Inactivated Sendai Virus Induces Apoptosis in Murine Melanoma Cells by IGF-1R Down-regulation

The mortality of cancer patients has considerably improved due to progress in surgery, chemotherapy and radiotherapy. However, some types of cancers, such as melanoma, remain refractory to conventional strategies. Although melanoma accounts for only 4% of all dermatological malignancies, it is responsible for 80% of mortalities from skin tumors[11. The reported survival rate of melanoma over 5 years is not yet encouraging due to its chemo-resistance and rapid metastasis. Therefore, it is necessary to develop new drugs with potent activity and weak side-effect against melanoma.

Inactivated Sendai Virus Induces ROS-dependent Apoptosis and Autophagy in Human Prostate Cancer Cells

Objective The current study aims to investigate the effect of Hemagglutinating virus of Japan envelope（HVJ-E） on induction of apoptosis and autophagy in human prostate cancer PC3 cells, and the underlying mechanisms. Methods PC3 cells were treated with HVJ-E at various multiplicity of infection（MOI）, and the generated reactive oxygen species（ROS）, cell viability, apoptosis, and autophagy were detected, respectively. Next, the role of ROS played in the regulation of HVJ-E-induced apoptosis and autuphagy in PC3 cells were analysed. In the end, the relationship between HVJ-E-induced apoptosis and autuophagy was investigated by using rapamycin and chloroquine. Results Flow cytometry assay revealed that HVJ-E treatment induced dose-dependent apoptosis and that the JNK and p38 MAPK signaling pathways were involved in HVJ-E-induced apoptosis in PC3 cells. In addition, HVJ-E was able to induce autophagy in PC3 cells via the class III PI3 K/beclin-1 pathway. The data also implyed that HVJ-E-triggered autophagy and apoptosis were ROS dependent. When ROS was blocked with N-acetylcysteine（NAC）, HVJ-E-induced LC3-II conversion and apoptosis were reversed. Interestingly, HVJ-E-induced apoptosis was significantly increased by an inducer of autophagy, rapamycin pretreatment, both in vitro and in vivo. Conclusion HVJ-E exerts anticancer effects via autophagic cell death in prostate cancer cells.

Inactivated Sendai Virus Induces Apoptosis Mediated by Reactive Oxygen Species in Murine Melanoma Cells

Objective This paper aims to investigate the apoptotic effect of inactivated Sendai virus （hemagglutinating virus of Japan-enveloped, HVJ-E） on routine melanoma cells （B16FlO） and the possible mechanisms involved in the putative apoptotic reactions. Methods B16F10 cells were treated with HVJ-E at various multiplicities of infection （MOI）, and the reactive oxygen species （ROS）, cell viability, and apoptosis were measured. Next, the roles of ROS in the regulation of Bcl-2/Bax and the activation of mitogen-activated protein kinase （MAPK） pathways in HVJ-E-treated B16F10 cells were analyzed. To further evaluate the cytotoxic effect of HVJ-E-generated ROS on B16FlO cells, HVJ-E was intratumorally injected, both with and without N-acetyI-L-cysteine （NAC）, into melanoma tumors on BALB/c mice. Tumor volume was then monitored for 3 weeks, and the tumor proteins were separated for immunoblot assay. Results Treatment of B16F10 cells with HVJ-E resulted in a dose-dependent inhibition of cell-viability and an induction of apoptosis. The latter effect was associated with the generation of ROS. Inhibition of ROS generation by NAC resulted in a significant reduction of HVJ-E-induced Erkl/2, JNK, and p38 MAPK activation. Additionally, ROS inhibition caused a decrease in the Bcl-2/Bax ratio as well as promoting activation of apoptosis both in vitro and in vivo. Conclusion These results suggest that HVJ-E possesses potential anticancer activity in B16F10 cells through ROS-mediated mitochondrial dysfunction involving the MAPK pathway.

Induction of Apoptosis in Hormone-resistant Human Prostate Cancer PC3 Cells by Inactivated Sendai Virus

Objective Inactivated Sendai virus particle [hemagglutinating virus of Japan envelope （HVJ-E）] has a potential oncolytic effect due to its ability to induce apoptosis in tumor cells. However, the molecular mechanism of apoptosis induction in cancer cells mediated by HVJ-E has not been fully elucidated. This paper aims to investigate the underlying mechanism of apoptosis induction by HVJ-E in prostate cancer cells （PC3）. Methods PC3 cells were treated with HVJ-E at various MOI, and then interferon-β（IFN-β） production, and the cell viability and apoptosis were detected by ELISA, MTl--based assay and flow cytometry, respectively. Next, the roles of Jak-Stat, MAPK and Akt pathways played in HVJ-E-induced apoptosis in PC3 cells were analyzed by immunoblot assay. To further evaluate the cytotoxic effect of HVJ-E on PC3 cells, HVJ-E was intratumorally injected into prostate cancers on BALB/c-nude mice, and the tumor volume was monitored for 36 days. Results HVJ-E induced iFN-β production and activated Jak-Stat signaling pathway, which resulted in the activation of caspase-8, caspase-3, and PARP in PC3 prostate cancer cells post HVJ-E treatment. Furthermore, we observed for the first time that p38 and Jnk MAPKs in PC3 cells contributed to HVJ-E-induced apoptosis. In addition, intratumoral HVJ-E treatment displayed a direct inhibitory effect in an in vivo BALB/c nude mouse prostate cancer model. Conclusion Our findings have provided novel insights into the underlying mechanisms by which HVJ-E induces apoptosis in tumor cells.

Testing of the Adhesion of Herpes Simplex Virus on Textile Substrates and Its Inactivation by Household Laundry Processes

Viral infections like Herpes simplex increasingly pose a serious threat to European health care systems and welfare of the population. Indirect transmission routes of infections via inanimate surfaces are often underestimated. In this study, we investigated the adhesion and persistence of Herpes simplex virus on cotton fabrics as well as its inactivation by domestic laundry. Virus adhesion to textile fibers was distinct, because viral DNA was detectable on fabrics for at least 48 hours after contamination as well as after home laundry. Particles remained infectious for several hours at room temperature and partially for 48 hours at 2℃ - 8℃. Nevertheless, domestic laundry was able to inactivate virus particles given that detergents were adequately used. This confirmed that standard household laundry processes, as established in Europe, are a suitable tool to reduce infectious Herpes virus particles from textiles, thereby supporting the prevention of infections circulating in the household and community.

Nitric-oxide enriched plasma-activated water inactivates 229E coronavirus and alters antiviral response genes in human lung host cells

The ongoing pandemic caused by the novel coronavirus,SARS-CoV-2,is influencing global health.Moreover,there is a major threat of future coronaviruses affecting the entire world in a similar,or even more dreadful,manner.Therefore,effective and biocompatible therapeutic options against coronaviruses are urgently needed.To address this challenge,medical specialists require a well-informed and safe approach to treating human coronaviruses(HCoVs).Herein,an environmental friendly approach for viral inactivation,based on plasma technology,was considered.A microwave plasma system was employed for the generation of the high amount of gaseous nitric oxide to prepare nitric oxide enriched plasma-activated water(NO-PAW),the effects of which on coronaviruses,have not been reported to date.To determine these effects,alpha-HCoV-229E was used in an experimental model.We found that NO-PAW treatment effectively inhibited coronavirus infection in host lung cells,visualized by evaluating the cytopathic effect and expression level of spike proteins.Interestingly,NO-PAW showed minimal toxicity towards lung host cells,suggesting its potential for therapeutic application.Moreover,this new approach resulted in viral inactivation and greatly improved the gene levels involved in host antiviral responses.Together,our findings provide evidence of an initiation point for further progress toward the clinical development of antiviral treatments,including such coronaviruses.

Effect of ultrasound with methylene blue as sound sensitive agent on virus inactivation

The goal of this paper is to explore a method for virus inactivation based on ultrasonic treatment,and on this basis,to explore the synergistic effect of methylene blue as a sonosensitizer in virus inactivation.The titer of human parainfluenza virus type 3(HPIV3),Autographacaliforinica nuclear polyhedrosis virus carried a green fluorescent reporter gene(AcNPV-GFP)and Enterovirus group D 68(EV-D68)were determined by plaque assays or TCID50 methods after treatment by MB combined with illumination(MB photochemical,MBP)or ultrasonic excitation.Different ultrasonic power and time,MB concentration gradient were set to determine the best antiviral combination.For the enveloped virus HPIV3 and AcNPV-GFP,pure ultrasonic or MBP treatment could reduce viral titer more than 104,and ultrasonic combined with MB could completely inactivate HPIV3 and AcNPV-GFP in 5min while traditional MBP methods could only reduce viral titer about 10X.For the nonenveloped virus EV-D68,pure ultrasonic or MBP treatment only reduced the viral titer about 102,but ultrasonic combined with MB treatment could reduce the viral titer about 103 in 5min and completely inactive EV-D68 in 10min(reduced 105).Compared with MBP method and pure ultrasonic inactivation,ultrasonic combined with MB has better inactivation effect on either enveloped or non-enveloped viruses,and the appropriate combination of parameters is expected to be a new blood transfusion transmitted virus inactivation method.

Vaccines’ Safety and Effectiveness in the Midst of Covid-19 Mutations

We examined the coronavirus classification and evolution through its multiple mutations that have increased its transmissibility rate up to 70% globally, threatening to undermine the promise of a number of emerging vaccines that primarily focus on the immune detection of the Spike trimer. The safety and effectiveness of different vaccination methods are evaluated and compared, including the mRNA version, the Adenovirus DNA, Spike protein subunits, the deactivated virus genres, and the live attenuated coronavirus. Mutations have been long considered as random events, or mistakes during the viral RNA replication. Usually, what can go wrong will go wrong;therefore, repeated transformations lead to the extinction of a virus. On the contrary, the aggregate result of over 300,000 Covid-19 variants has expanded its transmissibility and infectiousness. Covid-19 mutations do not degrade the virus;they empower and facilitate its disguise to evade detection. Unlike other coronaviruses, Covid-19 amino acid switches do not reflect the random unfolding of errors that eventually eradicate the virus. Covid-19 appears to use mutations adaptively in the service of its survival and expansion. We cite evidence that Covid-19 inhibits the interferon type I production, compromising adaptive immunity from recognizing the virus. The deleterious consequences of the cytokine storm where the CD8+ killer cells injure the vital organs of the host may well be a Covid-19 manoeuvring to escape exposure. It is probable that evolution has programmed Covid-19 with an adeptness designed to debilitate key systemic defences to secure its subsistence. To date the infectiousness of the Covid-19 pandemic is exponentially increasing, denoting the possibility of an even more dangerously elusive, inconspicuous, and sophisticated version of the disease.

Seasonal Effect of Sunlight on COVID-19 among Countries with and without Lock-Downs

Objective: The main aim of the study was to determine whether COVID-19 epidemiological data reported by countries in different hemispheres correlated with the seasons of the year. Since stay-at-home orders could be a main factor affecting the time individuals spent outdoors, the progression of COVID-19 in countries that mandated the most stringent lock-downs and stay-at-home orders was compared to countries in the same hemisphere that did not order their citizens to remain at home. Methods: Infections attributed to COVID-19 per million inhabitants, deaths per infections × 100, and deaths per million inhabitants from different countries were analyzed utilizing national reports registered in the Johns’ Hopkins database together with the most recent world population data. The null hypothesis (no difference between countries with and without lock-downs) was tested (two tailed test, p < 0.01) for each paired set of data according to well established statistical analysis. Results: The shift of highest infection rates from countries in the northern-towards countries in the southern-hemisphere during early 2020 and the reverse in December of the same year correlates with the seasonal variation in the flux of germicidal sunlight. Mortality rate for the same virus among different countries did not show a seasonal component. COVID-19 infection mortality rate was considerably lower in developing countries of South America (11 of the largest countries) than in several (at least 8) developed European countries. Discussion: COVID-19 resulted in higher infections during winter than in summer. The finding of a seasonal component, correlating the progression of the pandemic with local solar flux, demonstrates that infectious virus in the environment plays a role in the pandemic since direct person-to-person transmission would afford little time for solar inactivation. Similar epidemiological data amongst “locked” and “unlocked” countries demonstrates that lock-downs and similar confining measures had no effect on the chances of healthy individuals becoming infected with SARS-CoV-2 or dying of COVID-19.

Covid-19 Mutations and the Effect of Different Vaccines on Immune Memory

We traced the coronavirus classification and evolution,analyzed the Covid-19 composition and its distinguishing characteristics when compared to SARS-CoV and MERS-CoV.Despite their close kinship,SARS-CoV and Covid-19 display significant structural differences,including 380 amino acid substitutions,and variable homology between certain open reading frames that are bound to diversify the pathogenesis and virulence of the two viral compounds.A single amino acid substitution such as replacing Aspartate(D)with Glycine(G)composes the D614G mutation that is around 20%more infectious than its predecessor 614D.The B117 variant,that exhibits a 70%transmissibility rate,harbours 23 mutants,each reflecting one amino acid exchange.We examined several globally spreading mutations,501.V2,B1351,P1,and others,with respect to the specific amino acid conversions involved.Unlike previous versions of coronavirus,where random mutations eventually precipitate extinction,the multiplicity of over 300,000 mutations appears to have rendered Covid-19 more contagious,facilitating its ability to evade detection,thus challenging the effectiveness of a large variety of emerging vaccines.Vaccination enhances immune memory and intelligence to combat or obstruct viral entry by generating antibodies that will prohibit the cellular binding and fusion with the Spike protein,restricting the virus from releasing its contents into the cell.Developing antibodies during the innate response,appears to be the most compelling solution in light of the hypothesis that Covid-19 inhibits the production of Interferon type I,compromising adaptive efficiency to recognize the virus,possibly provoking a cytokine storm that injures vital organs.With respect to that perspective,the potential safety and effectiveness of different vaccines are evaluated and compared,including the Spike protein mRNA version,the Adenovirus DNA,Spike protein subunits,the deactivated virus genres,or,finally,the live attenuated coronavirus that appears to demonstrate the greatest effectiveness,yet,encompass a relatively higher risk.

From Monovalent to Multivalent Vaccines, the Exploration for Potential Preventive Strategies Against Hand, Foot, and Mouth Disease(HFMD)

Hand,foot,and mouth disease(HFMD)recently emerged as a global public threat.The licensure of inactivated enterovirus A71(EV-A71)vaccine was the first step in using a vaccine to control HFMD.New challenges arise from changes in the pathogen spectrum while vaccines directed against other common serotypes are in the preclinical stage.The mission of a broad-spectrum prevention strategy clearly favors multivalent vaccines.The development of multivalent vaccines was attempted via the simple combination of potent monovalent vaccines or the construction of chimeric vaccines comprised of epitopes derived from different virus serotypes.The present review summarizes recent advances in HFMD vaccine development and discusses the next steps toward a safe and effective HFMD vaccine that is capable of establishing a crossprotective antibody response.