PMID: 

Arch Virol. 2013 Apr ;158(4):799-807. Epub 2012 Nov 28. PMID: 23188495

Abstract Title: 

Antiviral effects of a probiotic Enterococcus faecium strain against transmissible gastroenteritis coronavirus.

Abstract: 

The enteropathogenic coronavirus transmissible gastroenteritis virus (TGEV) causes severe disease in young piglets. We have studied the protective effects of the probiotic Enterococcus faecium NCIMB 10415 (E. faecium), which is approved as a feed additive in the European Union, against TGEV infection. E. faecium was added to swine testicle (ST) cells before, concomitantly with, or after TGEV infection. Viability assays revealed that E. faecium led to a dose-dependent rescue of viability of TGEV-infected cells reaching nearly to complete protection. Virus yields of the E. faecium-treated cultures were reduced by up to three log10 units. Western blot analysis of purified TGEV revealed that the levels of all viral structural proteins were reduced after E. faecium treatment. Using transmission electron microscopy, we observed attachment of TGEV particles to the surface of E. faecium which might be a means to trap virus and to prevent infection. Increased production of nitric oxide in the cells treated with E. faecium and elevated expression of interleukin 6 and 8 pointed to stimulated cellular defense as a mechanism to fight TGEV infection.

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PMID: 

Nat Prod Commun. 2012 Nov ;7(11):1415-7. PMID: 23285797

Abstract Title: 

Anti-human coronavirus (anti-HCoV) triterpenoids from the leaves of Euphorbia neriifolia.

Abstract: 

Euphorbia neriifolia L. is a spiny herb native to Southeast Asia and currently cultivated in southern Taiwan. From the ethanolic extract of E. neriifolia leaves, 23 compounds were isolated, including 22 triterpenoids and one flavonoid glycoside. The anti-human coronavirus (HCoV) activity of the separated triterpenoids was studied revealing the structure-activity relationship (SAR) of these isolates. 3beta-Friedelanol exhibited more potent anti-viral activity than the positive control, actinomycin D, which implies the importance of the friedelane skeleton as a potential scaffold for developing new anti-HCoV-229E drugs.

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PMID: 

BMC Vet Res. 2014 Jan 16 ;10:24. Epub 2014 Jan 16. PMID: 24433341

Abstract Title: 

Sambucus nigra extracts inhibit infectious bronchitis virus at an early point during replication.

Abstract: 

BACKGROUND: Infectious bronchitis virus (IBV) is a pathogenic chicken coronavirus. Currently, vaccination against IBV is only partially protective; therefore, better preventions and treatments are needed. Plants produce antimicrobial secondary compounds, which may be a source for novel anti-viral drugs. Non-cytotoxic, crude ethanol extracts of Rhodiola rosea roots, Nigella sativa seeds, and Sambucus nigra fruit were tested for anti-IBV activity, since these safe, widely used plant tissues contain polyphenol derivatives that inhibit other viruses.RESULTS: Dose-response cytotoxicity curves on Vero cells using trypan blue staining determined the highest non-cytotoxic concentrations of each plant extract. To screen for IBV inhibition, cells and virus were pretreated with extracts, followed by infection in the presence of extract. Viral cytopathic effect was assessed visually following an additional 24 h incubation with extract. Cells and supernatants were harvested separately and virus titers were quantified by plaque assay. Variations of this screening protocol determined the effects of a number of shortened S. nigra extract treatments. Finally, S. nigra extract-treated virions were visualizedby transmission electron microscopy with negative staining.Virus titers from infected cells treated with R. rosea and N. sativa extracts were not substantially different from infected cells treated with solvent alone. However, treatment with S. nigra extracts reduced virus titers by four orders ofmagnitude at a multiplicity of infection (MOI) of 1 in a dose-responsive manner. Infection at a low MOI reduced viral titers by six orders of magnitude and pretreatment of virus was necessary, but not sufficient, for full virus inhibition. Electron microscopy of virions treated with S. nigra extractshowed compromised envelopes and the presence of membrane vesicles, which suggested a mechanism of action.CONCLUSIONS: These results demonstrate that S. nigra extract can inhibit IBV at an early point in infection, probably by rendering the virus non-infectious. They also suggest that future studies using S. nigra extract to treat or prevent IBV or other coronaviruses are warranted.

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PMID: 

Planta Med. 2014 Feb ;80(2-3):177-82. Epub 2014 Jan 23. PMID: 24458263

Abstract Title: 

Kaempferol derivatives as antiviral drugs against the 3a channel protein of coronavirus.

Abstract: 

The protein coded by the open-reading-frame 3a of SARS coronavirus has been demonstrated to form a cation-selective channel that may become expressed in the infected cell. The activity of the channel is involved in the mechanism of virus release. Drugs that inhibit the ion channel can, therefore, inhibit virus release, and they could be a source for development of novel therapeutic antiviral agents. Various drugs found in Chinese herbs that are well known as anticancer agents also have an antiviral potency. Here we tested the flavonols kaempferol, kaempferol glycosides, and acylated kaempferol glucoside derivatives with respect to their potency to block the 3a channel. We used the Xenopus oocyte with a heterologously expressed 3a protein as a model system to test the efficacy of the flavonols. Some of these drugs turned out to be potent inhibitors of the 3a channel. The most effective one was the glycoside juglanin (carrying an arabinose residue) with an IC50 value of 2.3 µM for inhibition of the 3a-mediated current. Kaempferol derivatives with rhamnose residue also seem to be quite effective. We suggest that viral ion channels, in general, may be a good target for the development of antiviral agents, and that, in particular, kaempferol glycosides are good candidates for 3a channel proteins of coronaviruses.

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PMID: 

BMC Vet Res. 2014 Mar 28 ;10:75. Epub 2014 Mar 28. PMID: 24673930

Abstract Title: 

High-dose dietary zinc oxide mitigates infection with transmissible gastroenteritis virus in piglets.

Abstract: 

BACKGROUND: Zinc (Zn) supplementation has been shown to reduce the incidence of diarrhea and to protect animals from intestinal diseases, but the mechanisms of this protective effect against virus infection in vivo have not yet been elucidated. Transmissible gastroenteritis virus (TGEV) causes diarrhea in piglets with an age-dependent decrease of severity.RESULTS: We used 60 weaned piglets that were divided into three groups to evaluate the effect of different Zn levels added to a conventional diet (50 mg Zn/kg diet, Znlow, control group). The other groups received the diet supplemented with ZnO at final concentrations of 150 mg Zn/kg diet (Znmed), or 2,500 mg/kg diet (Znhigh). Oral challenge infection with TGEV was performed when the pigs had been fed for 1 week with the respective diet. Half of the piglets of each group were sacrificed at day 1 and 18 after challenge infection. Fecal consistency was improved and body weights increased in the Znhigh group when compared to the other groups, but no direct effect of Zn concentrations in the diet on fecal TGEV shedding and mucosal immune responses was detectable. However, in the Znhigh group, we found a prevention of villus atrophy and decreased caspase-3-mediated apoptosis of jejunal epithelium. Furthermore, pigs receiving high Zn diet showed a down-regulation of interferon (IFN)-α, oligoadenylate synthetase (OAS), Zn transporter SLC39A4 (ZIP4), but up-regulation of metallothionein-1 (MT1), as well as the Zn transporters SLC30A1 (ZnT1) and SLC30A5 (ZnT5). In addition, forskolin-induced chloride secretion and epithelial resistance were controlled at a physiological level inthe Znhigh but not the other groups. Finally, in the Znhigh group, we documented an earlier and higher systemic TGEV-specific serum antibody response.CONCLUSIONS: These results suggest that high dietary Zn could provide enhanced protection in the intestinal tract and stimulate the systemic humoral immune response against TGEV infection.

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PMID: 

Virus Res. 2015 Jan 2 ;195:148-52. Epub 2014 Oct 6. PMID: 25300802

Abstract Title: 

Porcine epidemic diarrhea virus infection: inhibition by polysaccharide from Ginkgo biloba exocarp and mode of its action.

Abstract: 

Porcine epidemic diarrhea virus (PEDV) is the predominant cause of severe entero-pathogenic diarrhea in swine. Until now there is no recorded clinically effective antiviral chemotherapeutic agent for treatment of diseases caused by PEDV. This study aimed to investigate in vitro anti-PEDV effect of polysaccharide from Ginkgo biloba exocarp and mode of its action. The polysaccharide exhibited potent antiviral activity against PEDV reducing the formation of a visible CPE [a 50% inhibitory concentration (IC50)=1.7±1.3μg/mL], compared to positive control, ribavirin and it did not show cytotoxicity at 100μg/mL [a 50% cytotoxicity concentration (CC50)=100μg/mL]. Polysaccharide also showed effective inhibitory effects when added at the viral attachment and entry steps. Moreover, polysaccharide effectively inactivated PEDV infection in time-, dose- and temperature-dependent manners. Overall, this research revealed that polysaccharide could inhibit PEDV infection, and that polysaccharide may be involved in PEDV-Vero cell interactions, as the virus attachment and entry to the Vero cells was hindered by the polysaccharide. Therefore, polysaccharide possessing effective inhibitory effect on viral attachment and entry steps of PEDV life cycle is a good candidate for development of antivirals.

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PMID: 

Animal. 2015 Sep ;9(9):1473-80. Epub 2015 May 22. PMID: 25998982

Abstract Title: 

Improved performance and immunological responses as the result of dietary genistein supplementation of broiler chicks.

Abstract: 

The present study aimed to investigate the effect of supplemental genistein (an isoflavonoid) on performance, lymphoid organs' development, and cellular and humoral immune responses in broiler chicks. A total of 675-day-old male broiler chicks (Ross 308) were randomly assigned to the five replicate pens (15 chicks each) of nine experimental diets. Dietary treatments included a negative (not-supplemented) control diet, two positive control groups (virginiamycin or zinc-bacitracin, 20 mg/kg), and diets containing 10, 20, 40, 80, 160 and 320 mg/kg of genistein. The cutaneous basophil hypersensivity (CBH) test was measured at day 10 of age after toe web injection with phytohemagglutinin-P. In addition, sera samples were collected after different antigen inoculations to investigate antibody responses. At day 28 of age, three randomly selected birds from each pen were euthanized to evaluate the relative weights of lymphoid organs. Results showed that dietary supplementation of both antibiotics increased (P

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PMID: 

Int J Behav Med. 2017 02 ;24(1):25-41. PMID: 27307013

Abstract Title: 

Efficacy of Biofeedback in Chronic back Pain: a Meta-Analysis.

Abstract: 

PURPOSE: The aims of the present analysis were to investigate the short- and long-term efficacy and treatment moderators of biofeedback as a psychological treatment option for chronic back pain.METHOD: A literature search using PubMed, PsycINFO, and the Cochrane Library identified 21 eligible studies including 23 treatment conditions and 1062 patients.RESULTS: Meta-analytic integration resulted in a significant small-to-medium effect size for pain intensity reduction (Hedges' g = 0.60; 95 % confidence interval (CI) 0.44, 0.76) that proved to be stable with a significant small-to-large effect size (Hedges' g = 0.62; 95 % CI 0.40, 0.84) over an average follow-up phase of 8 months. Biofeedback also proved to be effective in reducing depression (Hedges' g = 0.40; 95 % CI 0.27, 0.52), disability (Hedges' g = 0.49; 95 % CI 0.34, 0.74), reduction of muscle tension (EMG; Hedges' g = 0.44; 95 % CI 0.22, 0.65), and improving cognitive coping (Hedges' g = 0.41; 95 % CI 0.26, 0.57). These effects remained comparatively stable at follow-up and for controlled studies only. Moderator analyses revealed longer biofeedback treatments to be more effective for reducing disability and a greater proportion of biofeedback in the treatment to be more effective for reducing depression. Publication bias analyses demonstrated the consistency of these effects.CONCLUSION: It is concluded that biofeedback treatment can lead to improvements on various pain-related outcomes in the short and long terms, both as a standalone and as an adjunctive intervention.

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PMID: 

Adv Clin Exp Med. 2019 Nov ;28(11):1477-1483. PMID: 30968613

Abstract Title: 

The effectiveness of whole-body cryotherapy and physical exercises on the psychological well-being of patients with multiple sclerosis: A comparative analysis.

Abstract: 

BACKGROUND: Due to the chronic character of multiple sclerosis (MS), non-pharmacological treatment can be applied. These therapies can be a good complementation to standard pharmacological treatment.OBJECTIVES: The aim of the study was to evaluate the effectiveness of whole-body cryotherapy (WBC) and physical exercise training on the psychological and general well-being of patients with MS.MATERIAL AND METHODS: The study was carried out on 60 patients, who were divided into 3 groups: cryotherapy (Cryo), physical exercise training (Gym) and cryotherapy with physical exercise training (CryoGym). The Psychological General Well-Being Index, the Hospital Anxiety and Depression Scale and the Rivermead Mobility Index were used at 2 points in time: T1 – before the first therapy session and T2 – after 14 days of therapy.RESULTS: Statistically significant differences in the psychosocial well-being were found in the Gym and CryoGym group. Reduction of depressive symptoms and improved functional status was noted in Cryo group. The most significant improvement was observed in the group using WBC with exercise training (CryoGym).CONCLUSIONS: Whole-body cryotherapy with physical exercise training was an effective therapy for patients with MS. The introduction of WBC into the standard physiotherapy protocol for patients with MS is fully justified.

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PMID: 

Support Care Cancer. 2019 Dec 14. Epub 2019 Dec 14. PMID: 31836937

Abstract Title: 

Systematic review of oral cryotherapy for the management of oral mucositis in cancer patients and clinical practice guidelines.

Abstract: 

PURPOSE: To update the 2013 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) clinical practice guidelines on oral cryotherapy for the management of oral mucositis (OM) caused by cancer therapies.METHODS: A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The evidence for each intervention for specific cancer treatment modalities was assigned a level of evidence (LoE). The findings were added to the database used to develop the 2013 MASCC/ISOO clinical practice guidelines. Based on the LoE, the guidelines were set as: recommendation, suggestion, or no guideline possible.RESULTS: A total of 114 papers were identified: 44 from PubMed and 70 from Web of Science. After abstract triage and merging with the 2013 database, 36 papers were reviewed. The LoE for prevention of OM with oral cryotherapy in patients undergoing autologous hematopoietic stem cell transplant using high-dose melphalan conditioning protocols was upgraded, and the guideline changed to recommendation. Additionally, the recommendation for prevention of OM with oral cryotherapy in patients receiving bolus 5-fluorouracil for the treatment of solid tumors was confirmed. No guidelines were possible for other clinical settings.CONCLUSIONS: The evidence supports recommendations for the use of oral cryotherapy for the prevention of OM for either (i) patients undergoing autologous hematopoietic stem cell transplant with high-dose melphalan conditioning protocols or (ii) patients receiving bolus 5-fluorouracil chemotherapy.

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