Enzyme Levels Research Articles

Effect of Bee Bread (Perga) on Histopathological Changes and Immunohistochemical Expression of Apoptosis Markers in the Kidney of Rats Exposed to Cadmium

Cadmium (Cd) is an environmental and industrial pollutant that causes toxicity in various organs in humans and animals. Bee bread (perga) is a natural flavonoid with a wide range of pharmacological properties. This study was conducted to examine the effects of perga on Cd-induced nephrotoxicity. Thirty-two male Wistar rats were randomly divided into 4 groups, as the Control group, Cd group (5 mg/kg/day, orally), Perga group (0.5 g/kg/day, orally), and Cd + Perga group. At the end of the 28-day experiment, kidney tissue samples were taken and histopathological, immunohistochemical, and biochemical analyses were performed. Histopathologically, severe tubular and glomerular damage occurred as a result of Cd exposure in the Cd group. Immunohistochemically, there was an increase in caspas-3 and Bax expression in the renal tissue in the Cd group. According to the biochemical results, while the catalase, superoxide dismutase, and glutathione peroxidase antioxidant enzyme levels decreased in the Cd group, and the malondialdehyde levels increased. However, most of the above-mentioned Cd-induced changes were attenuated by treatment with perga in the Perga + Cd group. In conclusion, perga supplementation may alleviate Cd-induced renal injury through inhibition of apoptosis in renal tissue.

Preliminary Investigation Into the Antidepressant Effects of a Novel Curcumin Analogue (CACN136) In Vitro and In Vivo.

The aim of this study was to develop a novel antidepressant with high activity. Based on the findings of molecular docking, eight novel curcumin analogues were evaluated in vitro to check for antidepressant efficacy. Among them, CACN136 had the strongest antidepressant effect. Firstly, CACN136 had a stronger 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate) radical ion scavenging ability (IC50: 17.500 ± 0.267μg/mL) compared to ascorbic acid (IC50: 38.858 ± 0.263μg/mL) and curcumin (27.189 ± 0.192μg/mL). Secondly, only CACN136 demonstrated clear protective effects on cells damaged by glutamate and oxidative stress at all concentrations. Finally, only CACN136 showed ASP + inhibition and was more effective than fluoxetine hydrochloride (FLU) at low concentrations. To further confirm the antidepressant effect of CACN136 in vivo, the CUMS model was established. Following 28days of oral administration of CUMS mice, CACN136 increased the central area residence time in the open-field test, significantly increased the sucrose preference rate in the sucrose preference test (P < 0.001) and significantly reduced the immobility period in the tail suspension test (P < 0.0001), all of which were more effective than those of FLU. Subsequent research indicated that the antidepressant properties of CACN136 were linked to a decrease in the metabolism of5-HT and the modulation of oxidative stress levels in vivo. In particular, the activation of the Keap1-Nrf2/BDNF-TrkB signaling pathway by CACN136 resulted in elevated levels of antioxidant enzymes, enhancing the antioxidant capability in mice subjected to CUMS. In conclusion, CACN136 has the potential to treat depression and could be an effective antidepressant.

Application of Coincidence Index in the Discovery of Co-Expressed Metabolic Pathways.

Analyzing transcription data requires intensive statistical analysis to obtain useful biological information and knowledge. A significant portion of this data is affected by random noise or even noise intrinsic to the modeling of the experiment. Without robust treatment, the data might not be explored thoroughly, and incorrect conclusions could be drawn. Examining the correlation between gene expression profiles is one way bioinformaticians extract information from transcriptomic experiments. However, the correlation measurements traditionally used have worrisome shortcomings that need to be addressed. This paper compares five already published and experimented with correlation measurements to the newly developed coincidence index, a similarity measurement that combines Jaccard and interiority indexes and generalizes them to be applied to vectors containing real values. We used microarray and RNA-Seq data from the archaeon Halobacterium salinarum and the bacterium Escherichia coli, respectively, to evaluate the capacity of each correlation/similarity measurement. The utilized method explores the co-expressed metabolic pathways by measuring the correlations between the expression levels of enzymes that share metabolites, represented in the form of a weighted graph. It then searches for local maxima in this graph using a simulated annealing algorithm. We demonstrate that the coincidence index extracts larger, more comprehensive, and more statistically significant pathways for microarray experiments. In RNA-Seq experiments, the results are more limited, but the coincidence index managed the largest percentage of significant components in the graph.

Control of Sitophilus oryzae (L.) using argon and helium atmospheric non-thermal plasma

The rice weevil, Sitophilus oryzae Linnaeus, 1763 (Coleoptera: Curculionidae), is a major pest of stored cereals worldwide that causes significant grain loss by feeding internally on seeds. In this study, we propose the use of an atmospheric pressure cold plasma generated from dielectric barrier discharge (DBD) as an emerging technology in insect pest management. Series of experiments were conducted to test the effectiveness of such plasmas on the lethality of adult S. oryzae by measuring the mortality rate and examining the biochemical markers that impact the insects. Plasma treatments (24 kV input voltage at frequency of 2.5 or 7.5 kHz) were carried out in He and Ar, used as carrier gases, with exposure time ranging from 30 to 120 s. Results showed a high level of mortality (60–100%) for each treatment, with a better efficiency observed when Ar was used as carrier gas. Furthermore, at the highest repetition frequency (7.5 kHz), equivalent to 60 W of electrical power consumption, the insecticidal efficiency reached 100% insect mortality at only 1 h after a 30 s plasma treatment. The mortality rate appeared to be correlated with a notable decrease in protein content and an increase in catalase enzyme levels within the insects' tissue, indicating that insecticidal mechanisms involve oxidative stress. This study demonstrates that low-energy atmospheric cold plasma has detrimental effects on rice weevils and could be considered a promising tool for pest control in stored food, which will help reduce global dependence on chemical pesticides.

Investigating the relationship between shift work schedule and blood and metabolic parameters: a 10-years retrospective cohort study

Shift work has become increasingly common in modern society. Shift work has been associated with a range of negative health outcomes. Therefore, this 10-years retrospective cohort study, aimed to investigate the relationship between shift work and blood and metabolic parameters. This retrospective cohort study was conducted in a metal parts manufacturing industry in 2023. In this study, 204 shift workers and 204 day workers were examined. All the studied blood and metabolic parameters were collected by reviewing the medical records of all participants during a 10-years period (2013–2022). Moreover, the amounts of physical, chemical, and ergonomics harmful agents in the work environment were investigated. All the collected data were analyzed using SPSS version 25.0. The values of Body Mass Index (BMI), Red Blood Cell Count (RBC), Platelets Count (PLT), Thyroid-Stimulating Hormone Level (TSH), Fasting Blood Sugar Level (FBS), Creatinine, Triglyceride (TG), Liver Enzymes level (SGOT and SGPT), and Systolic Blood Pressure (SBP) were higher among the shift work employees, and a significant difference was observed between the values of these parameters between the two groups. The results of logistic regression showed that the highest effect of shift work was observed on the parameters of FBS, TG, SGPT, TSH, Physical activity, BMI, Sleep duration, PLT, and Sleep quality with beta coefficient values of 0.49, 0.33, 0.29, 0.29, 0.20, 0.18, 0.14, 0.13 and, 0.11, respectively (p-value < 0.01). The present study contributes to a growing body of evidence that blood and metabolic factors are likely to be influenced by shift work. These findings have important implications for policy makers, highlighting the need for interventions to mitigate the negative health effects of shift work on workers.

Elucidating the biotechnological potential of the genera Parageobacillus and Saccharococcus through comparative genomic and pan-genome analysis

BackgroundThe genus Geobacillus and its associated taxa have been the focal point of numerous thermophilic biotechnological investigations, both at the whole cell and enzyme level. By contrast, comparatively little research has been done on its recently delineated sister genus, Parageobacillus. Here we performed pan-genomic analyses on a subset of publicly available Parageobacillus and Saccharococcus genomes to elucidate their biotechnological potential.ResultsPhylogenomic analysis delineated the compared taxa into two distinct genera, Parageobacillus and Saccharococcus, with P. caldoxylosilyticus isolates clustering with S. thermophilus in the latter genus. Both genera present open pan-genomes, with the species P. toebii being characterized with the highest novel gene accrual. Diversification of the two genera is driven through the variable presence of plasmids, bacteriophages and transposable elements. Both genera present a range of potentially biotechnologically relevant features, including a source of novel antimicrobials, thermostable enzymes including DNA-active enzymes, carbohydrate active enzymes, proteases, lipases and carboxylesterases. Furthermore, they present a number of metabolic pathways pertinent to degradation of complex hydrocarbons and xenobiotics and for green energy production.ConclusionsComparative genomic analyses of Parageobacillus and Saccharococcus suggest that taxa in both of these genera can serve as a rich source of biotechnologically and industrially relevant secondary metabolites, thermostable enzymes and metabolic pathways that warrant further investigation.

Reparative effects of Schizophyllum commune oat bran fermentation broth on UVB-induced skin inflammation via the JAK/STAT pathway

Human immortal keratinocyte cells (HaCaT) are induced with UVB to establish an injury model. This model is utilized to investigate whether oat bran fermentation broth (OBF) has a reparative effect on skin inflammation and damage to the skin barrier caused by UVB irradiation. The results show that compared with unfermented oat bran (OB), OBF exhibits higher structural homogeneity, increased molecular weight size, active substances content, and in vitro antioxidant activity. OBF has a scavenging effect on excess reactive oxygen species (ROS) and increases the intracellular levels of antioxidant enzymes. It was found that OBF has a stronger inhibitory effect on the release of inflammatory factors than OB. It increases the synthesis of AQP3 and FLG proteins while decreasing the secretion of KLK-7. OBF can inhibit the transcription level of inflammatory factors by suppressing the JAK/STAT signaling pathway. Safety experiments demonstrate that OBF has a high safety profile.Graphical

Diets containing phytobiotics, l-arginine, vitamin E and captopril modulate ascites syndrome-related genes expression in broiler chickens exposed to low ambient temperature.

Our hypothesis centred on the potential to mitigate ascites outbreaks in birds exposed to cold stress by inhibiting pulmonary artery contraction through dietary intervention. This study aimed to evaluate the effect of natural and synthetic medications on growth performance, ascites-related parameters and the expression of ascites-related genes in the lung tissue of broiler chickens under low ambient temperature. We randomly assigned 450 one-day-old male Ross 308 chicks to six dietary treatments across five replicate pens, each containing 15 chicks. The treatments included a basal diet (control), and the basal diet was supplemented with hydroalcoholic extracts of sumac (HES, 200mg/kg), Syrian mesquite (HEM, 200mg/kg), l-arginine (40% above requirement), captopril (15mg/kg) and vitamin E (100mg/kg). Diets containing HEM, l-arginine and vitamin E resulted in increased average daily gain on days 8-14 and 0-28, whereas HES showed a similar effect only during days 8-14 compared to the control diet (p<0.05). Additionally, feed additives decreased packed cell volume, left and right ventricle volumes and systolic blood pressure (p<0.05). Moreover, chickens fed the control and l-arginine diets exhibited higher levels of angiotensin converting enzyme (ACE) mRNA in lung tissue compared to those fed HES, HEM and captopril (p<0.05). Meanwhile, supplementation with HEM and l-arginine increased the expression of inducible nitric oxide synthase (iNOS) mRNA in lung tissue compared to other treatments (p<0.05). Regarding Cu/Zn-superoxide dismutase (Cu/Zn-SOD) expression, feed additives increased mRNA level in lung tissue, except for captopril (p<0.05). This study demonstrates that the plant extracts may reduce the incidence of ascites syndrome not only through their antioxidant properties but also by modulating the expression of ACE, iNOS and Cu/Zn-SOD genes.

Interleukin-18 binding protein regulates mast cell activation and mast cell induced osteoclastogenesis of rheumatoid arthritis.

Mast cell activation induces pathological responses, including increased osteoclastogenesis in rheumatoid arthritis (RA). Interleukin (IL)-18 binding protein (IL-18BP) has anti-inflammatory effects. In this study, we evaluated the effect of IL-18BP on mast cell activation and mast cell induced osteoclastogenesis. Mast cells were activated by IL-33 (100 ng/mL) and cultured with IL-18BP (10, 50, and 100 ng/mL). The proliferation, apoptosis, and necroptosis of mast cells were measured using flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of mast cell enzymes, matrix metalloproteinase (MMP), soluble RANKL (sRANKL), and pro-inflammatory cytokines in the culture media. Monocytes from patients with RA patients (n=5) were cultured with activated mast cells with various concentrations of IL-18BP. TRAP+ multinucleated osteoclasts, bone resorption area, and osteoclast differentiation-related genes were measured. Proliferation of tryptase+chymase+c-kit+FcεR1+ mast cells was suppressed following incubation with IL-18BP (10, 50, and 100 ng/mL). RNA expression levels of tryptase and chymase were reduced by 100 ng/mL IL-18BP. Additionally, the levels of MMP-3/9, IL-17A, IL-6, TNF-α, and sRANKL were significantly inhibited by 100 ng/mL IL-18BP. Annexin V+ and annexin V-PI+ mast cells were reduced following incubation with 100 ng/mL IL-18BP. The addition of IL-33 significantly stimulated mast cell and increased TRAP+ multinucleated cells and bone resorption area, and these effects were suppressed by IL-18BP. The osteoclast-related genes (TRAP, ATP6v0d2, RANK, and cathepsin K) expression were suppressed by IL-18BP. IL-18BP suppressed mast cell activation and mast cell induced osteoclastogenesis. This suggests a potential anti-arthritic role for IL-18BP in patients with RA.

Roles of Individual Human Cytochrome P450 Enzymes in Drug Metabolism.

Our knowledge of the roles of individual cytochrome P450 (P450, CYP) enzymes in drug metabolism has developed considerably in the past 30 years, and this base has been of considerable use in avoiding serious issues with drug interactions and issues due to variations. Some newer approaches are being considered for "phenotyping" of metabolism reactions with new drug candidates. Endogenous biomarkers are being used for non-invasive estimation of levels of individual P450 enzymes. There is also the matter of some remaining "orphan" P450s, which have yet to be assigned reactions. Practical problems that continue in drug development include predicting drug-drug interactions, predicting the effects of polymorphic and other P450 variations, and evaluating inter-species differences in drug metabolism, particularly in the context of "metabolism in safety testing" (MIST) regulatory issues ("disproportionate (human) metabolites"). Significance Statement Cytochrome P450 enzymes are the major catalysts involved in drug metabolism. The characterization of their individual roles has major implications in drug development and clinical practice.

Safety analysis of laboratory parameters in paediatric patients with spinal muscular atrophy treated with nusinersen

BackgroundSpinal muscular atrophy (SMA) is a progressive neurodegenerative disorder that can be treated with intrathecal nusinersen, an antisense oligonucleotide. In addition to efficacy, safety is a determining factor in the success of any therapy. Here, we aim to assess the safety of nusinersen therapy in paediatric patients with SMA.MethodsLaboratory data of paediatric patients with SMA who received nusinersen between October 2019 and May 2022 were retrospectively analysed.ResultsDuring the observation period, 46 infants and children aged 2.9 months to 13.6 years received a total of 213 nusinersen doses without safety concerns. Inflammatory markers were stable throughout the study. International normalized ratio was increased by 0.09 per injection. Urea levels were increased by 0.108 mmol/L, and cystatin C decreased by 0.029 mg/L per injection. There were no significant changes in platelet count, activated partial thrombin time, creatinine levels or liver enzyme levels during treatment. The cerebrospinal fluid (CSF) leukocyte count remained stable, and total protein increased by 24.038 mg/L per injection.ConclusionOur data showed that nusinersen therapy is generally safe in children with SMA. Laboratory monitoring did not identify any persistent or significantly abnormal findings. CSF protein should be monitored to gain more insights.

Mechanisms by which Mettl3 regulates pericyte-myofibroblast transdifferentiation through PI3K/AKT signaling pathway

Objective: To investigate the role and underlying mechanisms of methyltransferase (Mettl) 3 in the process of angiotensin Ⅱ (Ang Ⅱ)-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis. Methods: C57BL/6J mice were used, in cell experiments, mouse renal pericytes were isolated and cultured using magnetic bead sorting. These pericytes were then induced to transdifferentiate into myofibroblasts with 1×106 mmol/L Ang Ⅱ, which was the Ang Ⅱ group, while pericytes cultured in normal conditions served as the control group. Successful transdifferentiation was verified by immunofluorescence staining, Western blotting, and real-time reverse transcription PCR (RT-qPCR) for α-smooth muscle actin (α-SMA). The levels of m6A modifications and related enzymes (Mettl3, Mettl14), Wilms tumor 1-associated protein (WTAP), fat mass and obesity protein (FTO), ALKBH5, YTHDF1, YTHDF2, YTHDC1, YTHDC2, YTHDC3 were assessed by Dot blot, RT-qPCR and Western blot. Mettl3 expression was inhibited in cells using lentivirus-mediated Mettl3-shRNA transfection, creating sh-Mettl3 and Ang Ⅱ+sh-Mettl3 groups, while lentivirus empty vector transfection served as the negative control (Ang Ⅱ+sh-NC group). The impact of Ang Ⅱ on pericyte transdifferentiation was observed, and the expression of downstream phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway proteins, including PI3K, AKT, phosphorylated AKT at serine 473 (p-AKT (S473)), and phosphorylated AKT at threonine 308 (p-AKT (T308)), were examined. PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time. The reversibility of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was assessed by adding the AKT activator SC79 to the Ang Ⅱ+sh-Mettl3 group. In animal experiments, mice were divided into these groups: sham group (administered 0.9% sterile saline), Ang Ⅱ group (infused with Ang Ⅱ solution), sh-Mettl3 group (injected with Mettl3 shRNA lentivirus solution), Ang Ⅱ+sh-Mettl3 group (infused with Ang Ⅱ solution and injected with Mettl3 shRNA lentivirus solution), and Ang Ⅱ+sh-Mettl3+SC79 group (administered Ang Ⅱ solution and Mettl3 shRNA lentivirus, with an additional injection of SC79). Each group consisted of six subject mice. Blood pressure was measured using the tail-cuff method before and after surgery, and serum creatinine, urea, and urinary albumin levels were determined 4 weeks post-surgery. Kidney tissues were collected at 28 days and stained using hematoxylin-eosin (HE) and Masson's trichrome to assess the extent of renal fibrosis. Results: Primary renal pericytes were successfully obtained by magnetic bead sorting, and intervened with 1×106 mmol/L Ang Ⅱ for 48 hours to induce pericyte-to-myofibroblast transdifferentiation. Dot blot results indicated higher m6A modification levels in the Ang Ⅱ group compared to the control group (P<0.05). RT-qPCR and Western blot results showed upregulation of Mettl3 mRNA and protein levels in the Ang Ⅱ group compared to the control group (both P<0.05). In the Ang Ⅱ+sh-Mettl3 group, Mettl3 protein expression was lower than that in the Ang Ⅱ group, with reduced expression levels of α-SMA, vimentin, desmin, fibroblast agonist protein (FAPa) and type Ⅰ collagen (all P<0.05). Compared to the control group, PI3K mRNA expression level was elevated in the Ang Ⅱ group, along with increased p-AKT (S473) and p-AKT (T308) expressions. In the Ang Ⅱ+sh-Mettl3 group, PI3K mRNA expression and p-AKT (S473) and p-AKT (T308) levels were decreased (all P<0.05). The half-life of PI3K mRNA was shorter in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ+sh-NC group (2.34 h vs. 3.42 h). The ameliorative effect of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was reversible by SC79. Animal experiments showed higher blood pressure, serum creatinine, urea, and 24-hour urinary protein levels, and a larger fibrosis area in the Ang Ⅱ group compared to the sham group (all P<0.05). The fibrosis area was smaller in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ group (P<0.05), but increased again upon addition of SC79. Conclusion: Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.

A standardized chamuangone enriched extract from Garcinia cowa Roxb. leaves shows acute and sub-acute safety

Ethnopharmacological relevanceThe safety assessment of herbal products is critical for their appropriate pharmacological applications. Garcinia cowa Roxb., commonly known as Cha-muang in Thai, has ethnopharmacological relevance for inflammation, infectious diseases, and diabetes. The leaf extracts of G. cowa have been extensively reported for their anticancer, anti-inflammatory, antimicrobial, and antioxidant effects. Notably, chamuangone is their major active constituent that contributes to various pharmacological properties. Aim of the studyThe current study aims to establish a standardized chamuangone enriched extract (CEE) and assess its acute and sub-acute toxicities in animal models. MethodologyCEE was established from G. cowa leaves using a microwave-assisted extraction (MAE), followed by fractionation and enrichment through silica gel vacuum and column chromatography. The concentration of chamuangone in the extract was quantified using a validated quantitative high-performance liquid chromatography (HPLC) method. The safety profiles of CEE were thoroughly evaluated in rodents according to the Organization for Economic Cooperation and Development (OECD) 425 and 407 guidelines. The effects on oxidative stress markers such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) levels were also evaluated in various organs. ResultsBased on the quantitative HPLC analysis, the CEE contained 73.0 ± 2.0% w/w of chamuangone. In the acute toxicity study, following up and down procedure the female rats were dosed with CEE at 1750 and 550 mg/kg body weight (b.w.), with CEE 1750 mg/kg b.w. was toxic, causing mortality, while CEE 550 mg/kg b.w. was deemed safe. An LD50 value was calculated according to the standard protocols, resulting in 970 mg/kg b.w. In histopathological examination, 550 mg/kg b.w. of CEE was safe in all the selected organs, while the 1750 mg/kg b.w. CEE treated rats exhibited toxic effects in histological tissues sections in the form of necrosis in the brain, cardiac muscle hypertrophy, liver inflammation, mild untoward effect in the spleen, fibrosis in the lungs, pancreatitis, pyelonephritis, and ovarian cyst. Administration of CEE at doses of 550 mg/kg b.w. (single dose) in the acute and 100 mg/kg b.w. (regularly 28-days) in the sub-acute toxicity studies significantly (p < 0.05) decreased levels of uric acid, triglycerides, and cholesterol. Importantly, the CEE (550 and 100 mg/kg b.w.) also significantly increased the levels of antioxidant enzymes (SOD, GSH, and CAT) and decreased MDA levels. Normal histopathology was observed in the sub-acute toxicity study in all treated groups. ConclusionThis study successfully concludes that CEE at a dose of 100 mg/kg b.w. is safe for therapeutic application or use as a chemopreventive functional food utilizing green extraction methods. However, chronic toxicity studies are further recommended to validate safety concerns over an extended period.

Exploring the protective role of Bacillus velezensis BV1704–Y in zebrafish health and disease resistance against Aeromonas hydrophila infection

Bacillus genus, particularly Bacillus velezensis, is increasingly considered as viable alternatives to antibiotics in aquaculture due to their safety and probiotic potential. However, the specific mechanisms through which probiotic B. velezensis confers protection against Aeromonas hydrophila infection in fish remain poorly understood. This study delved into the multifaceted impacts of B. velezensis BV1704–Y on diverse facets of zebrafish health, including gut barrier function, immune response, oxidative stress, gut environment, microbiome composition, and disease resistance. Our findings demonstrate that supplementation with B. velezensis BV1704–Y significantly alleviated symptoms and reduced mortality in zebrafish infected with A. hydrophila.Furthermore, a notable reduction in the expression of pivotal immune-related genes, such as IL-1β, IL6, and TNF-α, was evident in the gut and head kidney of zebrafish upon infection. Moreover, B. velezensis BV1704–Y supplementation resulted in elevated activity levels of essential antioxidant enzymes, including SOD, CAT, and GSH, in gut tissue. Notably, B. velezensis BV1704–Y positively modulated the structure and function of the intestinal microbiome, potentially enhancing immune response and resilience in zebrafish. Specifically, supplementation with B. velezensis BV1704–Y promoted the relative abundance of beneficial bacteria, such as Cetobacterium, which showed a noteworthy negative correlation with the expression of pro-inflammatory genes and a positive correlation with gut barrier-related genes. Altogether, our study suggests that B. velezensis BV1704–Y holds promise as an effective probiotic for protecting zebrafish against A. hydrophila infection, offering potential benefits for the aquaculture industry.

Acute hepatotoxicity of intravenous amiodarone in a Becker muscular dystrophy patient with decompensated heart failing and ABCB4 gene mutation: as assessed for causality using the updated RUCAM

BackgroundCardiac dysfunction, including arrhythmias, may be one of the main clinical manifestations of Becker muscular dystrophy (BMD). Amiodarone is widely used to treat arrhythmia. However, multi-systemic toxicity caused by amiodarone, especially hepatotoxicity, should not be neglected. Here, we introduce a novel case of multi-systemic amiodarone toxicity involving the liver, renal and coagulation in BDM patient with ABCB4 gene mutation.Case presentationWe present a case of a 16-year-old boy admitted with heart failure and atrial fibrillation (AF). He was diagnosed with Becker muscular dystrophy (BMD) and gene testing showed comorbid mutations in gene DMD, ABCB4 and DSC2. Amiodarone was prescribed to control the paroxysmal atrial fibrillation intravenously. However, his liver enzyme levels were sharply elevated, along with cardiac shock, renal failure and coagulation disorders. After bedside continuous renal replacement therapy, the patient’s liver function and clinical status rehabilitated.ConclusionsABCB4 gene mutation might be involved in amiodarone-induced hepatotoxicity. Studies in a cohort might help to prove this hypothesis in the future.

Enzyme-Triggered Degradation of Supramolecularly Cross-Linked Polymersomes of Azobenzene-Based Polyurethane: Cell-Selective Anticancer Drug Release.

Enzyme-responsive self-assembled nanostructures for drug delivery applications have gained a lot of attention, as enzymes exhibit dysregulation in many disease-associated microenvironments. Azoreductase enzyme levels are strongly elevated in many tumor tissues; hence, here, we exploited the altered enzyme activity of the azoreductase enzyme and designed a main-chain azobenzene-based amphiphilic polyurethane, which self-assembles into a vesicular nanostructure and is programmed to disassemble in response to a specific enzyme, azoreductase, with the help of the nicotinamide adenine dinucleotide phosphate (NADPH) coenzyme in the hypoxic environment of solid tumors. The vesicular nanostructure sequesters, stabilizes the hydrophobic anticancer drug, and releases the drug in a controlled fashion in response to enzyme-triggered degradation of azo-bonds and disruption of vesicular assembly. The biological evaluation revealed tumor extracellular matrix pH-induced surface charge modulation, selective activated cellular uptake to azoreductase overexpressed lung cancer cells (A549), and the release of the anticancer drug followed by cell death. In contrast, the benign nature of the drug-loaded vesicular nanostructure toward normal cells (H9c2) suggested excellent cell specificity. We envision that the main-chain azobenzene-based polyurethane discussed in this manuscript could be considered as a possible selective chemotherapeutic cargo against the azoreductase overexpressed cancer cells while shielding the normal cells from off-target toxicity.

Non-linear association of liver enzymes with cognitive performance in the elderly: A cross-sectional study.

Although liver metabolic dysfunction has been found to potentially elevate susceptibility to cognitive impairment and dementia, there is still insufficient evidence to explore the non-linear association of liver enzymes with cognitive performance. Therefore, we aimed to elucidate the non-linear relationship between liver enzymes and cognitive performance. In this cross-sectional study, 2764 individuals aged ≥ 60 who participated in the National Health and Nutrition Survey (NHANES) between 2011 and 2014 were included. The primary data comprised liver enzyme levels (alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT ratio, and gamma-glutamyl transferase (GGT)), and cognitive performance was the major measured outcome. The associations were analyzed using weighted multivariate logistic regression, subgroup analysis, a generalized additive model, smooth fitting curves, and threshold effects. The results of the fully adjusted model indicated that ALP was negatively associated with the animal fluency test (AFT) score (OR = 1.48, 95% CI: 1.11-1.98), whereas ALT demonstrated a positive association with the consortium to establish a registry for Alzheimer's disease (CERAD) test score (OR = 0.72, 95% CI: 0.53-0.97). Additionally, the AST/ALT ratio was negatively associated with the global cognitive test (OR = 2.39, 95% CI: 1.53-3.73), CERAD (OR = 2.61, 95% CI: 1.77-3.84), and digit symbol substitution test (DSST) scores (OR = 2.51, 95% CI: 1.57-4.02). GGT was also negatively associated with the AFT score (OR = 1.16, 95% CI: 1.01-1.33) in unadjusted model. A non-linear relationship was observed between liver enzymes and the risk of cognitive impairment as assessed by the global cognitive test. Specifically, when ALP > 60 U/L, 0.77 < AST/ALT < 1.76, and 25 < GGT < 94 U/L, higher liver enzyme levels were significantly associated with an elevated cognitive impairment risk, while a lower cognitive impairment risk when ALT level was > 17 U/L. There is a non-linear relationship between liver enzymes and cognitive performance, indicating that liver enzyme levels should be maintained within a certain level to mitigate the risk of cognitive impairment.

Neuroprotective effect of sea urchins (Diadema savignyi) extract in an animal model of aluminum neurotoxicity

Human exposure to heavy metals causes major health consequences. Aluminum (Al) toxicity primarily affects the brain and has been implicated in neurodegenerative disorders. Natural products offer a cheap and safe source of protective agents against heavy metal toxicity. This study investigates the neuroprotective role of the shell extract (SH) from the Sea urchin (Diadema savignyi) collected from the Red Sea in an Aluminum-induced neurotoxicity model.Aluminum (Al, 250 µg/ml) caused cell death in a dose-dependent manner on neuroblastoma (SH-SY5Y) cells. The shell extract (50, 100, and 200 µg/ml) improved cell viability of the neuroblastoma cells. In vivo, toxicity assessment showed that Aluminum administration increased the levels of blood Urea, creatinine, and liver enzymes. Treatment with Shell extract reversed the levels back to normal.Oxidative stress assessment in vitro and in vivo showed that Al caused an increase in Nitric Oxide (NO) concentration and a significant reduction in Catalase and Glutathione (GSH) activity. Treatment with Shell extract (SH) improved these changes.Microscopic examination of the cerebral cortex showed that Aluminum-treated animals had significant neuronal damage, as evidenced by the degenerated neurons and increased apoptosis marker Caspase 3. There was also an increase in glial activation seen by an increase in the expression of Glial fibrillary Acidic Protein (GFAP). Treatment with Shell extract (100 and 200 µg/kg) showed neuroprotective effects all over cortical layers with minimal neuronal degenerative changes.The current work proves the potential antitoxic and neuroprotective properties of Sea Urchins (Diadema savignyi) extract as a cheap and safe therapeutic alternative against heavy metal toxicity.

Sesaminol alters phospholipid metabolism and alleviates obesity-induced NAFLD.

The prevalence of obesity-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance is increasing worldwide. We previously demonstrated that sesaminol increases thermogenesis in adipocytes, improves insulin sensitivity, and mitigates obesity in mice. In this study, we demonstrated that sesaminol increased mitochondrial activity and reduced ROS production in hepatocytes. Therefore, we delve into the metabolic action of sesaminol in obesity-induced NAFLD or metabolic dysfunction-associated liver disease (MAFLD). Here, we report that sesaminol induces OXPHOS proteins and mitochondrial function invivo. Further, our data suggest that sesaminol administration reduces hepatic triacylglycerol accumulation and LDL-C levels. Prominently, the lipidomics analyses revealed that sesaminol administration decreased the major phospholipids such as PC, PE, PI, CL, and PS to maintain membrane lipid homeostasis in the liver upon HFD challenge. Besides, SML reduced ePC and SM molecular species and increased PA levels in the HFD-fed mice. Also, sesaminol renders anti-inflammatory properties and dampens fibrosis markers in the liver. Remarkably, SML lowers the hepatic levels of ALT and AST enzymes and alleviates NAFLD in diet-induced obese mice. The molecular docking analysis identifies peroxisome proliferator-activated receptors as potential endogenous receptors for sesaminol. Together, our study demonstrates plant lignan sesaminol as a potential small molecule that alters the molecular species of major phospholipids, including sphingomyelin and ether-linked PCs in the liver tissue, improves metabolic parameters, and alleviates obesity-induced fatty liver disease in mice.

Hubungan Antara Pemeriksaan Antibodi IgG Dengan Uji SGOT SGPT Pada Pasien Demam Berdarah Dengue Di RSU Sinar Kasih Purwokerto

Dengue Hemorrhagic Fever (DHF) is a disease caused by infection with the dengue virus which is transmitted through the bite of the Aedes aegypti mosquito. The main clinical manifestations of this disease can be an increase in body temperature ≥ 38°C for 2 - 7 days, bleeding which is usually preceded by the appearance of red spots (petechiae), headache, joint pain accompanied by leukopenia, lymphadenopathy, thrombocytopenia and hemorrhagic diathesis. Liver dysfunction is one of the consequences of dengue infection that often occurs in patients. The liver is the target organ of the dengue virus which often appears in the form of hepatomegaly and a mild-moderate increase in aminotransferase enzyme levels although jaundice and acute liver failure are rare. Dengue patients have an increase in SGOT and SGPT levels. This study aims to determine whether there is a relationship between dengue IgG levels and SGOT and SGPT in Dengue Hemorrhagic Fever patients at RSU Sinar Kasih Purwokerto. The type of research used is an analytical study with a cross-sectional approach. Sampling was carried out using a consecutive sampling technique. Results were obtained from 100 samples with normal SGOT SGPT examination results, namely 10 patients and high results, namely 90 patients. The results of SGOT and SGPT examinations in dengue IgG positive patients increased &gt;3 times which was included in category B and there was a significant relationship between SGOT and SGPT levels in Dengue IgG positive patients, with a p-value of 0.000, indicating a strong relationship between SGOT levels and SGPT with IgG examination results.