibiting Inflammatory Response and Cell Apoptosis.

The treatment of influenza caused by H1N1 has been the focus of much attention. Selenium nanoparticles (SeNPs) have been used in many aspects of research in the last two decades. They have shown excellent performance in antiviral, anti-inflammatory, and antioxidant functions. Previous anti-H1N1 cell experiments using SeNPs have shown that they have evident antiviral effects and low toxicities. This study focuses on the mechanism of selenium nanoparticles against an H1N1 influenza virus infection in vivo. The results showed that the selenium levels in the body decreased after an H1N1 virus infection, and inflammatory factors in the lung tissues increased abnormally, leading to the onset and aggravation of an inflammatory response. The H1N1 virus infection also led to the excessive activation of apoptotic pathways in the body and induced the apoptosis of tissue cells. In addition, this study found that SeNPs can alleviate this phenomenon. All results showed that SeNPs are promising inhibitors for controlling influenza H1N1 virus infections.

Naringenin Induces HepG2 Cell Apoptosis via ROS-Mediated JAK-2/STAT-3 Signaling Pathways.

Hepatocarcinoma is one of the most prevalent digestive system tumors worldwide and lacks effective therapy. Recently, naringenin has been isolated from some citrus fruits, and its anticancer effects have been tested. However, the molecular mechanisms of naringenin and the potential implications of oxidative stress in naringenin-induced cytotoxicity in HepG2 cells remain elusive. Based on the above, the present study examined the effect of naringenin on the cytotoxic and anticancer mechanisms of HepG2 cells. Naringenin-induced HepG2 cell apoptosis was confirmed via the accumulation of the sub-G1 cell population, phosphatidylserine exposure, mitochondrial transmembrane potential loss, DNA fragmentation, caspase-3 activation, and caspase-9 activation. Furthermore, naringenin enhanced cytotoxic effects on HepG2 cells and triggered intracellular reactive oxygen species; the signaling pathways of JAK-2/STAT-3 were inhibited, and caspase-3 was activated to advance cell apoptosis. These results suggest that naringenin plays an important role in inducing apoptosis in HepG2 cells and that naringenin may be a promising candidate for cancer therapy.

Inhibition of HAdV-14 induced apoptosis by selenocystine through ROS-mediated PARP and p53 signaling pathways.

BACKGROUND: Human Adenovirus (HAdV) can cause severe respiratory symptoms in people with low immunity and there is no targeted treatment for adenovirus infection. Anti-adenoviral drugs have high clinical significance for inhibiting adenovirus infection. Selenium (Se) plays an important role in anti-oxidation, redox signal transduction, and redox homeostasis. The excellent biological activity of Se is mainly achieved by being converted into selenocystine (SeC). Se participates in the active sites of various selenoproteins in the form of SeC. The ability of SeC to resist the virus has raised high awareness due to its unique antioxidative activity in recent years. The antiviral ability of the SeC was determined by detecting the infection rate of the virus in the cells. METHODS: The experiment mainly investigated the antiviral mechanism of SeC by locating the virus in the cell, detecting the generation of ROS, observing the DNA status of the cell, and monitoring the mitochondrial membrane potential. RESULTS: In the present study, SeC was designed to resist A549 cells infections caused by HAdV-14. SeC could prevent HAdV-14 from causing cell apoptosis-related to DNA damage. SeC significantly inhibited ROS generation and protect the cells from oxidative damage induced by ROS against HAdV-14. SeC induced the increase of antiviral cytokines such as IL-6 and IL-8 by activating the Jak2 signaling pathway, and repaired DNA lesions by suppressing ATR, p53, and PARP signaling pathways. CONCLUSION: SeC might provide an effective selenium species with antiviral properties for the therapies against HAdV-14.

Selenium-ruthenium complex blocks H1N1 influenza virus-induced cell damage by activating GPx1/TrxR1.

Background: Influenza A (H1N1) virus is an acute respiratory infectious disease that causes massive morbidity and mortality worldwide. As an essential trace element, selenium is widely applied in the treatment of various diseases because of its functions of enhancing immune response, antioxidant and antiviral mutation. In this study, we constructed the selenium-containing metal complex drug delivery system Ru(biim)(PhenSe)2 (RuSe), and investigated the anti-influenza virus efficacy and the potential antiviral mechanism for RuSe. Methods: The inhibitory effect of RuSe on influenza-mediated apoptosis was examined by cell count assay, cell cycle assay, Annenxin-V assay, TUNEL-DAPI assay and reactive oxygen species level determination. Virulence assay, PCR and neuraminidase inhibition assay revealed the inhibition of RuSe on influenza virus. At the level of animal experiments, two animal models were used to clarify the role of RuSe through HE staining, immunohistochemical staining, cytokine determination, selenium metabolism determination and selenium protein expression level determination. Results: The results of this study confirm that RuSe enhances the expression levels of selenium proteins GPx1 and TrxR1 by regulating selenium metabolism, thereby inhibiting viral replication and assembly and regulating virus-mediated mitochondria-related apoptosis. On the other hand, animal experiments show that RuSe can reduce lung tissue inflammation and inhibit lung tissue cell apoptosis in mice, and improve the survival state of mice. In addition, RuSe significantly improves the low immune response of Se-deficient mice by regulating selenium metabolism, and effectively alleviated lung fibrosis and lung tissue apoptosis in Se-deficient mice. Conclusions: This study suggests that RuSe provides a promising new approach for the clinical treatment of influenza virus.

Inhibition of H3N2 Influenza Virus Induced Apoptosis by Selenium Nanoparticles with Chitosan through ROS-Mediated Signaling Pathways.

In recent years, nanotechnology has received more and more attention in the antiviral field. Among them, selenium nanoparticles (SeNPs) have received a lot of attention. Chitosan, as a substance with antiviral effect, is limited by water solubility, low bioavailability, and poor stability. In this study, the combination of SeNPs with chitosan (Se@CS) showed less toxic and good anti-H3N2 infection effect. CCK-8 and RT-PCR showed that Se@CS effectively prevented H3N2 infection of MDCK cells by inhibiting viral replication and preventing cell fragmentation and cell aggregation. In addition, Se@CS can inhibit the excessive production of ROS and the change of mitochondrial membrane potential. More importantly, Se@CS can inhibit the late apoptosis of cells caused by virus, which may be related to the inhibition of apoptotic proteins in the ROS/JNK apoptotic signaling pathway. Finally, Se@CS was also found to inhibit H3N2-induced inflammation and alleviate infection. These results prove that Se@CS is a promising inhibitor for controlling influenza H3N2 virus infection.

Inhibition of H1N1 by Picochlorum sp. 122 via AKT and p53 signaling pathways.

Influenza viruses cause a severe threat to global health, which can lead to annual epidemics and cause pandemics occasionally. However, the number of anti-influenza therapeutic agents is very limited. Polysaccharides, extracted from Picochlorum sp. (PPE), seaweed Polysaccharides, have exhibited antiviral activity and were expected to be used for influenza treatment. In our research, the capability of PPE to inhibit H1N1 infection was proved in MDCK cells. PPE could make MDCK cells avoid being infected with H1N1 and inhibited nuclear fragmentation and condensation of chromatin. PPE evidently inhibited the generation of reactive oxygen species in MDCK cells. Mechanism study revealed that PPE prevented MDCK cells from H1N1 infection through induction of apoptosis by stimulating AKT signaling pathway and suppressing p-p53 signaling pathway. In conclusion, PPE turns out to act as a prospective antiviral drug for H1N1 influenza.

Ebselen inhibits enterovirus A71-induced apoptosis through reactive oxygen species-mediated signaling pathway.

BACKGROUND: Enterovirus A71 (EV-A71)is a prevalent infection in severe hand, foot and mouth disease HFMD and can induce acute central nervous system seizures. The three EV-A71 vaccines now circulating in the market are produced for a single subtype. While EV-A71 is constantly evolving and the vaccine's efficacy is gradually reducing, no specialized anti-EV-A71 medication has yet been developed. Therefore, it is crucial to consistently develop new anti-EV-A71 medications. METHOD: Ebselen, an organoselenium molecule with glutathione oxidase-like activity, is resistant to a range of viruses. In this investigation, we used the Cell counting kit-8 (CCK-8 kit) assay in a Vero cell model to confirm the effectiveness of ebselen against EV-A71 infection. Later, to examine ebselen's anti-EV-A71 mechanism, we measured the apoptosis level of cells in different treatment groups through Annexin V, JC-1, and cell cycle assays, as well as the intracellular reactive oxygen species (ROS) concentration. Ebselen may have an impact on the apoptotic signaling pathway caused by EV-A71 infection, according to the results of a caspase-3 activity experiment. RESULT: The results showed that Ebselen protected cell damage from ROS generation, decreased the frequency of EV-A71-induced apoptosis, and inhibited caspase-3-mediated apoptosis by lowering caspase-3 activity. CONCLUSION: To summarize, ebselen is a promising anti-EV-A71 medication.

Epigallocatechin-3-gallate Induced HepG2 Cells Apoptosis through ROSmediated AKT /JNK and p53 Signaling Pathway.

BACKGROUND: Hepatocarcinoma is the third leading cause of cancer-related deaths around the world. Recently, some studies have reported that Epigallocatechin-3-gallate (EGCG) may have the anti-cancer potential. However, the affection and putative mechanisms of cytotoxicity induced by EGCG in HepG2 cells remain unknown. Based on the above, the present study evaluated the effect of EGCG on the cytotoxic and anti-cancer mechanisms of HepG2 cells. METHODS: The effect of EGCG on the apoptosis of Hep-G2 cells and its mechanism were studied by cell counting kit-8, mitochondrial membrane potential assay with JC-1, Annexin V-FITC apoptosis detection, cell cycle, and apoptosis analysis, one step TUNEL apoptosis assay, caspase 3 activity assay, caspase 9 activity Assay, Reactive Oxygen Species assay, and Western blot. RESULTS: EGCG-induced HepG2 cell apoptosis was confirmed by accumulation of the sub-G1 cells population, translocation of phosphatidylserine, depletion of mitochondrial membrane potential, DNA fragmentation, caspase-3 activation, caspase-9 activation, and poly (ADP-ribose) polymerase cleavage. Furthermore, EGCG enhanced cytotoxic effects on HepG2 cells and triggered intracellular reactive oxygen species; the signaling pathways of AKT, JNK, and p53 were activated to advance cell apoptosis. CONCLUSION: The results reveal that EGCG may provide useful information on EGCG-induced HepG2 cell apoptosis and be an appropriate candidate for cancer chemotherapy.

Inhibition of H1N1 Influenza Virus-induced Apoptosis by Ebselen Through ROS-mediated ATM/ATR Signaling Pathways.

Influenza A viruses can cause global outbreaks and seasonal pandemics. However, the use of conventional anti-influenza drugs leads to an increase in drug-resistant mutations in influenza viruses worldwide. Therefore, numerous studies have focused on developing effective anti-influenza drugs. It is feasible to treat influenza by targeting influenza-mediated oxidative damage. Ebselen is a synthetic organoselenium compound which provides glutathione peroxidase-like activity. It has been shown to play a role in anti-influenza therapy, but the mechanism remains to be further explored. This experiment verified the anti-influenza effect of ebselen. CCK-8 and PCR showed that ebselen had a significant inhibitory effect on virus replication compared with the virus group. In addition, the mechanistic investigations revealed that ebselen could inhibit influenza-mediated apoptosis, mitochondrial damage, accumulation of reactive oxygen species, and DNA breakage. At the same time, ebselen significantly inhibited the phosphorylation of ATM and ATR and promoted the activation of PARP and Caspase-3. Ebselen, on the other hand, reduced the inflammatory response caused by influenza. These results suggest that ebselen is a promising inhibitor for H1N1.

L-Selenocysteine induced HepG-2 cells apoptosis through reactive oxygen species-mediated signaling pathway.

BACKGROUND: Currently, Liver cancer is the fifth most common tumor and the second most important reason for cancer-related death in the world. However, there are still many limitations of the clinical treatment of liver cancer, and new treatment options are clearly needed. Fortunately, studies have shown that L-Selenocysteine has a certain effect on cancer. This study was to investigate the effects of L-Selenocysteine on the inhibition of cell proliferation and the promotion of apoptosis of HepG-2 cells through ROS mediated fine signaling pathway. MATERIALS AND METHODS: CCK-8 assay was applied to evaluating the cytotoxic effect of L-Selenocysteine on HepG-2 cells. Electron microscopy, flow cytometry and Western Blot was utilization in further researching cells signaling pathways. RESULTS: The growth of HepG-2 cells was inhibited by L-selenocysteine ​​treatment in a dose-dependent manner. The cell viability decreased to 52.20%, 43.20% and 30.83% under the treatment of 4, 8, 16 µM L-selenocysteine, respectively. L-Selenocysteine had higher cytotoxicity towards HepG-2 cells than normal cells. L-Selenocysteine can induce the apoptosis of HepG-2 cells by increasing the DNA fragmentation, and activating the Caspase-3. In addition, it was found that the mechanism of the induction to HepG-2 cell apoptosis by L-Selenocysteine was closely related to the overproduction of ROS and promoted apoptosis through the Bcl-2 signaling pathway. CONCLUSIONS: Our data suggest that L-selenocysteine ​​may cause mitochondrial damage and subsequently stimulate ROS production. ROS can damage cellular DNA and mediate the production of Casapase-8, Bid, Bcl-2 and other proteins, affecting downstream signaling pathways, and ultimately induced apoptosis.

Selenium nanoparticles inhibited H1N1 influenza virus-induced apoptosis by ROS-mediated signaling pathways.

Influenza A (H1N1) viruses are distributed around the world and pose a threat to public health. Vaccination is the main treatment strategy to prevent influenza infection, but antiviral drugs also play an important role in controlling seasonal and pandemic influenza. Currently, as influenza viruses may be developing antiviral resistance, new agents with different modes of action are being investigated. Recently, selenium nanoparticles (SeNPs), which have antiviral effects, have attracted increasing attention in biomedical interventions. The appearance of nanotechnology has attracted great attention in the field of nanomedicine. SeNPs constitute an attractive vector platform for delivering a variety of drugs to action targets. SeNPs are being explored for potential therapeutic efficacy in a variety of oxidative stress and inflammation-mediated diseases, such as cancer, arthritis, diabetes, and kidney disease. SeNPs could inhibit infection of Madin-Darby canine kidney (MDCK) cells with H1N1 and prevent chromatin condensation and DNA fragmentation. ROS play a key role in physiological processes for apoptosis. SeNPs significantly inhibited the production of reactive oxygen species (ROS) in MDCK cells. Mechanistic investigation revealed that SeNPs inhibited the apoptosis induced by H1N1 virus infection in MDCK cells by improving the level of GPx1. Our results suggest that SeNPs are an effective selenium source and a promising H1N1 influenza antiviral candidate.

Duvira Antarctic polysaccharide inhibited H1N1 influenza virus-induced apoptosis through ROS mediated ERK and STAT-3 signaling pathway.

BACKGROUND: The H1N1 influenza virus causes acute respiratory tract infection, and its clinical symptoms are very similar to those of ordinary influenza. The disease develops rapidly. If the flu is not treated, complications such as pneumonia, respiratory failure, and multiple organ damage can occur, resulting in a high fatality rate. Influenza virus mutates rapidly. At present, there is no specific drug for H1N1, so it is an urgent need for clinical care to find new drugs to treat H1N1. MATERIALS AND METHODS: The polysaccharide derived from Durvillaea Antarctica green algae has a certain antiviral effect. In this study, the results of CCK-8, apoptosis cycle detection, JC-1 and Western blotting proved that Duvira Antarctic polysaccharide (DAPP) has the ability to inhibit H1N1 infection. RESULTS: CCK-8 test showed that the DAPP with concentration at 32 µg/mL had no toxicity to MDCK cells. In addition, DAPP reduced cell apoptosis by inhibiting the ERK signaling pathway. Meanwhile, DAPP could increase the expression of STAT3 and significantly inhibited proinflammatory cytokines. CONCLUSIONS: In summary, these results suggested that DAPP may be potential with the ability to resist the H1N1 influenza virus.

Changes of Host Immunity Mediated by IFN-γ+ CD8+ T Cells in Children with Adenovirus Pneumonia in Different Severity of Illness.

The host immunity of patients with adenovirus pneumonia in different severity of illness is unclear. This study compared the routine laboratory tests and the host immunity of human adenovirus (HAdV) patients with different severity of illness. A co-cultured cell model in vitro was established to verify the T cell response in vitro. Among 140 patients with confirmed HAdV of varying severity, the number of lymphocytes in the severe patients was significantly reduced to 1.91 × 109/L compared with the healthy control (3.92 × 109/L) and the mild patients (4.27 × 109/L). The levels of IL-6, IL-10, and IFN-γ in patients with adenovirus pneumonia were significantly elevated with the severity of the disease. Compared with the healthy control (20.82%) and the stable patients (33.96%), the percentage of CD8+ T cells that produced IFN-γ increased to 56.27% in the progressing patients. Adenovirus infection increased the percentage of CD8+ T and CD4+ T cells that produce IFN-γ in the co-culture system. The hyperfunction of IFN-γ+ CD8+ T cells might be related to the severity of adenovirus infection. The in vitro co-culture cell model could also provide a usable cellular model for subsequent experiments.

Inhibition of enterovirus 71 infection by polysaccharides extracted from Picochlorum sp. 122 via the AKT and ATM/ATR signaling pathways.

Enterovirus 71 (EV71) poses a major threat to public health globally due to severe and even fatal hand, foot, and mouth disease (HFMD). However, no effective antiviral agents are available to treat HFMD caused by this virus. Polysaccharides have been shown to exhibit antiviral activity, and polysaccharides extracted from Picochlorum sp. 122 (PPE) could potentially be used to treat HFMD, but reports on their antiviral activity are limited. In this study, the antiviral activity of PPE against EV71 was verified in Vero cells. PPE was shown to limit EV71 infection, as demonstrated using an MTT assay and by observing the cellular cytopathic effect. In addition, a decrease in VP1 RNA and protein levels indicated that PPE effectively inhibits proliferation of EV71 in Vero cells. An annexin V affinity assay also indicated that PPE protects host cells from apoptosis through the AKT and ATM/ATR signalling pathways. These results demonstrate that PPE has potential as an antiviral drug to treat HFMD caused by EV71.