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Fluids and Barriers of the CNS Dec 2023The lack of accessible and informative biomarkers results in a delayed diagnosis of Parkinson's disease (PD), whose symptoms appear when a significant number of...
BACKGROUND
The lack of accessible and informative biomarkers results in a delayed diagnosis of Parkinson's disease (PD), whose symptoms appear when a significant number of dopaminergic neurons have already disappeared. The retina, a historically overlooked part of the central nervous system (CNS), has gained recent attention. It has been discovered that the composition of cerebrospinal fluid influences the aqueous humor composition through microfluidic circulation. In addition, alterations found in the brain of patients with PD have a correlate in the retina. This new paradigm highlights the potential of the aqueous humor as a sample for identifying differentially concentrated metabolites that could, eventually, become biomarkers if also found altered in blood or CSF of patients. In this research we aim at analyzing the composition of the aqueous humor from healthy controls and PD patients.
METHODS
A targeted metabolomics approach with concentration determination by mass spectrometry was used. Statistical methods including principal component analysis and linear discriminants were used to select differentially concentrated metabolites that allow distinguishing patients from controls.
RESULTS
In this first metabolomics study in the aqueous humor of PD patients, elevated levels of 16 compounds were found; molecules differentially concentrated grouped into biogenic amines, amino acids, and acylcarnitines. A biogenic amine, putrescine, alone could be a metabolite capable of differentiating between PD and control samples. The altered levels of the metabolites were correlated, suggesting that the elevations stem from a common mechanism involving arginine metabolism.
CONCLUSIONS
A combination of three metabolites, putrescine, tyrosine, and carnitine was able to correctly classify healthy participants from PD patients. Altered metabolite levels suggest altered arginine metabolism. The pattern of metabolomic disturbances was not due to the levodopa-based dopamine replacement medication because one of the patients was not yet taking levodopa but a dopamine receptor agonist.
Topics: Humans; Parkinson Disease; Levodopa; Aqueous Humor; Putrescine; Biomarkers; Arginine
PubMed: 38049870
DOI: 10.1186/s12987-023-00494-5 -
International Journal of Biomaterials 2023Bacterial biofilm is a significant virulence factor threatening patients, leading to chronic infections and economic burdens. Therefore, it is crucial to identify...
BACKGROUND
Bacterial biofilm is a significant virulence factor threatening patients, leading to chronic infections and economic burdens. Therefore, it is crucial to identify biofilm production, its inhibition, and reduction. In this study, we investigated biofilm production among Gram-negative isolates and assessed the inhibitory and reduction potential of ethylene diamine tetra acetic acid (EDTA) and dimethyl sulfoxide (DMSO) towards them. In addition, we studied the antimicrobial resistance pattern of the Gram-negative isolates.
METHODS
Bacterial isolation and identification was done using standard microbiological techniques, following the Clinical and Laboratory Standards Institute (CLSI) guideline, 28th edition. The Kirby-Bauer disk diffusion method was used to determine the antibiotic susceptibility pattern of the isolates, and -lactamase production was tested via the combination disk method. Biofilm formation was detected through the tissue culture plate (TCP) method. Different concentrations of EDTA and DMSO were used to determine their inhibitory and reduction properties against the biofilm. Both inhibition and reduction by the various concentrations of EDTA and DMSO were analyzed using paired -tests.
RESULTS
Among the 110 clinical isolates, 61.8% (68) were found to be multidrug resistant (MDR). 30% (33/110) of the isolates were extended-spectrum -lactamase (ESBL) producers, 14.5% (16/110) were metallo--lactamase (MBL), and 8% (9/110) were carbapenemase (KPC) producers. Biofilm formation was detected in 35.4% of the isolates. Biofilm-producing organisms showed the highest resistance to antibiotics such as cephalosporins, chloramphenicol, gentamicin, and carbapenem. The inhibition and reduction of biofilm were significantly lower ( < 0.05) for 1 mM of EDTA and 2% of DMSO.
CONCLUSION
Isolates forming biofilm had a higher resistance rate and -lactamase production compared to biofilm nonproducers. EDTA and DMSO were found to be potential antibiofilm agents. Hence, EDTA and DMSO might be an effective antibiofilm agent to control biofilm-associated infections.
PubMed: 38023107
DOI: 10.1155/2023/6619268 -
Cell Communication and Signaling : CCS Feb 2024Inherited retinal degenerations (IRDs) are a group of untreatable and commonly blinding diseases characterized by progressive photoreceptor loss. IRD pathology has been...
Inherited retinal degenerations (IRDs) are a group of untreatable and commonly blinding diseases characterized by progressive photoreceptor loss. IRD pathology has been linked to an excessive activation of cyclic nucleotide-gated channels (CNGC) leading to Na- and Ca-influx, subsequent activation of voltage-gated Ca-channels (VGCC), and further Ca influx. However, a connection between excessive Ca influx and photoreceptor loss has yet to be proven.Here, we used whole-retina and single-cell RNA-sequencing to compare gene expression between the rd1 mouse model for IRD and wild-type (wt) mice. Differentially expressed genes indicated links to several Ca-signalling related pathways. To explore these, rd1 and wt organotypic retinal explant cultures were treated with the intracellular Ca-chelator BAPTA-AM or inhibitors of different Ca-permeable channels, including CNGC, L-type VGCC, T-type VGCC, Ca-release-activated channel (CRAC), and Na/Ca exchanger (NCX). Moreover, we employed the novel compound NA-184 to selectively inhibit the Ca-dependent protease calpain-2. Effects on the retinal activity of poly(ADP-ribose) polymerase (PARP), sirtuin-type histone-deacetylase, calpains, as well as on activation of calpain-1, and - 2 were monitored, cell death was assessed via the TUNEL assay.While rd1 photoreceptor cell death was reduced by BAPTA-AM, Ca-channel blockers had divergent effects: While inhibition of T-type VGCC and NCX promoted survival, blocking CNGCs and CRACs did not. The treatment-related activity patterns of calpains and PARPs corresponded to the extent of cell death. Remarkably, sirtuin activity and calpain-1 activation were linked to photoreceptor protection, while calpain-2 activity was related to degeneration. In support of this finding, the calpain-2 inhibitor NA-184 protected rd1 photoreceptors.These results suggest that Ca overload in rd1 photoreceptors may be triggered by T-type VGCCs and NCX. High Ca-levels likely suppress protective activity of calpain-1 and promote retinal degeneration via activation of calpain-2. Overall, our study details the complexity of Ca-signalling in photoreceptors and emphasizes the importance of targeting degenerative processes specifically to achieve a therapeutic benefit for IRDs. Video Abstract.
Topics: Mice; Animals; Retinal Degeneration; Calpain; Sodium-Calcium Exchanger; Photoreceptor Cells; Cell Death; Sirtuins; Egtazic Acid
PubMed: 38303059
DOI: 10.1186/s12964-023-01391-y -
International Dental Journal Jun 2024Dental caries is a widespread oral health issue in Asia, affecting an estimated 30% to 90% of children and adults. Many caries cases remain untreated, resulting in pain... (Review)
Review
Dental caries is a widespread oral health issue in Asia, affecting an estimated 30% to 90% of children and adults. Many caries cases remain untreated, resulting in pain and infection. In response, the Asian Academy of Preventive Dentistry (AAPD) emphasises comprehensive caries management and organised a fluoride workshop at the 15th International Conference of the AAPD in 2023. The AAPD invited a group of experts to form a fluoride working group to review existing literature and develop fluoride recommendations for stakeholders across Asian countries and regions. The working group assessed caries risk and identified commonly used topical fluoride products for home care, professional, and community settings in Asia. The working group concluded that fluoride is a safe and highly effective strategy to reduce caries prevalence and incidence. The working group provided key recommendations based on successful regional caries management practices: (1) use topical fluoride for prevention and control of dental caries; (2) encourage the use of fluoride toothpaste with a concentration of at least 1,000 ppm for effective caries reduction; (3) advise a 0.05% fluoride mouth rinse as soon as children can spit it out to prevent early childhood caries; (4) deliver professionally administered fluoride, such as 5% sodium fluoride varnish, 2% fluoride gel, or 1.23% acidulated phosphate fluoride preparations, to decrease dental caries in at-risk individuals; and (5) apply 38% silver diamine fluoride to arrest cavitated caries. These recommendations aim to help practitioners, health care providers, and parents/caregivers make informed decisions about fluoride use as part of comprehensive oral health care in the region.
PubMed: 38871599
DOI: 10.1016/j.identj.2024.04.016 -
Journal of the American Chemical Society Aug 2023Diamine-appended Mg(dobpdc) (dobpdc = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) metal-organic frameworks have emerged as promising candidates for carbon capture owing to...
Diamine-appended Mg(dobpdc) (dobpdc = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) metal-organic frameworks have emerged as promising candidates for carbon capture owing to their exceptional CO selectivities, high separation capacities, and step-shaped adsorption profiles, which arise from a unique cooperative adsorption mechanism resulting in the formation of ammonium carbamate chains. Materials appended with ,-diamines featuring bulky substituents, in particular, exhibit excellent stabilities and CO adsorption properties. However, these frameworks display double-step adsorption behavior arising from steric repulsion between ammonium carbamates, which ultimately results in increased regeneration energies. Herein, we report frameworks of the type diamine-Mg(olz) (olz = ()-5,5'-(diazene-1,2-diyl)bis(2-oxidobenzoate)) that feature diverse diamines with bulky substituents and display desirable single-step CO adsorption across a wide range of pressures and temperatures. Analysis of CO adsorption data reveals that the basicity of the pore-dwelling amine─in addition to its steric bulk─is an important factor influencing adsorption step pressure; furthermore, the amine steric bulk is found to be inversely correlated with the degree of cooperativity in CO uptake. One material, ee-2-Mg(olz) (ee-2 = ,-diethylethylenediamine), adsorbs >90% of the CO from a simulated coal flue stream and exhibits exceptional thermal and oxidative stability over the course of extensive adsorption/desorption cycling, placing it among top-performing adsorbents to date for CO capture from a coal flue gas. Spectroscopic characterization and van der Waals-corrected density functional theory calculations indicate that diamine-Mg(olz) materials capture CO via the formation of ammonium carbamate chains. These results point more broadly to the opportunity for fundamentally advancing materials in this class through judicious design.
PubMed: 37493594
DOI: 10.1021/jacs.3c03870 -
Antioxidants (Basel, Switzerland) Aug 2023Singapore grouper iridovirus (SGIV) is a new ranavirus species in the Iridoviridae family, whose high lethality and rapid spread have resulted in enormous economic...
Singapore grouper iridovirus (SGIV) is a new ranavirus species in the Iridoviridae family, whose high lethality and rapid spread have resulted in enormous economic losses for the aquaculture industry. Curcumin, a polyphenolic compound, has been proven to possess multiple biological activities, including antibacterial, antioxidant, and antiviral properties. This study was conducted to determine whether curcumin protected orange-spotted grouper () from SGIV-induced intestinal damage by affecting the inflammatory response, cell apoptosis, oxidative stress, and intestinal microbiota. Random distribution of healthy orange-spotted groupers (8.0 ± 1.0 cm and 9.0 ± 1.0 g) into six experimental groups (each group with 90 groupers): Control, DMSO, curcumin, SGIV, DMSO + SGIV, and curcumin + SGIV. The fish administered gavage received DMSO dilution solution or 640 mg/L curcumin every day for 15 days and then were injected intraperitoneally with SGIV 24 h after the last gavage. When more than half of the groupers in the SGIV group perished, samples from each group were collected for intestinal health evaluation. Our results showed that curcumin significantly alleviated intestine damage and repaired intestinal barrier dysfunction, which was identified by decreased intestine permeability and serum diamine oxidase (DAO) activity and increased expressions of tight junction proteins during SGIV infection. Moreover, curcumin treatment suppressed intestinal cells apoptosis and inflammatory response caused by SGIV and protected intestinal cells from oxidative injury by enhancing the activity of antioxidant enzymes, which was related to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Moreover, we found that curcumin treatment restored the disruption of the intestinal microbiota caused by SGIV infection. Our study provided a theoretical basis for the functional development of curcumin in aquaculture by highlighting the protective effect of curcumin against SGIV-induced intestinal injury.
PubMed: 37627579
DOI: 10.3390/antiox12081584 -
Journal of Inflammation Research 2023Intestinal ischemia/reperfusion (I/R) injury is a challenging pathological phenomenon accountable for significant mortality in clinical scenarios. Substantial evidence...
Esculetin Alleviates Inflammation, Oxidative Stress and Apoptosis in Intestinal Ischemia/Reperfusion Injury via Targeting SIRT3/AMPK/mTOR Signaling and Regulating Autophagy.
AIM
Intestinal ischemia/reperfusion (I/R) injury is a challenging pathological phenomenon accountable for significant mortality in clinical scenarios. Substantial evidence has supported the protective role of esculetin in myocardial I/R injury. This study is designed to reveal the specific impacts of esculetin on intestinal I/R injury and disclose the underlying mechanism.
METHODS
First, intestinal I/R injury model and intestinal epithelial cell line hypoxia/reoxygenation (H/R) model were established. Pathologic damages to intestinal tissues were observed through H&E staining. Serum diamine oxidase (DAO) levels were examined. RT-qPCR and Western blot examined the expression of inflammatory mediators. Commercial kits were used for detecting the levels of oxidative stress markers. TUNEL assay and caspase 3 activity assay measured cell apoptosis. Immunofluorescence (IF) staining measured autophagy levels. Western blot analyzed the expression of apoptosis-, Sirtuin 3 (SIRT3)/AMP activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling- and autophagy-related proteins. Molecular docking verified the interaction of esculetin with SIRT3. Cell viability was explored via CCK-8 assay.
RESULTS
The experimental results revealed that esculetin treatment mitigated pathological damage of intestinal tissues, reduced serum DAO level, ameliorated inflammation, oxidative stress and apoptosis and promoted autophagy in intestinal I/R rats. Moreover, esculetin bond to SIRT3 and activated SIRT3/AMPK/mTOR signaling both in vitro and in vivo. Furthermore, esculetin treatment enhanced cell viability and SIRT3 silencing reversed the impacts of esculetin on autophagy, inflammation, oxidative stress and apoptosis in H/R cell model.
CONCLUSION
In a word, esculetin activated SIRT3/AMPK/mTOR signaling and autophagy to protect against inflammation, oxidative stress and apoptosis in intestinal I/R injury.
PubMed: 37641705
DOI: 10.2147/JIR.S413941 -
European Endodontic Journal Jan 2024The aim of this in vitro study was to compare the smear layer and debris removal and antimicrobial activity of two dual-action irrigating solutions for continuous...
OBJECTIVE
The aim of this in vitro study was to compare the smear layer and debris removal and antimicrobial activity of two dual-action irrigating solutions for continuous chelation (Triton; Brasseler, Savannah, USA and Dual Rinse HEDP; Medcem GmbH, Weinfelden, Switzerland) with a dual step irrigation protocol with sodium hypochlorite (NaOCl) followed by ethylenediaminetetraacetic acid (EDTA).
METHODS
Thirty single-rooted single-canal teeth were divided into three groups (n=10) and irrigated with Triton, Dual Rinse HEDP mixed with 6% NaOCl and 6% NaOCl/17% EDTA. The teeth were observed under a scanning electron microscope (SEM) to assess the canal wall cleanliness. In addition, 80 dentine discs were contaminated with Candida albicans and 80 discs with Enterococcus faecalis and irrigated with Triton, Dual Rinse HEDP mixed with 6% NaOCl and 6% NaOCl/17% EDTA or not treated (n=20). Fifteen discs were used to evaluate colony-forming units, while 5 discs were analysed by SEM. Data were analysed using the Shapiro- Wilk, Kruskal-Wallis and One-Way ANOVA tests.
RESULTS
Triton was statistically more effective than Dual Rinse HEDP and NaOCl/EDTA in removing debris (p<0.05), except with NaOCl/EDTA in the coronal third. Triton was more effective than Dual Rinse HEDP in removing the smear layer from the apical and middle thirds (p<0.05). All the irrigation protocols significantly re- duced the number of E. faecalis. The Triton group showed the lowest number of remaining C. albicans (p<0.05).
CONCLUSION
Triton was the most effective irrigation solution in removing debris and as effective as NaOCl/ EDTA in removing the smear layer. Triton showed the highest efficacy against C. albicans. New irrigating solutions that provide continuous chelation may provide an alternative to current irrigation protocols.
Topics: Humans; Edetic Acid; Smear Layer; Etidronic Acid; Microscopy, Electron, Scanning; Dental Pulp Cavity; Root Canal Preparation; Root Canal Irrigants; Chelating Agents; Anti-Infective Agents
PubMed: 37965676
DOI: 10.14744/eej.2023.19042 -
Journal of Dairy Science Dec 2023l-Glutamine supplementation improves gastrointestinal and immune function in dairy calves during controlled immune and stress challenges. However, it is unknown whether...
l-Glutamine supplementation improves gastrointestinal and immune function in dairy calves during controlled immune and stress challenges. However, it is unknown whether supplementing milk replacer (MR) with l-glutamine improves preweaning dairy calf health and welfare under production conditions. Therefore, the study objective was to evaluate the effects of supplementing MR with l-glutamine on gastrointestinal permeability, immune function, growth performance, postabsorptive metabolic biomarkers, and physiological stress response in preweaning dairy calves. In 3 repetitions, Holstein heifer calves (n = 30; 1.5 ± 0.5 d old; 37.1 ± 0.86 kg body weight) were blocked by serum total protein, body weight, and age, and provided MR (3.8 L/calf per d; 24% CP, 17% fat, 12.5% solids) supplemented with l-glutamine (GLN; 10g/kg MR powder; n = 5 calves/repetition) or nonsupplemented (NSMR; n = 5 calves/repetition). Calves were individually housed with ad libitum starter grain and water access until weaning (56.4 ± 0.5 d old). At 1 and 6 wk of age, urinary catheters were placed, and calves were orally dosed with 1 L of chromium (Cr)-EDTA. Urine samples were collected over a 24-h period for Cr output analysis as an in vivo biomarker of gastrointestinal permeability. Blood was collected on study d 1, 5, 7, 14, 21, 42, and 56 to measure white blood cell counts, cortisol, insulin, glucose, nonesterified fatty acids, serum amyloid A, haptoglobin, and neutrophil: lymphocytes. Two study intervals were used in the statistical analyses, representing greater (P1; wk 1-3) and reduced (P2; wk 4-8) enteric disease susceptibility. Data were analyzed using PROC GLIMMIX in SAS 9.4 (SAS Institute Inc.) with calf as the experimental unit. Overall, total urinary Cr output was reduced in GLN versus NSMR calves. Total Cr output was reduced at 1 wk of age in GLN versus NSMR calves, but no differences were detected at 6 wk of age. Neutrophil:lymphocyte was decreased both overall and during P2 in GLN versus NSMR calves, and neutrophil counts tended to be reduced in GLN versus NSMR calves during P2. No MR treatment differences were detected for average daily feed intake, average daily gain, body measurements, postabsorptive metabolic biomarkers, disease scores, and therapeutic treatments between GLN and NSMR calves. In summary, l-glutamine supplementation reduced gastrointestinal permeability and biomarkers of physiological stress in preweaning Holstein heifer calves.
Topics: Animals; Cattle; Female; Diet; Glutamine; Weaning; Dietary Supplements; Body Weight; Milk; Stress, Physiological; Animal Feed; Biomarkers; Edetic Acid
PubMed: 37641349
DOI: 10.3168/jds.2023-23334 -
The Journal of Organic Chemistry Aug 20231,3-Diamine-derived catalysts were designed, synthesized, and used in asymmetric Mannich reactions of ketones. The reactions catalyzed by one of the 1,3-diamine...
1,3-Diamine-derived catalysts were designed, synthesized, and used in asymmetric Mannich reactions of ketones. The reactions catalyzed by one of the 1,3-diamine derivatives in the presence of acids afforded the Mannich products with high enantioselectivities under mild conditions. In most cases, bond formation occurred at the less-substituted α-position of the ketone carbonyl group. Our results indicate that the primary and the tertiary amines of the 1,3-diamine derivative cooperatively act for the catalysis.
PubMed: 37460110
DOI: 10.1021/acs.joc.3c01051