Search

Background/Aim: Elevation in liver enzymes and hepatic fat may indicate a higher susceptibility to cardiovascular disease (CVD). This research sought to find anthropometric/biochemical variables significantly related to the alanine aminotransferase (ALT) increase in healthy populations. Methods: Nine hundred healthy subjects were included in a 3-year prospective cohort study. The initial screening revealed that 538 were found to be nondiabetic (fasting glucose < 126 mg/dL) and had normal ALT levels. Among them, 79 individuals with slightly elevated ALT levels after three years were assigned to the elevated ALT group. Of the remaining 459 participants, 241 subjects matched to the increased ALT group were the control group. Results: After three years of follow-up, individuals with elevated ALT showed notably higher aspartate aminotransferase (AST), ALT, gamma-glutamyl-transferase (g-GT), high sensitivity C-reactive protein (hs-CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2 ) activity, oxidised low-density lipoprotein (ox-LDL), urinary 8-epi-prostaglandin F2a (8-epi-PGF2a) levels and brachial-ankle pulse wave velocity (ba-PWV) in comparison to the control group. Changes (D) in ALT showed a positive correlation with D AST, D gammaGT, D hs-CRP, D Lp-PLA2 activity, D ox-LDL, D urinary 8-epi-PGF2a and D ba-PWV. Furthermore, a direct positive link was observed between the D Lp-PLA2 activity and D AST, D ox-LDL and D ba-PWV. Conclusion: Increased Lp-PLA2 activity and other CVD risk indicators were observed to have a pronounced association with elevated ALT levels. This mild ALT elevation could potentially contribute to chronic low-grade inflammation.

High-sensitivity C-reactive protein (hs-CRP) is a marker of systemic inflammation and is associated with developing dyslipidemia. However, the causality between hs-CRP and dyslipidemia remains unresolved. This study aimed to investigate the relationship between hs-CRP concentrations and dyslipidemia and to explore the potential causal link using Mendelian randomization (MR) analysis. A nested case–control study was conducted with 1174 participants, and genotype data were analyzed using the Korean Chip. A genome-wide association study (GWAS) identified rs76400217 as a suitable instrumental variable (IV) due to its significant association with hs-CRP (p < 10−8). Logistic regression models, adjusted for confounders, were used to evaluate the association between hs-CRP and dyslipidemia. An MR analysis was performed using a two-stage least squares (2SLS) method, with rs76400217 as the IV to assess causality. Logistic regression showed a significant association between hs-CRP concentrations and dyslipidemia (OR 2.08, 95% CI: 1.81–2.39, p < 0.001). This association remained significant after adjusting for factors such as age, sex, alcohol consumption, and BMI. The MR analysis using rs76400217 as the IV confirmed the strong associations with hs-CRP concentrations (p < 0.001) in all models, but the causality between hs-CRP and dyslipidemia was not statistically significant. Thus, no evidence of a causal relationship between hs-CRP and the risk of dyslipidemia was found in the Korean population. The strong association observed between hs-CRP and dyslipidemia may be due to other contributing factors rather than a direct cause. [ABSTRACT FROM AUTHOR]

Food packaging films play a vital role in preserving and protecting food. The focus has gradually shifted to safety and sustainability in the preparation of functional food packaging materials. In this study, a bisquaternary ammonium salt of tannic acid (BQTA) was synthesized, and the bioplastics based on BQTA and polyvinyl alcohol (PVA) were created for packaging applications. The impact of BQTA on antibacterial effect, antioxidant capacity, opacity, ultraviolet (UV) protective activity, mechanical strength, thermal stability, and anti-fog of the resultant bioplastics was examined. In vitro antibacterial experiments confirmed that BQTA possesses excellent antimicrobial properties, and only a trace amount addition of BQTA in PVA composite film could inhibit about 100% of Escherichia coli and Staphylococcus aureus. Compared to BQTA/PVA bioplastics with pure PVA, the experiment findings demonstrate that BQTA/PVA bioplastics show strong antioxidant and UV protection action and the performance of fruit preservation. It also revealed a small improvement in thermal stability and tensile strength. The small water contact angle, even at low BQTA concentrations, gave BQTA/PVA bioplastics good anti-fog performance. Based on the findings, bioplastics of BQTA/PVA have the potential to be used to create packaging, and they can be applied as the second (inner) layer of the primary packaging to protect food freshness and nutrition due to their antioxidant activity and biocompatibility. [ABSTRACT FROM AUTHOR]

Development of the erythrocytic malaria parasite requires targeting of parasite proteins into multiple compartments located within and beyond the parasite confine. Beyond the PEXEL/ VTS pathway and its characterized players, increasing amount of evidence has highlighted the existence of proteins exported using alternative export-signal(s)/pathway(s); hence, the exportomes currently predicted are incomplete. The nature of these exported proteins which could have a prominent role in most of the P lasmodium species remains elusive. Using P . yoelii variant proteins, we identified a signal associated to lipophilic region that mediates export of P . yoelii proteins. This non- PEXEL signal termed PLASMED is defined by semi-conserved residues and possibly a secondary structure. In vivo characterization of exported-proteins indicated that PLASMED is a bona fide export-signal that allowed us to identify an unseen P . yoelii exportome. The repertoire of the newly predicted exported proteins opens up perspectives for unravelling the remodelling of the host-cell by the parasite, against which new therapies could be elaborated. [ABSTRACT FROM AUTHOR]

Drug resistance in P lasmodium falciparum remains a challenge for the malaria eradication programmes around the world. With the emergence of artemisinin resistance, the efficacy of the partner drugs in the artemisinin combination therapies ( ACT) that include quinoline-based drugs is becoming critical. So far only few resistance markers have been identified from which only two transmembrane transporters namely PfMDR1 (an ATP-binding cassette transporter) and PfCRT (a drug-metabolite transporter) have been experimentally verified. Another P . falciparum transporter, the ATP-binding cassette containing multidrug resistance-associated protein ( PfMRP2) represents an additional possible factor of drug resistance in P . falciparum. In this study, we identified a parasite clone that is derived from the 3D7 P . falciparum strain and shows increased resistance to chloroquine, mefloquine and quinine through the trophozoite and schizont stages. We demonstrate that the resistance phenotype is caused by a 4.1 kb deletion in the 5′ upstream region of the pfmrp2 gene that leads to an alteration in the pfmrp2 transcription and thus increased level of PfMRP2 protein. These results also suggest the importance of putative promoter elements in regulation of gene expression during the P . falciparum intra-erythrocytic developmental cycle and the potential of genetic polymorphisms within these regions to underlie drug resistance. [ABSTRACT FROM AUTHOR]

: A key step for the survival of the malaria parasite is the release from and subsequent invasion of erythrocytes by the merozoite. Differences in the efficiency of these two linked processes have a direct impact on overall parasite burden in the host and thereby virulence. A number of parasite proteases have recently been shown to play important roles during both merozoite egress as well as merozoite invasion. The rodent malaria parasite Plasmodium yoelii has been extensively used to investigate the mechanisms of parasite virulence in vivo and a number of important proteins have been identified as being key contributors to pathology. Here we have utilized transcriptional comparisons to identify two protease-like SERAs as playing a potential role in virulence. We show that both SERAs are non-essential for blood stage development of the parasite though they provide a subtle but important growth advantage in vivo. In particular SERA2 appears to be an important factor in enabling the parasite to fully utilize the whole age repertoire of circulating erythrocytes. This work for the first time demonstrates the subtle contributions different protease-like SERAs make to provide the parasite with a maximal capacity to successfully maintain an infection in the host. [ABSTRACT FROM AUTHOR]

Malaria remains a serious public health problem with significant morbidity and mortality accounting for nearly 20% of all childhood deaths in Africa. The cyclical invasion, cytoadherence and destruction of the host's erythrocyte by the parasite are responsible for the observed disease pathology. The invasive form of the parasite, the merozoite, uses a complex set of interactions between parasite ligands and erythrocyte receptors that leads to the formation of a tight junction and ultimately successful erythrocyte invasion. Understanding the molecular mechanism underlying host cell recognition and invasion is crucial for the development of a targeted intervention strategy. Two parasite protein families termed reticulocyte-binding-like protein homologues ( RBL) and the erythrocyte-binding-like ( EBL) protein family are conserved in all Plasmodium species and have been shown to play an important role in host cell recognition and invasion. Over the last few years significant new insights have been gained in understanding the function of the RBL family and this review attempts to provide an update with a specific focus on the role of RBL in signal transduction pathways during invasion. [ABSTRACT FROM AUTHOR]

To evaluate the alarm notification of artificial intelligence in detecting parasites on the KU-F40 Fully Automatic Feces Analyzer and provide a reference for clinical diagnosis in parasite diseases. A total of 1030 fecal specimens from patients in our hospital from May to June 2023 were collected, and parasite detection studies were conducted using the KU-F40 automated feces analyzer (normal mode method, floating-sedimentation mode method), acid-ether sedimentation method, and direct smear microscopy method, respectively. The positive detection rate of parasites in the 1030 fecal specimens was 22.9% (236 cases), of which the KU-F40 normal mode method had a detection rate of 16.3% (168 cases), the acid-ether sedimentation method had a detection rate of 19.0% (196 cases), and the direct smear microscopy method had a detection rate of 13.1% (135 cases). The detection rates of the first 2 methods were higher than those of the direct smear microscopy method, and the difference was statistically significant (P < .05). The detection rate of the KU-F40 floating-sedimentation mode method was 11.9% (123 cases), which was lower than that of the direct smear microscopy, and the difference was not statistically significant (P > .05). The sensitivity of the KU-F40 normal mode method, acid-ether sedimentation method, direct smear microscopy method, and the KU-F40 floating-sedimentation mode method were 71.2%, 83.1%, 57.2%, and 52.1%, respectively, and the specificity was 94.7%, 100%, 100%, and 97.7%, respectively. The coincidence rates of the KU-F40 normal mode method was 90.78%, with Kappa values of 0.633. The positive detection rate of parasites using the KU-F40 normal mode method is higher than that using the direct smear microscopy method. It has high sensitivity and specificity and has advantages such as high automation and fast detection speed. It can replace the microscopy method for routine screening and has higher clinical application value in the diagnosis of intestinal parasitic diseases., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This study aims to report the clinical characteristics of a child with autosomal recessive polycystic kidney disease (ARPKD) within a Chinese Zhuang ethnic family., Methods: We used whole exome sequencing (WES) in the family to examine the genetic cause of the disease. Candidate pathogenic variants were validated by Sanger sequencing., Results: We identified previously unreported mutations in the PKHD1 gene of the proband with ARPKD through WES: a splice site mutation c.6809-2A > T, a nonsense mutation c.4192C > T(p.Gln1398Ter), and a missense mutation c.2181T > G(p.Asn727Lys). Her mother is a heterozygous carrier of c.2181T > G(p.Asn727Lys) mutation. Her father is a carrier of c.6809-2A > T mutation and c.4192C > T(p.Gln1398Ter) mutation., Conclusions: The identification of novel mutations in the PKHD1 gene through WES not only expands the spectrum of known variants but also potentially enhances genetic counseling and prenatal diagnostic approaches for families affected by ARPKD., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Infections by malaria parasites can lead to very different clinical outcomes, ranging from mild symptoms to death. Differences in the ability of the spleen to deal with the infected red blood cells (iRBCs) are linked to differences in virulence. Using virulent and avirulent strains of the rodent malaria parasite Plasmodium yoelii, we investigated how parasite virulence modulates overall spleen function. Following parasite invasion, a difference in parasite virulence was observed in association with different levels of spleen morphology and iRBC rigidity, both of which contributed to enhanced parasite clearance. Moreover, iRBC rigidity as modulated by the spleen was demonstrated to correlate with disease outcome and thus can be used as a robust indicator of virulence. The data indicate that alterations in the biomechanical properties of iRBCs are the result of the complex interaction between host and parasite. Furthermore, we confirmed that early spleen responses are a key factor in directing the clinical outcome of an infection. IMPORTANCE The spleen and its response to parasite infection are important in eliminating parasites in malaria. By comparing P. yoelii parasite lines with different disease outcomes in mice that had either intact spleens or had had their spleens removed, we showed that upon parasite infection, the spleen exhibits dramatic changes that can affect parasite clearance. The spleen itself directly impacts RBC deformability independently of parasite genetics. The data indicated that the changes in the biomechanical properties of malaria parasite-infected RBCs are the result of the complex interaction between host and parasite, and RBC deformability itself can serve as a novel predictor of clinical outcome. The results also suggest that early responses in the spleen are a key factor directing the clinical outcome of an infection.