Intestinal metabolites participate in various physiological processes, including energy metabolism, cell-to-cell communication, and host immunity. These metabolites mainly originate from gut microbiota and hosts. Although many host metabolites are dominant in intestines, such as free fatty acids, amino acids and vitamins, the metabolites derived from gut microbiota are also essential for intestinal homeostasis. In addition, some metabolites are only generated and released by gut microbiota, such as bacteriocins, short-chain fatty acids, and quorum-sensing autoinducers. In this review, we summarize recent studies regarding the crosstalk between pathogens and metabolites from different sources, including the influence on bacterial development and the activation/inhibition of immune responses of hosts. All of these functions would affect the colonization of and infection by pathogens. This review provides clear ideas and directions for further exploring the regulatory mechanisms and effects of metabolites on pathogens.
Hepatitis B surface antigen (HBsAg) and Hepatitis B surface antibody (anti-HBs) were reported simultaneously among Hepatitis B virus (HBV) infections. HBsAg is a specific indicator of acute or chronic HBV infections, while anti-HBs is a protective antibody reflecting the recovery and immunity of hosts. HBsAg and anti-HBs coexist during seroconversion and then form immune complex, which is rare detected in clinical cases. However, with the promotion of vaccination and the application of various antiviral drugs, along with the rapid development of medical technology, the coexistence of HBsAg and anti-HBs has become more prevalent. Mutations in the viral genomes, immune status and genetic factors of hosts may contribute to the coexistence. Novel HBsAg assays, with higher sensitivity and ability to detect mutations or immune complexes, can also yield HBsAg/anti-HBs coexistence. The discovery of coexistence has shattered the idea of traditional serological patterns and raised questions about the effectiveness of vaccines. Worth noting is that HBsAg/anti-HBs double positivity is strongly associated with progressive liver diseases, especially hepatocellular carcinoma. In conclusion, viral mutations, host factors, and methodology impacts can all lead to the coexistence of HBsAg and anti-HBs. This coexistence is not an indicator of improvement, as an increased risk of adverse clinical outcomes still exists.
Reactive oxidative species (ROS) are important inflammatory mediators. Electrons escaping from the mitochondrial electron transport chain (ETC) during oxidative phosphorylation (OXPHOS) in the mitochondrial respiratory chain (RC) complexes contribute to ROS production. The cellular antioxidant enzymes are important for maintaining ROS release at the physiological levels. It has been reported that BoHV-1 infection induces overproduction of ROS and oxidative mitochondrial dysfunction in cell cultures. In this study, we found that chemical interruption of RC complexes by TTFA (an inhibitor of RC complex II), NaN3 (an inhibitor of RC complex IV), and oligomycin A (an inhibitor of ATP synthase) consistently decreased virus productive infection, suggesting that the integral processes of RC complexes are important for the virus replication. The virus infection significantly increased the expression of subunit SDHB (succinate dehydrogenase) and MTCO1 (cytochrome c oxidase subunit I), critical components of RC complexes II and IV, respectively. The expression of antioxidant enzymes including superoxide dismutase 1 (SOD1), SOD2, catalase (CAT), and glutathione peroxidase 4 (GPX4) was differentially affected following the virus infection. The protein TFAM (transcription factor A, mitochondrial) stimulated by either nuclear respiratory factor 1 (NRF1) or NRF2 is a key regulator of mitochondrial biogenesis. Interestingly, the virus infection at the late stage (at 16 h after infection) stimulated TFAM expression but decreased the levels of both NRF1 and NRF2, indicating that virus infection activated TFAM signaling independent of either NRF1 or NRF2. Overall, this study provided evidence that BoHV-1 infection altered the expression of molecules associated with RC complexes, antioxidant enzymes, and mitochondrial biogenesis-related signaling NRF1/NRF2/TFAM, which correlated with the previous report that virus infection induces ROS overproduction and mitochondrial dysfunction.
Serological tests have been widely used for detecting human T-cell lymphotropic virus type 1/2 (HTLV-1/2) antibodies in the endemic areas, but their performance in low-risk populations is rarely reported. The aim of this study was to evaluate the performance of four HTLV-1/2 screening assays and to discuss a strategy for diagnosis of HTLV-1/2 infection in a non-endemic area. At the present study, 1546 specimens repeatedly reactive (RR) by one screening ELISA were collected from blood centers/banks from January 2016 to April 2019. Avioq-ELISA, Murex-ELISA, Roche-ECLIA and Fujirebio-CLIA were independently performed on each plasma sample and compared to WB and LIA confirmatory tests. Positive or indeterminate specimens with blood available were quantified by qPCR. The results showed that 48 samples were finally confirmed as HTLV-1 positive, 13 were HTLV positive, 151 were indeterminate, and 387 were negative. All the WB-positive samples were also LIA-positive. Roche-ECLIA showed the highest sensitivity that was able to detect 91.8% positives and combined with the Murex-ELISA would significantly increase the positive detection rate (98.4%). In addition, LIA yield more indeterminate and HTLV-untyped results than WB (152 vs. 27), but was able to resolve infection status of some individuals with an indeterminate WB. Besides, 3 WB indeterminate and 1 LIA-untyped samples were confirmed as HTLV-1 positive by qPCR. Based on these findings, we put forward a proper test strategy for HTLV-1/2 diagnosis in low-prevalence areas. If possible, the Roche-ECLIA with the highest sensitivity is suggested as a second screening assay in primary labs. If not, all RR specimens are recommended to be firstly retested by Roche-ECLIA and Murex-ELISA in the reference lab. Secondly, samples reactive to any one of the two tests were quantified by qPCR, and then the NAT-negatives were furtherly submitted to LIA for confirmation. Thereby, the cost can be reduced and the diagnostic accuracy would be improved.
Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection. Evidence of OBI clinical relevance is emerging but the mechanisms of its occurrence remain unclear. In this study, the molecular characteristics of 97 confirmed OBI from Chinese blood donors were analyzed and relevant mutations were identified. Recombinant HBsAg bearing these mutations were expressed in vitro and the antigenicity and HBsAg secretion properties were analyzed. Results showed that 45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences were identified. Two groups of mutations in the S gene were significantly associated with OBI. The first group included mutations creating new N-linked glycosylation sites at positions s116, s123, s130, and s131 + s133 or removing the existing one at s146. Mutations TCT123-125NCT/NFT were associated with reduced antigenicity, while TST116-118NST, GTS130-132NTS, and TSM131-133NSS/NYT/NST were associated with varying levels of impaired HBsAg secretion. N146 mutations had no effect on HBsAg production pattern. The second group included substitutions within the S transmembrane domains TMD1-3. Only mutations C85R, L87R, L88R, and C90R within TMD2 were associated with defective HBsAg production. These mutations appear to be rare and mostly strain specific but they may contribute to the multifactorial occurrence of OBI.
Bovine herpesvirus 1 (BoHV-1) is an important pathogen of cattle that causes lesions in mucosal surfaces, genital tracts and nervous systems. As a novel oncolytic virus, BoHV-1 infects and kills numerous human tumor cells. However, the mechanisms underlying the virus-induced cell damages are not fully understood. In this study, we demonstrated that virus infection of MDBK cells induced high levels of DNA damage, because the percentage of comet tail DNA (tailDNA%) determined by comet assay, a direct indicator of DNA damage, and the levels of 8-hydroxyguanine (8-oxoG) production, an oxidative DNA damage marker, consistently increased following the virus infection. The expression of 8-oxoguanine DNA glycosylase (OGG-1), an enzyme responsible for the excision of 8-oxoG, was significantly decreased due to the virus infection, which corroborated with the finding that BoHV-1 infection stimulated 8-oxoG production. Furthermore, the virus replication in human tumor cells such as in A549 cells and U2OS cells also induced DNA damage. Chemical inhibition of reactive oxidative species (ROS) production by either ROS scavenger N-Acetyl-l-cysteine or NOX inhibitor diphenylene iodonium (DPI) significantly decreased the levels of tailDNA%, suggesting the involvement of ROS in the virus induced DNA lesions. Collectively, these results indicated that BoHV-1 infection of these cells elicits oxidative DNA damages, providing a perspective in understanding the mechanisms by which the virus induces cell death in both native host cells and human tumor cells.
Background Demographic characteristic surveillance of transfusion-transmitted infections (TTIs) among blood donors is crucial to formulating control strategies and preventing TTIs. This study aimed to investigate the demographic characteristics and social factors associated with TTIs among blood donors from 14 different blood centers or banks in China, covering almost the entire China. Methods Demographic information of 1976 blood donations were obtained from the donor databases of 14 blood centers. The results of the samples were confirmed by the National Center for Clinical Laboratories (NCCL). Results Of the 1976 donations, 928 were confirmed as TTI positive (HBV, 309; HCV, 162; HIV, 116; syphilis, 341), while 1048 tested negative. The differences in demographic distribution of TTI positive and negative donations regarding age, previous donation history, occupation, and education were statistically significant ( p < 0.001). The factors mentioned above and marital status had associations with TTIs. Among the TTIs, only syphilis was related to ethnicity (adjusted odds ratio [aOR]: 2.309, 95% confidence interval [CI]: 1.378–3.868, p = 0.001), and only HBV positivity was not associated with marital status (HBV, aOR: 0.933, 95% CI: 0.670–1.299, p = 0.681). Gender and education were independent predictors of HIV and syphilis infections ( p < 0.05). Conclusions Demographic characteristics in this study included age, gender, previous donation history, ethnicity, marital status, occupation, and education, some of which were associated with TTIs. The most susceptible populations for TTIs were unmarried males and first-time donors aged between 26 and 55 years, and blood donors who were workers or company employees with low-educational level. Timely surveillance and updated demographic data on blood donors are critical for blood safety.
Background: Literature suggests that left ventricular global longitudinal strain (LV-GLS) on speckle echocardiography has the potential to predict cardiotoxicity amongst breast cancer patients receiving chemotherapy such as anthracycline, taxane, cyclophosphamide, and trastuzumab. Our study aimed to collect evidence for the prognostic value of LV-GLS for predicting chemotherapy-induced cardiotoxicity in breast cancer patients. Methods:A detailed search of the PubMed, Google Scholar, Cochrane Library, and Scopus databases was conducted for published articles up to August 31, 2022. In our meta-analysis, we looked at 13 studies with a total of 1007 breast cancer patients getting chemotherapy that looked at the predictive value of GLS.Results: Absolute GLS change during treatment showed a pooled sensitivity of 84% (95% CI 74% to 91%) and a pooled specificity of 77% (95% CI 68% to 84%). For a relative change in GLS, we observed a pooled sensitivity of 76% (95% CI 56% to 89%) and a pooled specificity of 83% (95% CI 73% to 90%). For an absolute change in GLS, we observed a positive likelihood ratio (LR), and the negative LR was 4 and .21. Summary receiver operating characteristics curve with prediction and confidence intervals represents a promising summary area under the curve (sAUC) of .88, 95% CI ranges from .85 to .91 for absolute change in GLS, as well as for relative change (sAUC, .87, 95% CI .84 to .90). Conclusion:Our results demonstrated an estimation of LV-GLS after the beginning of required chemotherapy, including anthracyclines and trastuzumab, had a promising prognostic value for predicting the likelihood of cancer therapeutics-related cardiac dysfunction. To confirm our findings, well-designed prospective adequately powered diagnostic randomised trials are necessary.
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