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1.
LP-BM5 murine leukemia virus (MuLV) induces an immunodeficiency syndrome (MAIDS) in C57BL/6 mice which resembles immunological abnormalities observed in early stages of human AIDS. In our study, MAIDS virus-infected mice were exposed to low doses of ultraviolet radiation (UVR) before and after virus inoculation and compared with MAIDS-infected but not UVR-exposed mice. In all tested parameters (blood IgM levels; mitogenic responses to PHA, ConA, LPS and anti-mu; MLR; antigenic response to SRBC; enlargement and histopathologic changes of the spleen) we observed the same trend: changes due to MAIDS infection were more pronounced in the UVR-exposed group than in the unexposed group. Statistically significant differences between these two groups were seen for mitogenic responses at two different time points after virus inoculation. These results demonstrate that in vivo UVR exposure enhances the immunosuppressive effects of a retroviral infection. UVR exposure may affect the progression of AIDS in a similar manner.  相似文献   

2.
The green anole (Anolis carolinensis) is the most northerly distributed of its Neotropical genus. This lizard avoids a winter hibernation phase by the use of sun basking behaviors. Inevitably, this species is exposed to high doses of ambient solar ultraviolet radiation (UVR). Increases in terrestrial ultraviolet-B (UV-B) radiation secondary to stratospheric ozone depletion and habitat perturbation potentially place this species at risk of UVR-induced immunosuppression. Daily exposure to subinflammatory UVR (8 kJ/m2/day UV-B, 85 kJ/m2/day ultraviolet A [UV-A]), 6 days per week for 4 weeks (total cumulative doses of 192 kJ/m2 UV-B, 2.04 x 10(3) kJ/m2 UV-A) did not suppress the anole's acute or delayed type hypersensitivity (DTH) response to horseshoe crab hemocyanin. In comparison with the available literature UV-B doses as low as 0.1 and 15.9 kJ/m2 induced suppression of DTH responses in mice and humans, respectively. Exposure of anoles to UVR did not result in the inhibition of ex vivo splenocyte phagocytosis of fluorescein labeled Escherichia coli or ex vivo splenocyte nitric oxide production. Doses of UV-B ranging from 0.35 to 45 kJ/m2 have been reported to suppress murine splenic/peritoneal macrophage phagocytosis and nitric oxide production. These preliminary studies demonstrate the resistance of green anoles to UVR-induced immunosuppression. Methanol extracts of anole skin contained two peaks in the ultraviolet wavelength range that could be indicative of photoprotective substances. However, the resistance of green anoles to UVR is probably not completely attributable to absorption by UVR photoprotective substances in the skin but more likely results from a combination of other factors including absorption by the cutis and absorption and reflectance by various components of the dermis.  相似文献   

3.
Abstract The hairless mouse has been used as an experimental model for photocarcinogenesis for about 20 years. Although the carcinogenesis action spectra for mice and man are not known, acute responses to ultraviolet radiation (UVR) in the biologically active UVB and UVC region (wavelengths below 320 nm) can be compared. Vascular response (predominantly edema) action spectra for monochromatic radiation in the Skh:HR-l (albino hairless) male mouse were determined. These action spectra were found to be very similar to the human erythema action spectrum that had been developed using the same monochromator. The accuracy of this experimentally derived action spectrum was tested with a series of polychromatic source spectra. The mice were exposed to radiation from a long arc Xe lamp filtered by varying thicknesses of Schott WG320 filters, which yielded a wide range of biologically effective spectra. Spectral irradiance measurements, when weighted with the mouse edema and human erythema action spectra and multiplied by the irradiation time required to elicit a threshold response (edema), yielded a constant weighted dose regardless of irradiation spectral quality. The integrated effective dose was approximately 200 J/m2 of 297 nm equivalent energy, agreeing with requirements for the monochromatic 297 nm dose in the mice as well as for minimal human erythema. These data suggest a commonality in the UVR chromophores of mice and men as they relate to the acute responses described, and a direct additivity of effectiveness from the UVR components in a polychromatic beam, at least over the portion of the UVR spectrum tested (λ > 295 nm).  相似文献   

4.
《中国化学快报》2023,34(1):107446
Repeated waves of influenza virus H7N9 epidemics after 2013 have caused severe influenza in humans, with mortality reaching approximately 40%–50%. To prevent possible pandemics, the development of highly effective vaccines against influenza virus H7N9 is highly desired. In the present study, by taking advantage of the d-tetra-peptide adjuvant (GDFDFDY), we reported a simple method to prepare H7N9 vaccines. Naproxen (Npx), with good anti inflammatory and broad anti-viral effects, was employed as an N-terminal capping group to construct a hydrogel precursor, Npx-GDFDFDY. The hydrogel adjuvant was prepared using a routine heating cooling protocol and the final vaccine was ready after mixing with the split A/Zhejiang/DTID-ZJU01/2013 (H7N9) antigen by vortexing. Compared with the traditional Al(OH)3 adjuvant vaccine and the split vaccine, our hydrogel adjuvant vaccine showed the best preventive effects against H7N9 infection. A mechanistic study illustrated that higher antibody responses and variations in cytokine expression might account for its increased protective effects. Our strategy demonstrated the advantages of a peptide hydrogel adjuvant in the application of vaccines against H7N9 and demonstrated its potential application in vaccines against emerging threats from other viruses.  相似文献   

5.
Exposure of certain strains of mice to ultraviolet radiation (UVR) causes suppression of some innate and adaptive immune responses. One such consequence of acute UVB exposure is a reduction in the number of Langerhans cells (LC) in the epidermis and an increase in dendritic cells (DC) in lymph nodes draining the irradiated skin sites. Exposure to chronic UVB irradiation also has effects on the immune system, but it is unknown what effects are caused by repeated doses of solar simulated radiation (SSR). Consequently, the main aims of the present study were to determine whether repeated exposure to low doses of SSR would lead to similar changes in these cell populations and whether chronic doses of SSR activate a protective photoadaptation mechanism. Groups of C3H/HeN mice were irradiated daily with 3.7 J/cm(2) SSR from Cleo Natural lamps for 2, 10, 20, 30 or 60 days. Further groups of mice received an additional dose of 7.4 J/cm(2) SSR on days 2, 10, 30 or 60 to test for photoadaptation. The numbers of LC in the epidermis and DC in the lymph nodes draining irradiated skin sites were counted 24 h after the final irradiation. With the exception of mice irradiated for only 2 days, LC were significantly reduced throughout the chronic irradiation protocol, and no recovery occurred. DC numbers were significantly increased in the draining lymph nodes of mice irradiated for 20 days and 60 days.  相似文献   

6.
In the present study, the anti-influenza A (H2N2) virus activity of patchouli alcohol was studied in vitro, in vivo and in silico. The CC?? of patchouli alcohol was above 20 μM. Patchouli alcohol could inhibit influenza virus with an IC?? of 4.03 ± 0.23 μM. MTT assay showed that the inhibition by patchouli alcohol appears strongly after penetration of the virus into the cell. In the influenza mouse model, patchouli alcohol showed obvious protection against the viral infection at a dose of 5 mg/kg/day. Flexible docking and molecular dynamic simulations indicated that patchouli alcohol was bound to the neuraminidase protein of influenza virus, with an interaction energy of -40.38 kcal mol?1. The invariant key active-site residues Asp151, Arg152, Glu119, Glu276 and Tyr406 played important roles during the binding process. Based on spatial and energetic criteria, patchouli alcohol interfered with the NA functions. Results presented here suggest that patchouli alcohol possesses anti-influenza A (H2N2) virus properties, and therefore is a potential source of anti-influenza agents for the pharmaceutical industry.  相似文献   

7.
Lin S  Liu N  Yang Z  Song W  Wang P  Chen H  Lucio M  Schmitt-Kopplin P  Chen G  Cai Z 《Talanta》2010,83(1):262-268
Metabolomics is the downstream of systems biology and has drawn significant interest for studying the metabolic networks from cells to organisms. To profile the metabolites in two different cell lines (A549 and AGS) infected with influenza A virus, gas chromatography coupled with mass spectrometry (GC/MS) was employed. Some differentiating metabolites in the cell lines were tentatively identified using reference library, interpreted and visualized by applying principal components analysis (PCA) and cluster heat map. Consequently, metabolic flux profiling allowed the differentiation of fatty acid biosynthesis and cholesterol metabolism during viral replication in the cell lines. The change in fatty acid turnover was also observed. Metabolomics investigation also revealed the different responses between A549 and AGS cell lines to the virus infection. From the pattern recognition results, AGS cell line might be more susceptible to influenza A virus. Regarding the fact that AGS is a poorly differentiated gastric adenocarcinoma cell line whereas A549 is a relatively differentiated lung tumor one, it is speculated that viral replication might be associated with the cell differentiations.  相似文献   

8.
EFFECT OF UV IRRADIATION ON LETHAL INFECTION OF MICE WITH Candida albicans   总被引:1,自引:0,他引:1  
Exposure of mice to UV radiation inhibits the induction and elicitation of the delayed-type hypersensitivity (DTH) response to Candida albicans. To determine whether UV irradiation also affects the pathogenesis of systemic C. albicans infection, C3H mice were exposed to a single dose of 48 kJ/m2 UV-B radiation from FS40 sunlamps 5 days before or 5 days after sensitization with formalin-fixed C. albicans and challenged intravenously (i.v.) with a lethal dose of viable fungi 6 days after sensitization (11 or 1 days after UV irradiation). Exposing unsensitized mice to UV radiation 11 days before lethal challenge had no effect on survival, but the survival time of mice exposed to UV radiation 1 day before challenge was reduced by more than 50%. In the latter group, decreased survival time correlated with persistence of C. albicans in the brain and progressive growth of C. albicans in the kidneys. Sensitization of unirradiated mice with formalin-fixed C. albicans extended their survival time following lethal i.v. challenge with viable C. albicans. Exposing the mice to UV radiation 5 days before sensitization did not abrogate this beneficial effect of sensitization on survival, even though it significantly reduced the DTH response. Thus, immunity to systemic infection did not depend on the ability of the mice to exhibit a DTH response to C. albicans. The beneficial effect of sensitization on survival after lethal infection was abrogated, however, in mice exposed to UV radiation 1 day before lethal challenge with C. albicans. Furthermore, these mice were unable to contain the progressive growth of C. albicuns in the kidneys, in contrast to sensitized, unirradiated mice. The induction of cutaneous inflammation with turpentine had no effect on the survival rate of mice lethally infected with C. albicans, suggesting that inflammation alone is not sufficient to decrease the survival time of C. albicans-infected mice.  相似文献   

9.
Replication-incompetent adenoviruses expressing three major glycoproteins (gB, gC, and gD) of pseudorabies virus (PrV) were constructed and used to examine the ability of these glycoproteins to induce protective immunity against a lethal challenge. Among three constructs, recombinant adenovirus expressing gB (rAd-gB) was found to induce the most potent immunity biased to Th1-type, as determined by the IgG isotype ratio and the profile of the Th1/Th2 cytokine production. Conversely, the gC-expressing adenovirus (rAd-gC) revealed Th2-type immunity and the gD-expressing adenovirus (rAd-gD) induced lower levels of IFN-γ and IL-4 production than other constructs, except IL-2 production. Mucosal delivery of rAd-gB induced mucosal IgA and serum IgG responses and biased toward Th2-type immune responses. However, these effects were not observed in response to systemic delivery of rAd-gB. In addition, rAd-gB appeared to induce effective protective immunity against a virulent viral infection, regardless of whether it was administered via the muscular or systemic route. These results suggest that administration of replication-incompetent adenoviruses can induce different types of immunity depending on the expressed antigen and that recombinant adenoviruses expressing gB induced the most potent Th1-biased humoral and cellular immunity and provided effective protection against PrV infection.  相似文献   

10.
Abstract— UV-induced alkaline labile viral DNA damage was detected following irradiation of adenovirus type 2 and found to be repaired following the infection of human KB cells. Human adenovirus type 2 was irradiated with various doses of UV and subsequently used to infect human KB cells in tissue culture at approximately 2 × 103 particles per cell. Before, and at various times after infection, the viral DNA was examined on alkaline sucrose gradients. Irradiated free virus DNA showed a dose dependent decrease in molecular weight compared to unirradiated virus DNA, indicating the presence of UV-induced alkaline labile lesions. Furthermore, an increase in the molecular weight of the irradiated virus DNA was found after infection indicating that alkaline labile lesions were removed from the viral DNA by a host mediated repair mechanism. After infection, the molecular weight of the irradiated virus DNA reached a value similar to that of unirradiated virus DNA for all the UV doses studied.  相似文献   

11.
Ultraviolet radiation (UVR) is known to suppress immune responses in human subjects. The purpose of this study was to develop dose responses across a broad range of skin pigmentation in order to facilitate risk assessment. UVR was administered using FS 20 bulbs. Skin pigmentation and UVR sensitivity were evaluated using Fitzpatrick classifications, minimal erythemal dose (MED), slope of the erythemal dose response curve (sED), baseline pigmentation and tanning response. To assess immune responses dinitrochlorobenzene (DNCB) was applied to irradiated buttock skin 72 h after irradiation. Two weeks later DNCB was applied to the inside upper arm. Skin thickness was measured before and after challenge. Dose response was modeled (to obtain a regression line) for the entire group of 185 subjects. With the exception of sED none of the above-mentioned pigmentation indicators contributed significantly to variability around the regression line. Thus, differences in sensitivity for multiple skin types based on Fitzpatrick classification or MED were not observed. However, differences in immune sensitivity to UVR were detected between subjects with steep erythemal dose response curves and those with moderate or flat responses. For subjects with steep erythemal responses the dose calculated to suppress the immune response by 50% was 114 mJ/cm2. This group included individuals with Fitzpatrick skin types I-V, MED for these subjects ranged from 30 to 80 mJ/cm2. The 50% suppression dose for subjects with weak or no erythemal response could not be computed (the dose response was flat). This resistant group included subjects with skin types IV-VI and MED for these subjects ranged from 41 to > 105 mJ/cm2. This study provides a human dose response for UVR suppression of contact sensitivity that will be useful in risk assessment. It is the first study to provide this information using the FS sun lamp and is the first study to include people of color. The sED appears to be a new variable for identifying sensitive subjects at risk of UVR-induced immune suppression.  相似文献   

12.
Melanoma incidence is increasing, with poor prognosis cases growing faster in California Hispanics than in non-Hispanic whites. Ultraviolet Radiation (UVR) exposure as a child has been found to disproportionately increase the risk of melanoma. To determine correlates of UVR exposure in this high-risk population, we conducted a study in predominately Hispanic 4th and 5th grade classrooms in Los Angeles County, a high UVR environment, during the spring. To address potential reporting bias, electronic UV dosimeters were utilized to objectively measure the association between UVR exposure and constructs (acculturation, sun protective behavior and knowledge, family interventions) obtained on baseline questionnaires (n = 125). Tanning attitude (wanting to get a tan) was associated with lower median time spent outside (1.73 min versus 22.17, AUC 82.08, Sensitivity 0.78, Specificity 0.73) and standard erythemal dose (SED) on weekends, but positively associated with sun protective knowledge. Sun protective knowledge and family discussion of sunscreen were also inversely associated with objectively measured time outside. Students spent a median 30.61 (IQR 19.88) minutes outside per day (SED 0.30, IQR 0.20), with only 35.70% of it occurring in nonschool hours. We determined the majority of UVR exposure in this population occurs at school, providing valuable guidance for future interventions.  相似文献   

13.
Little is known about the validity of self-recorded sun exposure and time spent outdoors for epidemiological research. The aims of the current study were to assess how well participants' self-recorded time outdoors compared to objective measurements of personal UVR doses. We enrolled 124 volunteers aged 40 and above who were identified from targeted subgroups of US radiologic technologists. Each volunteer was instructed to wear a polysulfone (PS) dosimeter to measure UVR on their left shoulder and to complete a daily activity diary, listing all activities undertaken in each 30 min interval between 9:00 A.M. and 5:00 P.M. during a 7 day period. In a linear regression model, self-recorded daily time spent outdoors was associated with an increase of 8.2% (95% CI: 7.3-9.2%) in the personal UVR exposure with every hour spent outdoors. The amount of self-recorded total daily time spent outdoors was better correlated with the personal daily UVR dose for activities conducted near noon time compared to activities conducted in the morning or late afternoon, and for activities often performed in the sun (e.g. gardening or recreation activities) compared to other outdoor activities (e.g. driving) in which the participant is usually shaded from the sun. Our results demonstrated a significant correlation between diary records of time spent outdoors with objective personal UVR dose measurements.  相似文献   

14.
PHOTOINACTIVATION OF INFLUENZA VIRUS FUSION AND INFECTIVITY BY ROSE BENGAL   总被引:1,自引:0,他引:1  
Rose bengal inactivated influenza virus upon exposure to light. Infectivity and fusion were inactivated with the same dose dependence, supporting the suggestion that the virucidal activity of photodynamic agents against enveloped viruses may be generally due to inactivation of their fusion protein(s). Concentrations required for inac-ti vation were found to depend upon the ratio of rose bengal to virus, rather than on the nominal aqueous concentration. Fusion-competent virosomes were inactivated similarly to intact virus particles. The HAZ portion of the influenza fusion protein HA underwent two different, apparently mutually exclusive modifications upon illumination with rose bengal: cross-linking, and conversion to a form that moved slightly more slowly on sodium dodecyl sulfate poly-acrylamide gel electrophoresis. Inactivation of viral fusion was inhibited by oxygen removal or addition of azide or β-carotene, and was enhanced by D2O, consistent with partial involvement of singlet oxygen. The possibility of a second mechanism of viral photoinactivation, by direct interaction between the viral fusion protein and the pho-toactivated dye, is also discussed.  相似文献   

15.
Abstract— Exposure of skin to UV radiation can cause diverse biological effects, including induction of inflammation, alteration in cutaneous immune cells and impairment of contact hypersensitivity (CHS) responses. Our laboratory has demonstrated that oral feeding as well as topical application of a poly-phenolic fraction isolated from green tea (GTP) affords protection against the carcinogenic effects of UVB (280–320 nm) radiation. In this study, we investigated whether GTP could protect against UVB-induced immunosuppression and cutaneous inflammatory responses in C3H mice. Immunosuppression was assessed by contact sensitization with 2,4-dinitrofluorobenzene applied to UVB-irradiated skin (local suppression) or to a distant site (systemic suppression), while double skin-fold swelling was used as the measure of UVB-induced inflammation. Topical application of GTP (1–6 mg/animal), 30 min prior to or 30 min after exposure to a single dose of UVB (2 kj/m2) resulted in significant protection against local (25–90%) and systemic suppression (23–95%) of CHS and inflammation in mouse dorsal skin (70–80%). These protective effects were dependent on the dose of GTP employed; increasing the dose (1–6 mg/animal) resulted in an increased protective effect (25–93%). The protective effects were also dependent on the dose of UVB (2–32 kJ/m2). Among the four major epicatechin derivatives present in GTP, (‐)-epigallocatechin-3-gallate, the major constituent in GTP, was found to be the most effective in affording protection against UVB-caused CHS and inflammatory responses. Our study suggests that green tea, specifically polyphenols present therein, may be useful against inflammatory dermatoses and immunosuppression caused by solar radiation.  相似文献   

16.
These studies addressed the hypothesis that UV radiation (UVR) could affect immune responses in mice infected with Borrelia burgdorferi. Immunity against the Lyme spirochete B. burgdorferi was studied in a murine model of UV-induced immune suppression. Borrelia-specific cellular and humoral responses were examined following immunosuppressive doses of UVR. Low-passage Borrelia were injected intradermally at the base of the tail following irradiation. At various time points after infection the blood was cultured for the presence of Borrelia and the serum analyzed for Borrelia-specific antibodies. Two weeks after infection one hind-limb joint was cultured for the presence of spirochetes and the contralateral joint was examined histologically for arthritis formation. The results demonstrated that UV irradiation, administered at the site of infection or at a distant site, suppressed Borrelia-specific cellular and humoral responses in infected mice. Suppression of delayed-type hypersensitivity and antibody responses to UV was abrogated by administration of anti-interleukin (IL)-10 after UV irradiation. In addition, UV irradiation altered the dissemination pattern of the bacteria from the skin into the blood and exacerbated arthritis when compared with unirradiated controls. From these studies we concluded that UV irradiation can modulate the immune response to Borrelia and exacerbate the subsequent arthritic component of Lyme disease in mice. Furthermore, our studies suggest that IL-10 is in part responsible for the suppression of both cellular and humoral responses in addition to playing a role in the development of Lyme arthritis.  相似文献   

17.
Antiviral Effect of Matrine against Human Enterovirus 71   总被引:1,自引:0,他引:1  
Human enterovirus 71, a member of the Picornaviridae family, is one of the major causative agent of hand, foot and mouth disease in children less than six years old. This illness has caused mortalities in large-scale outbreaks in the Asia-Pacific region in recent years. No vaccine or antiviral therapy is available. In this study, antiviral effect of matrine against enterovirus 71 were evaluated in vitro and in vivo. Matrine could suppress the viral RNA copy number on rhabdomyosarcoma cells. Moreover, matrine treatment of mice challenged with a lethal dose of enterovirus 71 reduced the mortality and relieved clinical symptoms. The results showed that matrine may represent a potential therapeutic agent for enterovirus 71 infection.  相似文献   

18.
The development of highly immunodeficient mouse strains has allowed the reconstitution of functional human immune system components in mice. New-generation humanized mice generated in this manner have been extensively used for modeling viral infections that are exclusively human tropic. Epstein–Barr virus (EBV)-infected humanized mice reproduce cardinal features of EBV-associated B-cell lymphoproliferative disease and EBV-associated hemophagocytic lymphohistiocytosis (HLH). Erosive arthritis morphologically resembling rheumatoid arthritis (RA) has also been recapitulated in these mice. Low-dose EBV infection of humanized mice results in asymptomatic, persistent infection. Innate immune responses involving natural killer cells, EBV-specific adaptive T-cell responses restricted by human major histocompatibility and EBV-specific antibody responses are also elicited in humanized mice. EBV-associated T-/natural killer cell lymphoproliferative disease, by contrast, can be reproduced in a distinct mouse xenograft model. In this review, recent findings on the recapitulation of human EBV infection and pathogenesis in these mouse models, as well as their application to preclinical studies of experimental anti-EBV therapies, are described.  相似文献   

19.
20.
This study reports 5 years of (1998-2003) data on continuous solar-irradiation measurements from a scanning spectroradiometer (SUV-100) in Valdivia, Chile (39 degrees S), accompanied by evaluation of the impact of ultraviolet radiation (UVR) on marine macroalgae of this site. UVR conditions showed a strong seasonal variation, which was less pronounced toward longer wavelengths. Daily maximum dose rates (clear days) averaged in winter-summer: UV-B(290-315 nm) 0.30-2.1, UV-B(290-320 nm) 0.70-3.7, UV-A(315-400 nm) 20.6-62.1, UV-A(320-400 nm) 20.2-60.5 W m(-2), and photosynthetically active radiation (PAR) 969-2423 micromol m(-2) s(-1). The corresponding daily doses (all the days) ranged: UV-B(290-315 nm) 2.6-40.7, UV-B(290-320 nm) 6.7-78.5, UV-A(315-400 nm) 228-1539, UV-A(320-400 nm) 224-1501, and PAR 2008-13308 kJ m(-2) d(-1). Taking into consideration action spectra of a biological interest, the risk of UV exposure could be up to 37 times higher in summer than in winter. The photosynthetic activity (as maximum quantum yield of chlorophyll fluorescence, F(v)/F(m)) of the brown alga Lessonia nigrescens from the infralittoral zone was markedly more sensitive to UVR than of the green alga Enteromorpha intestinalis from the upper midlittoral, and the UV-B wave band increased markedly photoinhibition. In L. nigrescens, maximal photoinhibition (40%) took place at weighted (the action spectrum for photoinhibition of photosynthesis) UVR doses of 800 kJ m(-2), irrespective of the season (corresponding midsummer daily dose in Valdivia is 480 kJ m(-2)). In winter, when this alga was at its most sensitive, the weighted UV dose causing 35-40% photoinhibition was around 200 kJ m(-2). In E. intestinalis, weighted doses of 800 kJ m(-2) resulted in low photoinhibition (<10 %) and no clear seasonal patterns could be inferred. These results confirm that midday summer levels of UV-B and their daily doses in southern Chile are high enough to produce stress to intertidal macroalgae.  相似文献   

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