Journal of Biosciences最新文献

Biliary atresia (BA) is a prominent cause of liver cirrhosis in pediatric patients with a high pediatric end-stage liver disease (PELD) score and a Laennec score of 4 at the Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia. Bile duct-ligated rat models have been used to mimic the clinical condition of BA partially. This study aims to evaluate the potential miRNAs of preconditioned umbilical-cord mesenchymal stem-cell exosomes (UC-MSC-exosomes) in comparison with the combined exosomes-HGF effect on liver histology, liver function, and hepatocyte-signaling in bile duct-ligated rats. Characterization of preconditioned UC-MSC-exosomes fulfilled the ISEV 2018 criteria. Liver histology showed trends of hepatocytes, inflammatory cells, and oval cell numbers returning to slightly below normal levels post-preconditioned UC-MSC-exosomes or the exosomes-HGF combination, with no statistically significant difference. A significant difference in bile duct proliferation post-preconditioned UC-MSC-exosomes or the exosomes-HGF combination was observed when compared with the control. Trends towards lower deposition of collagen around the porta area and total area fractions post-preconditioned UC-MSC-exosomes or the exosomes-HGF combination showed no statistically significant difference; however, there was a slightly lower total collagen area fraction in the exosomes-HGF combination group. Functional hepatocyte preservation was indicated by increased albumin expression and partially improved CYP3A4 levels post-preconditioned UC-MSC-exosomes or the exosomes-HGF combination. There was also a different trend in functional hepatocyte biochemical markers, SGOT (AST) and SGPT (ALT), between preconditioned UC-MSC-exosomes and the exosomes-HGF combination. NanoString microarray analysis of liver tissue and bioinformatics analysis were done to investigate in-depth hepatocyte signaling. miRNA profiling of the liver from preconditioned UC-MSC-exosomes identified the upregulation of hsa-miR-1-3p and hsa-miR-372-3p, which inhibit key signaling pathways, e.g., MAPK, PI3K-AKT, and NF-κB, and the downregulation of hsa-miR-520a-3p, which promotes hepatocyte proliferation and survival. miRNA profiles of the liver from the exosomes-HGF combination identified five different miRNA expressions (upregulated hsa-miR-144-3p, hsa-let7-5p, hsa-let7a-5p, hsa-let7e-5p, and hsa-miR-32-5p) and shared only one similar miR with the exosomes-treated liver (downregulated hsa-520a-3p). These miR differences contribute to the hepatocyte signaling in the exosomes-HGF combination group. Preconditioned UC-MSC-exosomes preserve functional hepatocytes in bile duct-ligated rats through alternate miR-mediated signaling rather than HGF signaling.

Synaptic plasticity within cortico-striatal circuits critically influences learning and behavior, with the nucleus accumbens (NAc) serving as a key mediating structure. Within the NAc, medium spiny neurons (MSNs) are known to mediate input integration, whose dendritic calcium levels are thought to influence cortico-striatal plasticity. Calcium responses have been observed to correlate with firing frequency and earlier firing onset. Inward rectifying potassium (K_IR) currents inactivate significantly in ~40% of NAc MSNs. Studies have shown that this inactivation enhances firing frequency and advances firing onset. On the basis of these findings, we hypothesized that K_IR inactivation may enhance intracellular calcium levels in MSNs, with implications for synaptic plasticity. Using an 189-compartment computational model of the MSN, the influence of K_IR inactivation on calcium dynamics was investigated. We found that the amplitude of calcium influx was more than twice as large in the tertiary dendrite and at least 9% higher for higher input currents in response to K_IR inactivation. Additionally, the average calcium concentration increased by up to 26.1% in the soma, with enhancements of 4.3-21.4% in the dendrites. Our findings suggest that K_IR inactivation may significantly modulate synaptic plasticity, thereby impacting the learning mediated by the NAc core.

T-cells are important arms of our immune system and are central to our fight against pathogens and cancers (Baral et al. 2019a; Waldman et al. 2020). They recognize infected and cancerous cells and help destroy them while leaving uninfected/normal cells intact. They accomplish this tricky task with exquisite precision. How they do so has been an enigma and the subject of intense investigation for decades (Chakraborty and Weiss 2014; Courtney et al. 2018).

Consider the classic Ebbinghaus illusion in figure 1: the orange circle on the right seems bigger, even though both orange circles have the same size. Such size illusions occur in the real world too: in fact, a common dieting trick is to serve the same food on a smaller plate, which makes it appear larger, so you end up eating less. Why do we get fooled by such size illusions?

A classic result in theoretical ecology states that an increase in the proportion of cooperative interactions in unstructured ecological communities leads to a loss of stability to external perturbations. However, the fate and composition of the species that constitute an unstable ecological community following such perturbations remains relatively unexplored. Here, we used an individual-based model to study the population dynamics of unstructured communities following external perturbations to species abundances. We found that while increasing the number of cooperative interactions does indeed increase the probability that a community will experience an extinction following a perturbation, the entire community is rarely wiped out following a perturbation. Instead, only a subset of the ecological community is driven to extinction, and the species that become extinct are more likely to be those engaged in a greater number of competitive interactions. Thus, the resultant community formed after a perturbation has a higher proportion of cooperative interactions than the original community. We showed that this result could be explained by studying the dynamics of the species engaged in the highest number of competitive interactions: After an external perturbation, those species that compete with such a 'top competitor' are more likely to become extinct than expected by chance alone, whereas those that are engaged in cooperative interactions with such a species are less likely to become extinct than expected by chance alone. Our results provide a potential explanation for the ubiquity of cooperative interactions in nature despite the known negative effects of cooperation on community stability.

With increasing incidence of drug resistance and toxicity associated with current treatments, new alternatives are needed for Candida albicans infections. This study evaluated the potential of Urtica dioica aqueous extract and essential oil as natural phytotherapeutic agents against C. albicans, with a focus on important virulence factors that contribute to the development of infection and survival in the host. Our findings demonstrate that U. dioica essential oil effectively suppressed the growth of C. albicans and exhibited synergistic activity with amphotericin B, suggesting that it could reduce the effective dose of amphotericin B required, and possibly limit its undesirable side effects. Significant and notable inhibition of phenotypic switching was also observed, with the most pronounced effects seen when used in combination with amphotericin B. Since hyphae are critical for host invasion, this inhibition could impede the ability of C. albicans to cause disseminated infections. In addition, U. dioica essential oil also inhibited the biofilm-forming ability of C. albicans, a key factor contributing to the morbidity and mortality of hospitalized patients, due to biofilm-related resistance to antimicrobial therapy. Complete inhibition of phospholipase and hemolysin activity was also observed; as key extracellular enzymes, these contribute to the virulence of C. albicans and its persistence in the host. In conclusion, U. dioica essential oil targets multiple C. albicans virulence factors, potentially limiting infection in vivo. When used in combination with amphotericin B, it may boost antifungal efficiency, offering a promising new strategy against candidiasis.

Quorum sensing (QS) is a critical communication system in bacteria that enables them to sense population density through auto-inducers, notably, N-acyl homoserine lactones (AHLs). This study focuses on the role of QS in Vibrio parahaemolyticus, a significant pathogen affecting vannamei shrimp, where it regulates virulence factors such as hemolysins and biofilm formation. We explored the potential of anti-QS agents derived from a Psychrobacter sp., which produces AHL lactonase capable of degrading AHLs and disrupting QS signaling pathways. The purification of AHL lactonase was achieved through chromatographic techniques, yielding a protein with a molecular weight of 28-30 kDa, consistent with previous findings. AHL degradation tests have demonstrated that AHL lactonase was significantly more effective than metabolites from Psychrobacter in breaking down AHLs. However, the metabolites exhibited superior biofilm inhibition activity, indicating distinct mechanisms in disrupting bacterial adherence and virulence. Gene expression analysis revealed that AHL lactonase effectively suppressed virulence-related genes, while the metabolites influenced gene regulation differently. This study highlights the dual mechanisms of action from a Psychrobacter sp. - direct AHL degradation and inhibition of AHL synthesis, offering a promising biocontrol strategy against V. parahaemolyticus infections in shrimp aquaculture. These findings suggest that integrating these approaches could enhance pathogen management, ultimately supporting sustainable aquaculture practices. Further research is warranted to elucidate the underlying molecular mechanisms and optimize the application of these biocontrol agents in disease management.

Chloroquine (CQ) is a 4-aminoquinoline that has historically been used as an anti-malarial drug. It has also been used to treat several autoimmune diseases, cancers, and viral infections. Most of the effects of CQ are mediated through its ability to accumulate in acidic vacuoles and increase their pH. However, at high doses, CQ is known to have various toxic effects, including ocular, retinal, neuromuscular, renal, and cardiac toxicities. The host responses involved in counteracting CQ toxicity remain poorly characterized. Here, using the Caenorhabditis elegans model, we characterize the host pathways that protect against CQ toxicity. Transcriptomics studies reveal that CQ exposure results in the upregulation of innate immune response and endoplasmic reticulum (ER) unfolded protein response (UPR) pathways. An analysis of multiple immune pathway mutants shows that different immune pathways defend against CQ toxicity. Intriguingly, some of these pathways, which converge to defend against pathogenic bacteria, operate independently to protect against CQ toxicity. Finally, we demonstrate that the ER-UPR pathways also play a crucial role in counteracting CQ toxicity.

Prenatal protein deficiency causes behavioral and cognitive dysfunctions in children. The deficits could be caused by altered acquisition and processing of sensory information in the brain. Although GABAergic neurons are the key regulators of neuronal activity, the effect of prenatal protein deficiency on GABA neurons in the brain is largely unknown. We fed pregnant mice diets with one-third (7%) or half (10%) the normal protein requirement (20% protein). After birth, the pups were fostered with normally fed lactating females. We used transgenic mice to show that protein deficiency in pregnant dams fed a 7% protein diet affected the number and distribution of GABA neurons in the somatosensory barrel cortex and individual cortical layers during early postnatal development of pups. If the mothers were fed a 10% protein diet, the effects on GABA neurons were much less. Development of barrels was also affected in pups born to mothers fed the 7% protein diet, but not the 10% group. In addition, high protein deficiency, i.e., the 7% protein diet, affected conception, hampered gestational weight gain, induced resorption of embryos, reduced litter sizes, and increased cannibalism, which was not observed in females on 10% protein diet.

The switch in the predominantly expressed transcript isoform of the same gene has been identified as a significant factor in the progression of various types of cancer. These switches can impact the gain or loss of different 3'UTRs, which are hotspots for the binding of microRNAs (miRNAs) and RNA-binding proteins (RBPs). In this study, we found that in cancer-specific dominant expressing transcripts, the binding of miRNA and RBP is disrupted, suggesting that transcript switching could play a part in modulating post-transcriptional gene expression during the progression and development of cancer. Our spatial correlation analysis demonstrated that changes in miRNA and RBP binding, triggered by transcript switching, could interrupt their interplay. Additionally, statistical analysis revealed that local folding energy (LFE) is a key factor in changing miRNA and RBP interactions due to isoform switching. Overall, this study revealed that changes in cancerspecific transcripts could influence miRNA-RBP interactions due to alternations in the local RNA structure of the transcript caused by isoform switching, thereby leading to the dysregulation of crucial genes involved in the evolution and progression of cancer.