Using SCC Antigen and CRP Levels as Prognostic Biomarkers in Recurrent Oral Cavity Squamous Cell Carcinoma

Squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) levels have been successfully used to stratify risk groups in primary oral squamous cell carcinoma (OSCC) patients; however, related biomarkers have rarely been investigated in recurrent OSCC. The purpose of the present study was to analyze the relationships of SCC-Ag and CRP levels at the time of recurrence with clinical factors and prognosis. We retrospectively recruited patients with recurrence in a cohort of 534 OSCC patients between March 2001 and July 2013. One hundred patients had recurrence. The serum SCC-Ag and CRP levels were measured at the time of cancer diagnosis, 3 to 6 months after treatment with clinical disease-free, and at the time of recurrence. The SCC-Ag levels were significantly lowered after treatment (paired t-test: p = 0.001) and re-elevated at the time of recurrence (paired t-test: p = 0.027). An SCC-Ag level ≥2.0 ng/ml and a CRP level ≥5.0 mg/L at the time of recurrence were significantly associated with recurrent tumor status (P<0.001), recurrent nodal metastasis (χ² trend test: P = 0.020), distant metastasis (P<0.001), and overall survival (P<0.001). Moreover, the influence of both elevated SCC-Ag and CRP levels on overall survival (P<0.001, H.R. [95% CI]: 5.406 [2.210–13.222]) still existed after adjusting for the recurrent tumor stage and patient age. The present study demonstrates that concurrent high levels of both SCC-Ag and CRP at the diagnosis of recurrence acts as a predictor of recurrent tumor status, recurrent advanced tumor stage, distant metastasis, and survival after the diagnosis of recurrence. This study expands the applicability of these two markers in the risk stratification in recurrent OSCC.     

Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with CAP – Results from the German competence network CAPNETZ

Background

Aim of this study was to evaluate the correlation of inflammatory markers procalcitonin (PCT), C-reactive protein (CRP) and leukocyte count (WBC) with microbiological etiology of CAP.

Methods

We enrolled 1337 patients (62 ± 18 y, 45% f) with proven CAP. Extensive microbiological workup was performed. In all patients PCT, CRP, WBC and CRB-65 score were determined. Patients were classified according to microbial diagnosis and CRB-65 score.

Results

In patients with typical bacterial CAP, levels of PCT, CRP and WBC were significantly higher compared to CAP of atypical or viral etiology. There were no significant differences in PCT, CRP and WBC in patients with atypical or viral etiology of CAP. In contrast to CRP and WBC, PCT markedly increased with severity of CAP as measured by CRB-65 score (p < 0.0001). In ROC analysis for discrimination of patients with CRB-65 scores > 1, AUC for PCT was 0.69 (95% CI 0.66 to 0.71), which was higher compared to CRP and WBC (p < 0.0001). CRB-65, PCT, CRP and WBC were higher (p < 0.0001) in hospitalised patients in comparison to outpatients.

Conclusion

PCT, CRP and WBC are highest in typical bacterial etiology in CAP but do not allow individual prediction of etiology. In contrast to CRP and WBC, PCT is useful in severity assessment of CAP.     

Small GTP-binding proteins of the Rho- and Ras-subfamilies are not involved in the actin rearrangements induced by attaching and effacing Escherichia coli

Attaching and effacing Escherichia coli (AEEC) are extracellular pathogens that induce the formation of actin-rich structures at their sites of attachment to eukaryotic host cells. We analysed whether small GTP-binding proteins of the Rho- and Ras-subfamilies, which control the cellular actin system, are essential for these bacterial-induced microfilament reorganizations. For this purpose we specifically inactivated them using the Clostridium difficile toxins TcdB-10463 and TcdB-1470. Such treatment led to a dramatic breakdown of the normal actin cytoskeleton, but did not abrogate the bacterial-induced actin rearrangements. Our data therefore indicate that the microfilament reorganizations induced by AEEC are independent of those small GTP-binding proteins that under normal conditions control the dynamics and maintenance of the actin cytoskeleton.     

Soluble Tumor Necrosis Factor Related Apoptosis Inducing Ligand Level as a Predictor of Severity of Sepsis and the Risk of Mortality in Septic Patients

Background

Tumor necrosis factor related apoptosis inducing ligand (TRAIL) as a member of the TNF gene superfamily induces apoptosis primarily in tumor cells. TRAIL also plays an important role in the modulation of inflammatory responses, especially in the process of immune paralysis. The aim of the present study was to examine soluble TRAIL (sTRAIL) levels in septic patients in an attempt to explore the association between sTRAIL level and the risk of mortality.

Methods

Plasma sTRAIL levels were detected by ELISA in 50 septic patients and 20 healthy volunteers. HLA-DR expression in monocytes was detected by flow cytometry. Selective biochemical parameters were recorded, and patients were monitored in a 28-day period for mortality.

Results

The mean plasma sTRAIL level in septic patients was significantly lower than that in healthy controls (16.9±8.3 vs. 68.3±8.6 pg/ml, P<0.01), and was significantly higher in 28-day survivors than those in non-survivors (19.4±9.8 vs. 13.9±4.7 pg/ml, P<0.05). Univariate analysis indicated that plasma sTRAIL level was positively correlated with monocyte and lymphocyte counts and HLA-DR expression level (r = 0.5, P<0.01; r = 0.3, P<0.05; r = 0.43, P<0.01, respectively). STRAIL level was negatively correlated with APACHE II score, BUN and age (r = −0.48, P<0.01; r = −0.29, P<0.05; r = −0.45, P<0.01, respectively). Multiple linear regression analysis indicated that the predictor of plasma soluble TRAIL level was HLA-DR expression (P<0.01).

Conclusion

Low plasma sTRAIL levels were associated with immune paralysis and a high risk of mortality in patients with septic shock. sTRAIL may prove to be a potential biomarker of immune function and predict the survival of septic patients.     

Age and Gender Variations in Cancer Diagnostic Intervals in 15 Cancers: Analysis of Data from the UK Clinical Practice Research Datalink

BackgroundTime from symptomatic presentation to cancer diagnosis (diagnostic interval) is an important, and modifiable, part of the patient’s cancer pathway, and can be affected by various factors such as age, gender and type of presenting symptoms. The aim of this study was to quantify the relationships of diagnostic interval with these variables in 15 cancers diagnosed between 2007 and 2010 using routinely collected data from the Clinical Practice Research Datalink (CPRD) in the UK.MethodsSymptom lists for each cancer were prepared from the literature and by consensus amongst the clinician researchers, which were then categorised into either NICE qualifying (NICE) or not (non-NICE) based on NICE Urgent Referral Guidelines for Suspected Cancer criteria. Multivariable linear regression models were fitted to examine the relationship between diagnostic interval (outcome) and the predictors: age, gender and symptom type.Results18,618 newly diagnosed cancer patients aged ≥40 who had a recorded symptom in the preceding year were included in the analysis. Mean diagnostic interval was greater for older patients in four disease sites (difference in days per 10 year increase in age; 95% CI): bladder (10.3; 5.5 to 15.1; P<0.001), kidney (11.0; 3.4 to 18.6; P=0.004), leukaemia (18.5; 8.8 to 28.1; P<0.001) and lung (10.1; 6.7 to 13.4; P<0.001). There was also evidence of longer diagnostic interval in older patients with colorectal cancer (P<0.001). However, we found that mean diagnostic interval was shorter with increasing age in two cancers: gastric (-5.9; -11.7 to -0.2; P=0.04) and pancreatic (-6.0; -11.2 to -0.7; P=0.03). Diagnostic interval was longer for females in six of the gender non-specific cancers (mean difference in days; 95% CI): bladder (12.2; 0.8 to 23.6; P=0.04), colorectal (10.4; 4.3 to 16.5; P=0.001), gastric (14.3; 1.1 to 27.6; P=0.03), head and neck (31.3; 6.2 to 56.5; P=0.02), lung (8.0; 1.2 to 14.9; P=0.02), and lymphoma (19.2; 3.8 to 34.7; P=0.01). Evidence of longer diagnostic interval was found for patients presenting with non-NICE symptoms in 10 of 15 cancers (mean difference in days; 95% CI): bladder (62.9; 48.7 to 77.2; P<0.001), breast (115.1; 105.9 to 124.3; P<0.001), cervical (60.3; 31.6 to 89.0; P<0.001), colorectal (25.8; 19.6 to 31.9; P<0.001), gastric (24.1; 3.4 to 44.8; P=0.02), kidney (22.1; 4.5 to 39.7; P=0.01), oesophageal (67.0; 42.1 to 92.0; P<0.001), pancreatic (48.6; 28.1 to 69.1; P<0.001), testicular (36.7; 17.0 to 56.4; P< 0.001), and endometrial (73.8; 60.3 to 87.3; P<0.001). Pooled analysis across all cancers demonstrated highly significant evidence of differences overall showing longer diagnostic intervals with increasing age (7.8 days; 6.4 to 9.1; P<0.001); for females (8.9 days; 5.5 to 12.2; P<0.001); and in non-NICE symptoms (27.7 days; 23.9 to 31.5; P<0.001).ConclusionsWe found age and gender-specific inequalities in time to diagnosis for some but not all cancer sites studied. Whilst these need further explanation, these findings can inform the development and evaluation of interventions intended to achieve timely diagnosis and improved cancer outcomes, such as to provide equity across all age and gender groupings.     

Modelling the Impact and Cost-Effectiveness of Biomarker Tests as Compared with Pathogen-Specific Diagnostics in the Management of Undifferentiated Fever in Remote Tropical Settings

Background

Malaria accounts for a small fraction of febrile cases in increasingly large areas of the malaria endemic world. Point-of-care tests to improve the management of non-malarial fevers appropriate for primary care are few, consisting of either diagnostic tests for specific pathogens or testing for biomarkers of host response that indicate whether antibiotics might be required. The impact and cost-effectiveness of these approaches are relatively unexplored and methods to do so are not well-developed.

Methods

We model the ability of dengue and scrub typhus rapid tests to inform antibiotic treatment, as compared with testing for elevated C-Reactive Protein (CRP), a biomarker of host-inflammation. Using data on causes of fever in rural Laos, we estimate the proportion of outpatients that would be correctly classified as requiring an antibiotic and the likely cost-effectiveness of the approaches.

Results

Use of either pathogen-specific test slightly increased the proportion of patients correctly classified as requiring antibiotics. CRP testing was consistently superior to the pathogen-specific tests, despite heterogeneity in causes of fever. All testing strategies are likely to result in higher average costs, but only the scrub typhus and CRP tests are likely to be cost-effective when considering direct health benefits, with median cost per disability adjusted life year averted of approximately $48 USD and $94 USD, respectively.

Conclusions

Testing for viral infections is unlikely to be cost-effective when considering only direct health benefits to patients. Testing for prevalent bacterial pathogens can be cost-effective, having the benefit of informing not only whether treatment is required, but also as to the most appropriate antibiotic; this advantage, however, varies widely in response to heterogeneity in causes of fever. Testing for biomarkers of host inflammation is likely to be consistently cost-effective despite high heterogeneity, and can also offer substantial reductions in over-use of antimicrobials in viral infections.     

C-reactive protein as an early predictor of COVID-19 severity

BackgroundData for predicting severity of patients with COVID-19 infection are sparse and still under investigation. We retrospectively studied whether the admission serum C-reactive protein level (CRP) can serve as nearly predictor of disease severity during COVID-19 infection in comparison with other hematologic and inflammatory markers.MethodsWe included all consecutive patients who were admitted in Cheikh Khalifa International University Hospital, Casablanca, Morocco, between February to April 2020, with a confirmed diagnosis of COVID-19 infection using SARS-CoV-2 viral nucleic acid via RT-PCR. The complete blood count and serum CRP level were routinely measured on admission. All clinical and laboratory data of patients were collected and analyzed. The classification of the disease severity was in accordance with the clinical classification of the WHO interim guidance, and the management of patients were adapted to the national management guideline. We estimated receiver operating characteristic (ROC) curves of blood routine parameters as well as their association with COVID-19 disease severity.Results145 COVID-19 patients were included in the study. The median age (range) was 50 (32-63) years, and 75 (51.7%) were men. 101 patients were classified in the non-severe group and 44 patients in the severe group. Based on disease severity, significant differences were observed in the age, gender, comorbidities, and respiratory symptom. Similarly, the biological analysis found significant differences for the neutrophil count, lymphocyte count, eosinophil count, and CRP level. However, according to ROC curves of these laboratory biomarkers, the AUC of CRP at 0.872 was significantly higher than all other parameters. Further, CRP was independently associated with severity of COVID-19 disease (OR = 1.11, 95% IC (1.01-1.22) and or = 1.13, 95% IC (1.04-1.23)).ConclusionsThis study found that the CRP level at admission represent a simple and independent factor that can be useful for early detection of severity during COVID-19 and the easy guidance of primary care.     

Pre-Treatment Levels of C-Reactive Protein and Squamous Cell Carcinoma Antigen for Predicting the Aggressiveness of Pharyngolaryngeal Carcinoma

The levels of squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) can be used to predict tumor invasion, lymph node metastasis, staging and survival in patients with oral cavity cancer. The present study analyzed the relationship between pre-treatment levels of SCC-Ag and CRP in relation to clinicopathological factors in patients with pharyngolaryngeal cancer (PLC) and determined whether elevated levels of CRP and SCC-Ag were associated with tumor metabolic activity via [18F] fluorodeoxyglucose positron emission tomography (FDG-PET). We retrospectively recruited one hundred and six PLC patients between June 2008 and December 2011. All patients received computed tomography (CT)/magnetic resonance imaging (MRI) and FDG-PET staging analyses, and the serum levels of SCC-Ag and CRP in these patients were measured prior to treatment. A SCC-Ag level ≥2.0 ng/ml and a CRP level ≥5.0 mg/L were significantly associated with clinical stage (P<0.001), clinical tumor status (P<0.001), and clinical nodal status (P<0.001). The elevation of both SCC-Ag and CRP levels was correlated with the standardized uptake value (SUV) max of the tumor (≥8.6 mg/L) and lymph nodes (≥5.7 ng/ml) (P = 0.019). The present study demonstrated that the presence of high levels of both pre-treatment SCC-Ag and CRP acts as a predictor of clinical stage, clinical tumor status, and clinical nodal status in patients with PLC. Moreover, elevated levels of SCC-Ag and CRP were associated with a high metabolic rate as well as the proliferative activity measured according to the SUVmax of the tumor and lymph nodes. Therefore, elevated levels of these two factors have the potential to serve as biomarkers for the prediction of tumor aggressiveness in cases of PLC.     

Diagnostic Value of Symptom Screening for Pulmonary Tuberculosis in China

ObjectiveTo evaluate the diagnostic value of symptom screening for tuberculosis (TB) case finding defined in National Tuberculosis Control Program in China (China NTP) among elderly people(≥65 years) and younger people(<65 years).MethodsWe made a secondary analysis in a population-based TB prevalence survey in China in 2010. Questionnaire including information for cough and haemoptysis was completed by face to face interview, and then chest radiography was conducted in all eligible participants. Sputum smear and culture were followed for all TB suspects. We calculated the odds ratios (OR), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the area under the receiver operating characteristic curve (AUC) of using different symptoms for screening to detect bacteriologically positive TB in subpopulations stratified by age 65, to evaluate the performance of symptom screening for TB.FindingsOf 315 newly diagnosed bacteriologically positive TB, 131 patients (41.59%) were elderly, and 48.57% of TB patients were asymptomatic. Nearly 50% patients did not present cough of any duration, and less than half present cough more than 2 weeks, a defined suspected symptom in China NTP. Cough of any duration was reported more in patients aged under 65 than those in elderly, especially for the acute cough (9.78% vs 6.87%). Those symptoms defined by China NTP were reported by less than half participants in two subpopulations. Acute cough (<2 weeks) was an independent predictor of TB in people aged under 65 (adjusted OR: 3.3, 95% CI: 2.0-5.5), but not in those aged 65 and above (adjusted OR: 1.4, 95% CI: 0.7-2.9). The specificity for each symptom was significantly higher in participants aged under 65 (P<0.01), and sensitivities of most symptoms were significantly higher among elderly (P<0.05 or P<0.01). When compared with cough for 2 weeks and more, using cough of any duration for symptom screening increased the sensitivity from 42.9% to 51. % for all participants, and the AUC increased from 0.70 to 0.74 for participants aged under 65 without significant difference.ConclusionsThere is a high percent of asymptomatic TB patients, and those symptoms adopted in China NTP for screening is poorly predictive for TB. The presence of TB symptoms, the sensitivities and specificities of symptoms for TB were distinct between two subpopulations cut by age 65, implying different case finding strategies should be established for them. The current case finding strategy should be improved, and further studies should be done to evaluate the performance and cost-effectiveness of different symptom screening strategy.     

Circulating TRAIL shows a significant post-partum decline associated to stressful conditions

Background

Since circulating levels of TNF-related apoptosis inducing ligand (TRAIL) may be important in the physiopathology of pregnancy, we tested the hypothesis that TRAIL levels change at delivery in response to stressful conditions.

Methods/Principal Findings

We conducted a longitudinal study in a cohort of 73 women examined at week 12, week 16, delivery and in the corresponding cord blood (CB). Serum TRAIL was assessed in relationship with maternal characteristics and to biochemical parameters. TRAIL did not vary between 12 (67.6±27.6 pg/ml, means±SD) and 16 (64.0±16.2 pg/ml) weeks'' gestation, while displaying a significant decline after partum (49.3±26.4 pg/ml). Using a cut-off decline >20 pg/ml between week 12 and delivery, the subset of women with the higher decline of circulating TRAIL (41.7%) showed the following characteristics: i) nullipara, ii) higher age, iii) operational vaginal delivery or urgent CS, iv) did not receive analgesia during labor, v) induced labor. CB TRAIL was significantly higher (131.6±52 pg/ml) with respect to the corresponding maternal TRAIL, and the variables significantly associated with the first quartile of CB TRAIL (<90 pg/ml) were higher pre-pregnancy BMI, induction of labor and fetal distress. With respect to the biochemical parameters, maternal TRAIL at delivery showed an inverse correlation with C-reactive protein (CRP), total cortisol, glycemia and insulin at bivariate analysis, but only with CRP at multivariate analysis.

Conclusions

Stressful partum conditions and elevated CRP levels are associated with a decrease of circulating TRAIL.     

A Unique Role for the Host ESCRT Proteins in Replication of Tomato bushy stunt virus

Plus-stranded RNA viruses replicate in infected cells by assembling viral replicase complexes consisting of viral- and host-coded proteins. Previous genome-wide screens with Tomato bushy stunt tombusvirus (TBSV) in a yeast model host revealed the involvement of seven ESCRT (endosomal sorting complexes required for transport) proteins in viral replication. In this paper, we show that the expression of dominant negative Vps23p, Vps24p, Snf7p, and Vps4p ESCRT factors inhibited virus replication in the plant host, suggesting that tombusviruses co-opt selected ESCRT proteins for the assembly of the viral replicase complex. We also show that TBSV p33 replication protein interacts with Vps23p ESCRT-I and Bro1p accessory ESCRT factors. The interaction with p33 leads to the recruitment of Vps23p to the peroxisomes, the sites of TBSV replication. The viral replicase showed reduced activity and the minus-stranded viral RNA in the replicase became more accessible to ribonuclease when derived from vps23Δ or vps24Δ yeast, suggesting that the protection of the viral RNA is compromised within the replicase complex assembled in the absence of ESCRT proteins. The recruitment of ESCRT proteins is needed for the precise assembly of the replicase complex, which might help the virus evade recognition by the host defense surveillance system and/or prevent viral RNA destruction by the gene silencing machinery.     

The Lipid-Bound Apolipoprotein A-I Cysteine Mutant (N74C) Inhibits the Activation of NF-κB,JNK and p38 in Endotoxemic Mice and RAW264.7 Cells

Our previous studies showed that recombinant high-density lipoprotein (rHDL) rHDL74 exhibited higher anti-inflammatory capabilities compared to wild-type rHDL (rHDLwt), while rHDL228 showed hyper-proinflammation. In this paper, we further investigated the potential mechanisms involved in their different inflammatory functions using two models: endotoxemic mice and the RAW264.7 inflammation model. Our results showed that 24 h after the injection of lipopolysaccharide (LPS), mice treated with rHDL74 had a significant decrease in plasma CRP (P<0.01 vs. rHDLwt; P<0.01 vs. LPS), MCP-1 (P<0.05 vs. rHDLwt; P<0.01 vs. LPS) and CD14 (P<0.01 vs. LPS) compared with the mice treated with rHDLwt or the controls that received LPS only. Similar to our previous study, rHDL228 increased the plasma level of CRP (P<0.05 vs. LPS) and MCP-1 (P<0.01 vs. LPS). Our immunohistochemistry and western blot analysis showed that rHDL74 inhibited the activation of NF-κB in endotoxemic mice and JNK and p38 in the RAW264.7 inflammation model, while rHDL228 exacerbated the activation of NF-κB and ERK. In summary, our data suggest that rHDL74 exhibits higher anti-inflammatory activity by decreasing inflammatory factors and inhibiting the activation of NF-κB, JNK and p38, while rHDL228 appears to be hyper-proinflammation by increasing these inflammatory factors and aggravating the activation of NF-κB and ERK.     

Streptococcal Disease Control in an Ambulatory Practice—Explicit Criteria for Throat Cultures

A throat culture protocol was implemented in an ambulatory practice to standardize culturing and to conserve laboratory resources. A retrospective chart audit during three one-month study periods preceding (1976) and following protocol implementation (1978 and 1979) showed a significant effect on care-provider compliance with culture criteria (P<.0001). During a three-year period there was a significant decrease in the number of cultures done for patients younger than 2 years of age (23.6%, 6.9% and 0%; P<.001) and asymptomatic patients (19.4%, 13.9% and 3.1%; P<.001). From 1976 to 1978 there was a 50% decrease in cultures per 100 visits (12.3 versus 6.0). This change resulted in a three-year cost savings of $79,944. Of interest was the significant increase in the percentage of positive cultures between 1977 and 1978 (12.0% versus 18.8%; P<.001). This latter finding suggests that culture protocol criteria were selective for patients with pathogens.     

Correlation of Prostatic Urethral Angle with the Severity of Urinary Symptom and Peak Flow Rate in Men with Small Prostate Volume

Purpose

To evaluate the effects of prostatic anatomical factors on male lower urinary tract symptoms (LUTS) and the peak flow rate (Qmax) in patients with small prostate volume (PV).

Materials and Methods

Records were obtained from a prospectively maintained database of first-visit men with LUTS. Patients whose total PV (TPV) was greater than 30 mL were excluded; 444 patients were enrolled in the study. The TPV, transitional zone volume (TZV), transitional zone index (TZI), intravesical prostatic protrusion (IPP), and prostatic urethral angle (PUA) were measured by transrectal ultrasonography. LUTS were evaluated using the International Prostate Symptom Score (IPSS) and the Overactive Bladder Symptom Score (OABSS) questionnaires. Uroflowmetric measurements were also made.

Results

PUA (r = 0.269, P<0.001), TZV (r = 0.160, P<0.001), and TZI (r = 0.109, P = 0.022) significantly correlated with the IPSS. Qmax (r = −0.334, P<0.001) and OABSS (r = 0.211, P<0.001) correlated only with PUA. In a multivariate regression analysis, PUA and age were independently associated with IPSS, OABSS, and Qmax. For IPSS of 20 or greater, the area under the ROC curve (AUC) of PUA was 0.667 and the cut-off value was 43.7°. When Qmax was 10 mL/s or less, the AUC of PUA was 0.664 and the cut-off value was 43.5°.

Conclusions

PUA has a significant association with symptom severity and Qmax among prostatic anatomical factors analyzed in men with LUTS and small PV. PUA should be considered as an important clinical factor in male LUTS management. Furthermore, the impact of PUA on response to medical treatment and disease progression needs to be investigated.     

Hepatitis C virus infection sensitizes human hepatocytes to TRAIL-induced apoptosis in a caspase 9-dependent manner

Apoptosis of infected cells represents a key host defense mechanism against viral infections. The impact of apoptosis on the elimination of hepatitis C virus (HCV)-infected cells is poorly understood. The TRAIL has been implicated in the death of liver cells in hepatitis-infected but not in normal liver cells. To determine the impact of TRAIL on apoptosis of virus-infected host cells, we studied TRAIL-induced apoptosis in a tissue culture model system for HCV infection. We demonstrated that HCV infection sensitizes primary human hepatocytes and Huh7.5 hepatoma cells to TRAIL induced apoptosis in a dose- and time-dependent manner. Mapping studies identified the HCV nonstructural proteins as key mediators of sensitization to TRAIL. Using a panel of inhibitors targeting different apoptosis pathways, we demonstrate that sensitization to TRAIL is caspase-9 dependent and mediated in part via the mitochondrial pathway. Sensitization of hepatocytes to TRAIL-induced apoptosis by HCV infection represents a novel antiviral host defense mechanism that may have important implications for the pathogenesis of HCV infection and may contribute to the elimination of virus-infected hepatocytes.     

Reprint of: Virus-binding proteins and their roles in shrimp innate immunity

Disease outbreaks caused by viral pathogens constitute a major limitation to development of the shrimp aquaculture industry. Many research have been conducted to better understand how host shrimp respond to viral infections with the aim of using the gained knowledge to develop better strategies for disease management and control. One approach has been to study the interactions between host and viral proteins, and particularly host virus-binding proteins that might play an important role in the viral infection process. Within the past five years, increasing numbers of virus-binding proteins (VBPs) have been reported in shrimp. Characterization of these molecules has emphasized on their potential therapeutic applications by demonstrating their activities in inhibition of viral replication via in vivo neutralization assay. However, signaling to induce innate antiviral immune responses as a consequence of binding between viral proteins and VBPs remain to be fully elucidated.     

Downregulation of CD94/NKG2A inhibitory receptors on CD8+ T cells in HIV infection is more pronounced in subjects with detected viral load than in their aviraemic counterparts

MicroRNAs play critical role in regulating gene expression. MicroRNA profile of particular cell type bears the signature of cell type specific gene expression. Given that viral pathogens replicate by evading host defenses, research is now focused on the miRNA-regulated genes that critically regulate HIV-1 propagation in human host cells.