Derangements in bilirubin metabolism and/or dysfunctions in the hepato-biliary system lead to the unhealthy buildup of bilirubin in blood, resulting in jaundice. During the course of this disorder, circulating red cells are invariably subjected to toxic effects of serum bilirubin and an array of inflammatory compounds. This study aimed to investigate the vibrational spectroscopy of live red cells in jaundice using micro-Raman spectroscopy combined with optical-trap. Red cells from blood samples of healthy volunteers and patients with jaundice were optically immobilized and micro-Raman probed using a 785 nm diode laser. Raman signatures from red cells in jaundice exhibited significant variations from the normal and the spectral-markers were obtained from multivariate analytical methods. This research gives insightful views on how different pathologies can act as "stress-milieus" for red cells in circulation, possibly impeding their normal functions and also exasperating anemia. Raman spectroscopy, an emerging bio-analytical technique, is sensitive in detecting molecular-conformations in situ, at cellular-levels and in real-time. This study could pave way in understanding fundamental red cell behavior in different diseases by analyzing Raman markers.
One of the beneficial effects of non-digestible oligosaccharides (NDOs) is their anti-inflammatory effects on host animals. While conventional animal studies require that analysis be done after samples have been taken from the host, zebrafish larvae are optically transparent upon hatching and this provides an opportunity for observations to be made within the living zebrafish larvae. This study aimed to take advantage of the optical transparency of zebrafish larvae to study the nitric oxide (NO) reducing effects of NDOs through the use of lipopolysaccharide (LPS) from Salmonella enterica serovar (ser.) Enteritidis (S. Enteritidis) to induce cardiac NO production. Prior to running the above experiment, an acute toxicity assay was conducted in order to determine the appropriate concentration of oligosaccharides to be used. The oligosaccharides tested consisted of oligosaccharides which were extracted from palm kernel cake with a degree of polymerization (DP) equal to or less than six (OligoPKC), commercial mannanoligosaccharide (MOS) and commercial fructooligosaccharide (FOS). Acute toxicity test results revealed that the OligoPKC has a LC50 of 488.1 μg/ml while both MOS and FOS were non-toxic up to 1,000 μg/ml. Results of the in vivo NO measurements revealed that all three NDOs were capable of significantly reducing NO levels in LPS stimulated zebrafish embryos. In summary, at 250 μg/ml, OligoPKC was comparable to MOS and better than FOS at lowering NO in LPS induced zebrafish larvae. However, at higher doses, OligoPKC appears toxic to zebrafish larvae. This implies that the therapeutic potential of OligoPKC is limited by its toxicity.
Background/Purpose: In this systematic review and meta-analysis, we assessed the effects of exercise (EX) combined with calorie restriction (CR) intervention on inflammatory biomarkers, and correlations between biomarkers and participants' characteristics were calculated in overweight and obese adults. Methods: An article search was conducted through PubMed, Web of Science, EMBASE, the Cochrane database, Scopus, and Google Scholar to identify articles published up to April 2021. Studies that examined the effect of EX + CR intervention on inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and compared them with a CR trial in overweight and obese adults were included. We calculated the pooled effect by meta-analysis, identified the correlations (between inflammatory biomarkers and participants' characteristics) through meta-regression, and explored the beneficial variable through subgroup analysis. The Cochrane risk of bias tool and Methodological Index for Non-randomized Studies were used to assess the risk of bias for the included trials. Results: A total of 23 trials, including 1196 overweight and obese adults, were included in the meta-analysis. The pooled effect showed that EX + CR intervention significantly decreased CRP levels (P = 0.02), but had no effect on IL-6 (P = 0.62) and TNF-α (P = 0.11). Meta-regression analysis showed that the effect of EX + CR on CRP, IL-6, and TNF-α changes was correlated with lifestyle behavior of adults (Coef. = -0.380, P = 0.018; Coef. = -0.359, P = 0.031; Coef. = -0.424, P = 0.041, respectively), but not with age and BMI. The subgroup analysis results revealed that participants with sedentary lifestyle behavior did not respond to EX + CR intervention, as we found no changes in CRP, IL-6, and TNF-α concentrations (P = 0.84, P = 0.16, P = 0.92, respectively). However, EX + CR intervention significantly decreased CRP (P = 0.0003; SMD = -0.39; 95%CI: -0.60 to -0.18), IL-6 (P = 0.04; SMD = -0.21; 95%CI: -0.40 to -0.01) and TNF-α (P = 0.006; SMD = -0.40, 95%CI: -0.68 to -0.12) in adults without a sedentary lifestyle or with a normal lifestyle. Furthermore, the values between sedentary and normal lifestyle subgroups were statistically significant for CRP, IL-6, and TNF-α. Conclusion: Our findings showed that combination EX + CR intervention effectively decreased CRP, IL-6, and TNF-α in overweight and obese adults with active lifestyles, but not with sedentary lifestyle behavior. We suggest that 'lifestyle behavior' is a considerable factor when designing new intervention programs for overweight or obese adults to improve their inflammatory response.
Background: Coronavirus disease (COVID-19) manifests many clinical symptoms, including an exacerbated immune response and cytokine storm. Autoantibodies in COVID-19 may have severe prodromal effects that are poorly understood. The interaction between these autoantibodies and self-antigens can result in systemic inflammation and organ dysfunction. However, the role of autoantibodies in COVID-19 complications has yet to be fully understood. Methods: The current investigation screened two independent cohorts of 97 COVID-19 patients [discovery (Disc) cohort from Qatar (case = 49 vs. control = 48) and replication (Rep) cohort from New York (case = 48 vs. control = 28)] utilizing high-throughput KoRectly Expressed (KREX) Immunome protein-array technology. Total IgG autoantibody responses were evaluated against 1,318 correctly folded and full-length human proteins. Samples were randomly applied on the precoated microarray slides for 2 h. Cy3-labeled secondary antibodies were used to detect IgG autoantibody response. Slides were scanned at a fixed gain setting using the Agilent fluorescence microarray scanner, generating a 16-bit TIFF file. Group comparisons were performed using a linear model and Fisher's exact test. Differentially expressed proteins were used for KEGG and WIKIpathway annotation to determine pathways in which the proteins of interest were significantly over-represented. Results and conclusion: Autoantibody responses to 57 proteins were significantly altered in the COVID-19 Disc cohort compared to healthy controls (p ≤ 0.05). The Rep cohort had altered autoantibody responses against 26 proteins compared to non-COVID-19 ICU patients who served as controls. Both cohorts showed substantial similarities (r 2 = 0.73) and exhibited higher autoantibody responses to numerous transcription factors, immunomodulatory proteins, and human disease markers. Analysis of the combined cohorts revealed elevated autoantibody responses against SPANXN4, STK25, ATF4, PRKD2, and CHMP3 proteins in COVID-19 patients. The sequences for SPANXN4 and STK25 were cross-validated using sequence alignment tools. ELISA and Western blot further verified the autoantigen-autoantibody response of SPANXN4. SPANXN4 is essential for spermiogenesis and male fertility, which may predict a potential role for this protein in COVID-19-associated male reproductive tract complications, and warrants further research.