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Molecular Pharmaceutics Jul 2024The aberrant assembly of amyloid-β (Aβ) is implicated in Alzheimer's disease (AD). Recent clinical outcomes of Aβ-targeted immunotherapy reinforce the notion that...
The aberrant assembly of amyloid-β (Aβ) is implicated in Alzheimer's disease (AD). Recent clinical outcomes of Aβ-targeted immunotherapy reinforce the notion that clearing Aβ burden is a potential therapeutic approach for AD. Herein, to develop drug candidates for chemically driven clearance of Aβ aggregates, we synthesized 51 novel polyfunctionalized furo[2,3-:4,5-']dipyridine-chalcone hybrid compounds. After conducting two types of cell-free anti-Aβ functional assays, Aβ aggregation prevention and Aβ aggregate clearance, we selected YIAD-0336, ()-8-((1-pyrrol-2-yl)methylene)-10-(4-chlorophenyl)-2,4-dimethyl-7,8-dihydropyrido[3',2':4,5]furo[3,2-]quinolin-9(6)-one, for further investigations. As YIAD-0336 exhibited a low blood-brain barrier penetration profile, it was injected along with aggregated Aβ directly into the intracerebroventricular region of ICR mice and ameliorated spatial memory in Y-maze tests. Next, YIAD-0336 was orally administered to 5XFAD transgenic mice with intravenous injections of mannitol, and YIAD-0336 significantly removed Aβ plaques from the brains of 5XFAD mice. Collectively, YIAD-0336 dissociated toxic aggregates in the mouse brain and hence alleviated cognitive deterioration. Our findings indicate that chemically driven clearance of Aβ aggregates is a promising therapeutic approach for AD.
Topics: Animals; Alzheimer Disease; Mice; Amyloid beta-Peptides; Disease Models, Animal; Mice, Transgenic; Chalcone; Chalcones; Male; Brain; Humans; Memory; Protein Aggregates; Blood-Brain Barrier; Maze Learning; Pyridines
PubMed: 38875185
DOI: 10.1021/acs.molpharmaceut.4c00068 -
Cureus May 2024In recent years, the quest for healthier alternatives to sugar has led to the widespread use of sugar alcohol in various food and beverage products. Sugar alcohols, such... (Review)
Review
In recent years, the quest for healthier alternatives to sugar has led to the widespread use of sugar alcohol in various food and beverage products. Sugar alcohols, such as xylitol, sorbitol, and erythritol, are popular substitutes due to their sweet taste and lower calorie content than sucrose. Beyond their role in calorie reduction, sugar alcohols have garnered attention for their potential impact on oral health. The bibliometric analysis of clinical trials on sugar alcohol and oral health in PubMed reveals a dynamic and multifaceted research landscape shaped by various factors. Fluctuations in publication rates over time suggest influences such as shifts in research interests, technological advancements, regulatory changes, and evolving consumer behaviors. Key authors like Makinen KK, Makinen PL, and Soderling E emerge as prolific contributors with collaborative solid networks within the research community. The University of Turku in Finland has been identified as the highest contributing university, while Caries Research is the most contributing journal based on the number of clinical trials published. The country-wise analysis highlights Italy and the United States as substantial contributors, with diverse trajectories of research activity observed across nations. The subject-specific words with the highest cooccurrence are xylitol, dental caries, chewing gum, , and saliva. Thematic analysis dives deep into how sugar alcohols relate to oral health, using different methods to study their effectiveness, safety, and how they affect the oral microbiome. The analysis of topic trends indicates ongoing exploration of sorbitol and xylitol, with an increasing emphasis on the potential advantages of xylitol. Additionally, there is notable attention on cariostatic agents, strategies for dental caries prevention, and the emergence of novel research domains like probiotics and erythritol, showcasing the dynamic evolution of oral health research focuses and developments. Overall, this analysis provides valuable insights into the distribution and trends of clinical trial publications, contributing to a nuanced understanding of the research landscape in sugar alcohol and oral health.
PubMed: 38872648
DOI: 10.7759/cureus.60248 -
Pest Management Science Jun 2024Development of insecticide resistance in the major malaria vectors has necessitated the development of novel vector control tools. One such strategy involves the use of...
Polyols induce acute oxidative stress and mortality in Indian malaria vector Anopheles stephensi (Diptera: Culicidae): potential for use as sugar-cum-toxin source in toxic sugar baits.
BACKGROUND
Development of insecticide resistance in the major malaria vectors has necessitated the development of novel vector control tools. One such strategy involves the use of toxic sugar baits that targets the sugar-feeding behaviour of mosquito vectors. In this study, we investigated the potential of polyols, as a toxic food (sugar) source in toxic sugar baits against the malaria vector Anopheles stephensi Liston. We examined the acute toxicity of six polyols, namely, erythritol, glycerol, mannitol, propylene glycol (PG), sorbitol, and xylitol on adult female An. stephensi mosquitoes at two different concentrations - 2% and 10%. We also studied changes in fecundity, egg hatchability and mid-gut peroxide levels induced by polyol exposure.
RESULTS
Among the six polyol compounds tested, PG was most toxic and lethal followed by glycerol and erythritol (P < 0.001) compared to the control (sucrose). PG induced acute mortality at different tested concentrations. In the erythritol- and glycerol-fed groups, a dose-dependent effect on mortality was observed. Glycerol evidently reduced fecundity and egg-hatchability in gonotrophic cycles G1 and G2. Sucrose was the preferred food source (48%), followed by erythritol (18%), PG (10%) and glycerol (8%). Ingestion of polyols increased peroxide levels in mosquito guts, which persisted for extended durations ultimately resulting in rapid mortality (P < 0.05).
CONCLUSION
The present study highlights the usefulness of sugar polyols for the development of toxic sugar baits with minimal yet effective ingredients. Further research could be focused on field experiments and on the exploration of synergistic effects of different polyols for optimization of field applications. © 2024 Society of Chemical Industry.
PubMed: 38872579
DOI: 10.1002/ps.8245 -
Current Drug Delivery Jun 2024Desloratadine, a second-generation antihistaminic drug, is poorly watersoluble and requires amelioration of the dissolution rate to improve its pharmacokinetics...
INTRODUCTION
Desloratadine, a second-generation antihistaminic drug, is poorly watersoluble and requires amelioration of the dissolution rate to improve its pharmacokinetics properties.
METHOD
This study investigated the impact of polymer, surfactant types, and concentration on the particle size, zeta potential, and dissolution efficiency of nanosuspensions formulated through the solvent antisolvent precipitation method. To optimize the delivery of Desloratadine nanosuspension, we used Minitab software and a 4-factor, 2-level full factorial design. Physicochemical properties and drug release studies were conducted to evaluate the suggested nanosuspension formulations. The optimization goals included minimizing particle size and zeta potential while maximizing dissolution efficiencies.
RESULT
The selected optimal nanosuspension demonstrated favourable values, including a particle size of 478.63 ± 15.67 nm, a zeta potential of -36.24 ± 3.21 mV, and dissolution efficiencies in double distilled water and buffer of 90.29 ± 3.75 % and 93.70 ± 3.67 %, respectively. The optimized formulation was subjected to additional analysis using X-ray powder diffraction (XPRD), scanning and transmission electron microscopy (SEM and TEM), and Fourier-transform infrared spectroscopy (FTIR).
CONCLUSION
The optimized nanosuspension formulation also underwent further studies under optimal lyophilization conditions, revealing the effectiveness of mannitol as a cryoprotectant at a concentration of 8%.
PubMed: 38867526
DOI: 10.2174/0115672018312715240604054857 -
A&A Practice Jun 2024Central neurogenic hyperventilation (CNH) is a rare disease, caused by chemical or mechanical disturbance of respiratory centers. It is characterized by the absence of...
Central neurogenic hyperventilation (CNH) is a rare disease, caused by chemical or mechanical disturbance of respiratory centers. It is characterized by the absence of extracerebral respiratory stimuli. A woman developed severe respiratory alkalosis and lactatemia after resection of a posterior fossa meningioma despite lack of cardio-respiratory or metabolic alterations. Cerebral computed tomography (cCT) revealed edema of the pontomedullary area. Treatment with mannitol and dexamethasone reestablished normal breathing patterns. Lactatemia was likely due to reduced splanchnic lactate utilization. Intracranial pathologies should be suspected in case of hyperventilation without overt reasons. cCT to confirm edema or ischemia and prompt treatment is suggested.
Topics: Humans; Female; Meningioma; Alkalosis, Respiratory; Meningeal Neoplasms; Mannitol; Middle Aged; Dexamethasone; Hyperlactatemia; Infratentorial Neoplasms; Tomography, X-Ray Computed; Postoperative Complications
PubMed: 38864528
DOI: 10.1213/XAA.0000000000001800 -
Chemical Communications (Cambridge,... Jun 2024The total synthesis of 1,4a-di--pancratistatin, a novel stereoisomer of the anti-tumor alkaloid pancratistatin, was achieved in 14 steps starting from D-mannitol. The...
The total synthesis of 1,4a-di--pancratistatin, a novel stereoisomer of the anti-tumor alkaloid pancratistatin, was achieved in 14 steps starting from D-mannitol. The construction of the pancratistatin skeleton involved conjugate addition of organocuprate to a nitrosoolefin, which was generated from inosose oxime. This was followed by stereoselective reduction of the oxime to an amine and site-selective formylation. Biological evaluations revealed that the newly synthesized compounds exhibit cytotoxicity toward cancer cells and significant ferroptosis inhibitory activity. These compounds constitute a promising small-molecule library for the development of potent bioactive agents.
Topics: Amaryllidaceae Alkaloids; Humans; Stereoisomerism; Cell Line, Tumor; Isoquinolines; Antineoplastic Agents; Drug Screening Assays, Antitumor; Molecular Structure; Cell Proliferation; Structure-Activity Relationship; Cell Survival
PubMed: 38864269
DOI: 10.1039/d4cc02199a -
Brain Injury Jun 2024This study aimed to find out the efficacy of using Hypertonic saline solution (HSS) over mannitol in the management of TBI by comparing their performance in improving... (Review)
Review
OBJECTIVE
This study aimed to find out the efficacy of using Hypertonic saline solution (HSS) over mannitol in the management of TBI by comparing their performance in improving different outcomes.
METHODS
Electronic databases were searched for randomized controlled trials (RCTs) assessing the impact of HSS vs. mannitol on ICP in patients who suffered TBI. Outcomes of interest were mortality, neurologic functional outcomes, risk ratio (RR) of successful ICP treatment, reduction in ICP after 30-60 and 90-120 min, improvement in cerebral perfusion pressure (CPP) at 30-60 and 90-120 min, and also treatment failure. Evaluations were reported as RR or mean difference (MD) with 95% confidence intervals (CIs) using weighted random-effects models.
RESULTS
The analysis included 624 patients from 15 RCTs. HSS infusion had a significant impact on the improvement of CPP at 30-60 min [MD = 5.54, 95% CI (3.04, 8.03), < 0.001] compared to mannitol. However, results yielded no significant difference between HSS and mannitol in terms of mortality, neurologic functional outcomes, successful ICP treatment, reduction in ICP after 30-60 min and 90-120 min, improvement in CPP at 90-120 min, and treatment failure.
CONCLUSION
HSS and mannitol are both effective treatments for elevated ICP due to TBI. However, further research is required to derive a better comparison.
PubMed: 38853675
DOI: 10.1080/02699052.2024.2363340 -
BMC Genomics Jun 2024KNOXs, a type of homeobox genes that encode atypical homeobox proteins, play an essential role in the regulation of growth and development, hormonal response, and...
Genome-wide identification and expression analysis of the KNOX family and its diverse roles in response to growth and abiotic tolerance in sweet potato and its two diploid relatives.
KNOXs, a type of homeobox genes that encode atypical homeobox proteins, play an essential role in the regulation of growth and development, hormonal response, and abiotic stress in plants. However, the KNOX gene family has not been explored in sweet potato. In this study, through sequence alignment, genomic structure analysis, and phylogenetic characterization, 17, 12 and 11 KNOXs in sweet potato (I. batatas, 2n = 6x = 90) and its two diploid relatives I. trifida (2n = 2x = 30) and I. triloba (2n = 2x = 30) were identified. The protein physicochemical properties, chromosome localization, phylogenetic relationships, gene structure, protein interaction network, cis-elements of promoters, tissue-specific expression and expression patterns under hormone treatment and abiotic stresses of these 40 KNOX genes were systematically studied. IbKNOX4, -5, and - 6 were highly expressed in the leaves of the high-yield varieties Longshu9 and Xushu18. IbKNOX3 and IbKNOX8 in Class I were upregulated in initial storage roots compared to fibrous roots. IbKNOXs in Class M were specifically expressed in the stem tip and hardly expressed in other tissues. Moreover, IbKNOX2 and - 6, and their homologous genes were induced by PEG/mannitol and NaCl treatments. The results showed that KNOXs were involved in regulating growth and development, hormone crosstalk and abiotic stress responses between sweet potato and its two diploid relatives. This study provides a comparison of these KNOX genes in sweet potato and its two diploid relatives and a theoretical basis for functional studies.
Topics: Ipomoea batatas; Phylogeny; Stress, Physiological; Diploidy; Gene Expression Regulation, Plant; Plant Proteins; Multigene Family; Homeodomain Proteins; Genome, Plant; Gene Expression Profiling; Promoter Regions, Genetic
PubMed: 38844832
DOI: 10.1186/s12864-024-10470-4 -
Surgical Neurology International 2024Postoperative hyponatremia is a known complication of intracranial surgery, which can present with depressed mental status. Hyponatremia resulting in focal neurologic...
BACKGROUND
Postoperative hyponatremia is a known complication of intracranial surgery, which can present with depressed mental status. Hyponatremia resulting in focal neurologic deficits is less frequently described.
CASE DESCRIPTION
We describe a patient who, after a bifrontal craniotomy for olfactory groove meningioma, developed acute hyponatremia overnight with a decline in mental status from Glasgow coma scale (GCS) score 15 to GCS 7 and a unilateral fixed dilated pupil. Head computed tomography showed expected postoperative changes without new acute or localizing findings, such as unilateral uncal herniation. The patient's mental status and pupil immediately improved with the administration of mannitol; however, there was a subsequent decline in mental status with a preserved pupil later that morning. Hypertonic saline reversed the neurologic change, and the patient was eventually discharged without a neurologic deficit. Focal neurologic deficits need not always arise following a craniotomy from a postoperative hematoma, stroke, or other finding with radiographic correlate.
CONCLUSION
Post-craniotomy hyponatremia should now be seen as a postoperative complication that can result in both a general neurologic decline in mental status, as well as with focal neurologic signs such as a fixed, dilated pupil, which can be reversed with hyperosmolar therapy and correction of the hyponatremia.
PubMed: 38840620
DOI: 10.25259/SNI_105_2024