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1.
bioRxiv ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39257780

RESUMEN

Mass-drug administration (MDA) of human populations using praziquantel monotherapy has become the primary strategy for controlling and potentially eliminating the major neglected tropical disease schistosomiasis. To understand how long-term MDA impacts schistosome populations, we analysed whole-genome sequence data of 570 Schistosoma mansoni samples (and the closely related outgroup species, S. rodhaini) from eight countries incorporating both publicly-available sequence data and new parasite material. This revealed broad-scale genetic structure across countries but with extensive transmission over hundreds of kilometres. We characterised variation across the transient receptor potential melastatin ion channel, TRPMPZQ, a target of praziquantel, which has recently been found to influence praziquantel susceptibility. Functional profiling of TRPMPZQ variants found in endemic populations identified four mutations that reduced channel sensitivity to praziquantel, indicating standing variation for resistance. Analysis of parasite infrapopulations sampled from individuals pre- and post-treatment identified instances of treatment failure, further indicative of potential praziquantel resistance. As schistosomiasis is targeted for elimination as a public health problem by 2030 in all currently endemic countries, and even interruption of transmission in selected African regions, we provide an in-depth genomic characterisation of endemic populations and an approach to identify emerging praziquantel resistance alleles.

2.
Acta Neurochir (Wien) ; 166(1): 370, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39283335

RESUMEN

BACKGROUND: Intraprocedural rupture (IPR) is a devastating complication of cerebral aneurysm treatment. While several studies have investigated its risk factors and clinical impact, further research with larger populations is warranted. METHODS: We retrospectively reviewed data from 4,039 patients with 4,233 cerebral aneurysms treated at our institution between January 2009 and December 2018. Multivariate logistic regression with stepwise elimination was performed to identify the independent risk factors of IPR. Unfavorable clinical outcome was defined as a Modified Rankin Scale (mRS) ≥ 3 points at 3 months post-treatment. RESULTS: IPR occurred in 61 (1.44%) of the 4,233 aneurysms. Multivariate analysis showed that previously ruptured aneurysms (odds ratio [OR] 3.182; 95% confidence interval [CI] 1.851-5.470; p < 0.001), surgical clipping (OR 3.598; 95% CI 1.894-6.836; p < 0.001), and higher aspect ratio (OR 1.310; 95% CI 1.032-1.663; p = 0.024) were independent risk factors for IPR. Patients with IPR had significantly higher rates of unfavorable clinical outcomes (mRS ≥ 3) compared to those without (18.0% vs. 3.3%, p < 0.001). However, within the ruptured aneurysm subgroup, the rate of unfavorable outcomes did not differ significantly between IPR and non-IPR groups (22.7% vs. 19.2%, p = 0.594). CONCLUSION: Ruptured aneurysms, surgical clipping, and higher aspect ratio were independently associated with IPR. IPR significantly increased the risk of unfavorable clinical outcomes regardless of treatment approach, except in the subgroup of ruptured aneurysms.


Asunto(s)
Aneurisma Roto , Aneurisma Intracraneal , Humanos , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/complicaciones , Aneurisma Roto/cirugía , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Factores de Riesgo , Resultado del Tratamiento , Adulto , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Procedimientos Neuroquirúrgicos/métodos
3.
Angew Chem Int Ed Engl ; : e202415821, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39252675

RESUMEN

Molecular crystals capable of colossal thermal expansion (TE) are fascinating owing to their substantial and continuous volume changes and reasonably linear responses to temperature. This makes them promising candidates for micromachine applications. Macroscopic motion is driven by subtle yet cooperative movements of molecules that respond to the thermal motions of dynamic functional units. The study of p-TIPS-DSB presented here offers a compelling case highlighting the relationship between the degree of dynamicity of functional units and TE behavior. In its α-phase, the p-TIPS-DSB crystal undergoes an irreversible martensitic transition to the ß-phase, accompanied by significant cooperative interlayer shear. This process substantially enhances the mobility of the side-chains driven by the increased free volume surrounding them. This nearly doubles the volumetric TE coefficient from 255.3 (10) to 444.9 (32) MK-1, particularly in the actuation direction from 175.0 (7) to 291.7 (20) MK-1, enabling about 4.5% elongation/contraction. As demonstrated here, p-TIPS-DSB exhibits a decent force density (> 1.4 × 107 N m-3) and precise motion control capabilities due to its hysteresis-free and non-abrupt TE nature. Furthermore, we demonstrated the limited operating distance of colossal TE materials can be amplified by utilizing levers, highlighting the high potential of these materials for use in micromachines.

4.
Blood Res ; 59(1): 29, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39196490

RESUMEN

PURPOSE: This study aimed to investigate the pharmacokinetics (PK) of factor VIII (FVIII) in Korean patients, as limited information is available on the PK of FVIII in this population. METHODS: We collected the FVIII PK results from patients with moderate-to-severe hemophilia A using myPKFiT. PK variations were assessed according to age, blood type, inhibitor history, von Willebrand factor antigen (vWF:Ag) level, and body mass index. Additionally, the correlation between the PK profile and prophylaxis regimen was specifically analyzed for each product in severe cases. RESULTS: The PK data of 48 and 81 patients treated with octocog alfa and rurioctocog alfa pegol, respectively, were obtained. The median half-lives of octocog alfa and rurioctocog alfa pegol were 9.9 (range: 6.3-15.2) h and 15.3 (range: 10.4-23.9) h, respectively. The PK profiles for each product did not differ according to age group; however, blood type-O patients had shorter half-lives and time to 1% compared to non-blood type-O patients. In regression analysis, the PK of octocog alfa showed a statistically significant difference according to age, whereas the PK of rurioctocog alfa pegol correlated with vWF:Ag. Only the frequency of rurioctocog alfa pegol use showed a statistically significant difference in relation to time to 1%, although the coefficient of determination was small. CONCLUSION: This study confirmed significant interpatient variation in the PK of FVIII among Korean patients with hemophilia A. To achieve optimized prophylaxis, personalizing the regimen based on the PK profile of each individual patient is essential.

5.
World Neurosurg ; 189: e1013-e1021, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39004183

RESUMEN

BACKGROUND: This retrospective study aimed to compare the efficacy of balloon angioplasty alone (BAA) with carotid artery stenting (CAS) for severe extracranial carotid artery stenosis. The primary outcomes assessed were restenosis requiring retreatment and symptomatic stroke occurrence within a 4-year follow-up period. METHODS: A total of 77 patients with 89 carotid artery stenoses undergoing endovascular carotid revascularization between January 2015 and December 2019 were included. Neuroradiologic evaluations, including computed tomography angiography or magnetic resonance angiography, were performed at defined intervals. Statistical analyses were conducted to compare patient characteristics, angiographic outcomes, and clinical outcomes between the BAA and CAS groups. RESULTS: The study demonstrated successful outcomes in both groups with low adverse event rates. The overall restenosis rate was 40.2%, but severe restenosis requiring retreatment occurred in only 10 cases (7 in BAA, and 3 in CAS). No significant difference was found in retreatment rates between the 2 groups (P = 0.53). Stroke occurrence within the 4-year follow-up period was observed in 3 patients, with no statistically significant difference between BAA and CAS groups. CONCLUSIONS: This study provides valuable insights into the comparative effectiveness of BAA and CAS for severe extracranial carotid artery stenosis. Despite slightly shorter intervals to restenosis in the BAA group, there was no significant difference in retreatment or stroke occurrence rates between the 2 procedures. BAA offers advantages in terms of retreatment options.


Asunto(s)
Angioplastia de Balón , Estenosis Carotídea , Stents , Humanos , Estenosis Carotídea/cirugía , Estenosis Carotídea/diagnóstico por imagen , Masculino , Estudios Retrospectivos , Femenino , Anciano , Angioplastia de Balón/métodos , Persona de Mediana Edad , Resultado del Tratamiento , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/cirugía , Anciano de 80 o más Años
6.
Am J Physiol Cell Physiol ; 327(1): C151-C167, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38798270

RESUMEN

Substance P (SP) is released from sensory nerves in the arteries and heart. It activates neurokinin-1 receptors (NK1Rs) causing vasodilation, immune modulation, and adverse cardiac remodeling. The hypothesis was tested: SP and SP metabolites activate different second messenger signaling pathways. Macrophages, endothelial cells, and fibroblasts metabolized SP to N- and C-terminal metabolites to varying extents. SP 5-11 was the most abundant metabolite followed by SP 1-4, SP 7-11, SP 6-11, SP 3-11, and SP 8-11. In NK1R-expressing human embryonic kidney 293 (HEK293) cells, SP and some C-terminal SP metabolites stimulate the NK1R, promoting the dissociation of several Gα proteins, including Gαs and Gαq from their ßγ subunits. SP increases intracellular calcium concentrations ([Ca]i) and cyclic 3',5'-adenosine monophosphate (cAMP) accumulation with similar -log EC50 values of 8.5 ± 0.3 and 7.8 ± 0.1 M, respectively. N-terminal metabolism of SP by up to five amino acids and C-terminal deamidation of SP produce peptides that retain activity to increase [Ca]i but not to increase cAMP. C-terminal metabolism results in the loss of both activities. Thus, [Ca]i and cAMP signaling are differentially affected by SP metabolism. To assess the role of N-terminal metabolism, SP and SP 6-11 were compared with cAMP-mediated activities in NK1R-expressing 3T3 fibroblasts. SP inhibits nuclear factor κB (NF-κB) activity, cell proliferation, and wound healing and stimulates collagen production. SP 6-11 had little or no activity. Cyclooxygenase-2 (COX-2) expression is increased by SP but not by SP 6-11. Thus, metabolism may select the cellular response to SP by inhibiting or redirecting the second messenger signaling pathway activated by the NK1R.NEW & NOTEWORTHY Endothelial cells, macrophages, and fibroblasts metabolize substance P (SP) to N- and C-terminal metabolites with SP 5-11 as the most abundant metabolite. SP activates neurokinin-1 receptors to increase intracellular calcium and cyclic AMP. In contrast, SP metabolites of N-terminal metabolism and C-terminal deamidation retain the ability to increase calcium but lose the ability to increase cyclic AMP. These new insights indicate that the metabolism of SP directs cellular functions by regulating specific signaling pathways.


Asunto(s)
AMP Cíclico , Receptores de Neuroquinina-1 , Transducción de Señal , Sustancia P , Sustancia P/metabolismo , Receptores de Neuroquinina-1/metabolismo , Receptores de Neuroquinina-1/agonistas , Humanos , AMP Cíclico/metabolismo , Animales , Células HEK293 , Ratones , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Calcio/metabolismo
7.
Nat Struct Mol Biol ; 31(9): 1386-1393, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38714890

RESUMEN

Diseases caused by parasitic flatworms impart a considerable healthcare burden worldwide. Many of these diseases-for example, the parasitic blood fluke infection schistosomiasis-are treated with the drug praziquantel (PZQ). However, PZQ is ineffective against disease caused by liver flukes from the genus Fasciola because of a single amino acid change within the target of PZQ, a transient receptor potential ion channel in the melastatin family (TRPMPZQ), in Fasciola species. Here, we identify benzamidoquinazolinone analogs that are active against Fasciola TRPMPZQ. Structure-activity studies define an optimized ligand (BZQ) that caused protracted paralysis and tegumental damage to these liver flukes. BZQ also retained activity against Schistosoma mansoni comparable to PZQ and was active against TRPMPZQ orthologs in all profiled species of parasitic fluke. This broad-spectrum activity manifests as BZQ adopts a pose within the binding pocket of TRPMPZQ that is dependent on a ubiquitously conserved residue. BZQ therefore acts as a universal activator of trematode TRPMPZQ and a first-in-class, broad-spectrum flukicide.


Asunto(s)
Schistosoma mansoni , Animales , Schistosoma mansoni/efectos de los fármacos , Antihelmínticos/farmacología , Antihelmínticos/química , Relación Estructura-Actividad , Descubrimiento de Drogas , Ratones , Modelos Moleculares , Proteínas del Helminto/metabolismo , Proteínas del Helminto/química , Proteínas del Helminto/genética , Praziquantel/farmacología , Praziquantel/química
8.
Chemistry ; 30(45): e202401023, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-38807442

RESUMEN

Flexible optoelectronics is the need of the hour as the market moves toward wearable and conformable devices. Crystalline π-conjugated materials offer high performance as active materials compared to their amorphous counterpart, but they are typically brittle. This poses a significant challenge that needs to be overcome to unfold their potential in optoelectronic devices. Unveiling the molecular packing topology and identifying interaction descriptors that can accommodate strain offers essential guiding principles for developing conjugated materials as active components in flexible optoelectronics. The molecular packing and interaction topology of eight crystal systems of dicyano-distyrylbenzene derivatives are investigated. Face-to-face π-stacks in an inclined orientation relative to the bending surface can accommodate expansion and compression with minimal molecular motion from their equilibrium positions. This configuration exhibits good compliance towards mechanical strain, while a similar structure with a criss-cross arrangement capable of distributing applied strain equally in opposite directions enhances the flexibility. Molecular arrangements that cannot reversibly undergo expansion and compression exhibit brittleness. In the isometric CT crystals, the disproportionate strength of the interactions along the bending plane and orthogonal directions makes these materials sustain a moderate bending strain. These results provide an updated explanation for the elastic bending in semiconducting π-conjugated crystals.

10.
Antioxidants (Basel) ; 13(2)2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38397753

RESUMEN

Butein is a flavonoid found in many plants, including dahlia, butea, and coreopsis, and has both antioxidant and sirtuin-activating activities. In light of the postulated role of free radicals in aging, we examined the effects of butein on aging and on genetic or nutritional models of age-related diseases in Caenorhabditis elegans. Butein showed radical scavenging activity and increased resistance to oxidative stress in Caenorhabditis elegans. The mean lifespan of Caenorhabditis elegans was significantly increased by butein, from 22.7 days in the untreated control to 25.0 days in the butein-treated group. However, the lifespan-extending effect of butein was accompanied by reduced production of progeny as a trade-off. Moreover, the age-related decline in motility was delayed by butein supplementation. Genetic analysis showed that the lifespan-extending effect of butein required the autophagic protein BEC-1 and the transcription factor DAF-16 to regulate stress response and aging. At the genetic level, expression of the DAF-16 downstream target genes hsp-16.2 and sod-3 was induced in butein-treated worms. Butein additionally exhibited a preventive effect in models of age-related diseases. In an Alzheimer's disease model, butein treatment significantly delayed the paralysis caused by accumulation of amyloid-beta in muscle, which requires SKN-1, not DAF-16. In a high-glucose-diet model of diabetes mellitus, butein markedly improved survival, requiring both SKN-1 and DAF-16. In a Parkinson's disease model, dopaminergic neurodegeneration was completely inhibited by butein supplementation and the accumulation of α-synuclein was significantly reduced. These findings suggest the use of butein as a novel nutraceutical compound for aging and age-related diseases.

11.
Neurosurgery ; 94(3): 597-605, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37800926

RESUMEN

BACKGROUND AND OBJECTIVE: Perioperative low-dose aspirin (ASA) management for open craniotomy surgery lacked information. We analyze to establish the perioperative ASA strategy to minimize both hemorrhagic and thromboembolic complications. METHODS: The investigators designed a multicenter retrospective study, which included patients scheduled to have clipping surgery for unruptured intracranial aneurysm. The incidence and risk factors were analyzed for postoperative hemorrhagic complications and major cardio- and cerebrovascular events (MACCEs) within 1 month postoperation. RESULTS: This study included 503 long-term ASA users of 3654 patients at three tertiary centers. The incidence of hemorrhagic complications and MACCEs was 7.4% (37/503) and 8.8% (44/503), respectively. Older age (>70 years, odds ratio [OR]: 2.928, 95% CI [1.337-6.416]), multiple aneurysms operation (OR: 2.201, 95% CI [1.017-4.765]), large aneurysm (>10 mm, OR: 4.483, 95% CI [1.485-13.533]), and ASA continuation (OR: 2.604, 95% CI [1.222-5.545]) were independent risk factors for postoperative hemorrhagic complications. Intracranial hemorrhage was the only type of hemorrhagic complication that increased in the ASA continuation group (10.6% vs 2.9%, P = .001). Between the ASA continuation and discontinuation groups, the overall incidence of MACCEs was not significantly different (log-rank P = .8). In the subgroup analysis, ASA discontinuation significantly increased the risk of MACCEs in the secondary prevention group (adjusted hazard ratio: 2.580, 95% CI [1.015-6.580]). CONCLUSION: ASA continuation increased the risk of postoperative intracranial hemorrhage. Simultaneously, ASA discontinuation was the major risk factor for postoperative MACCEs in the high-risk group. Without evidence of intracranial hemorrhage, early ASA resumption was indicated (a total cessation duration <7-10 days) in the secondary prevention group.


Asunto(s)
Aspirina , Aneurisma Intracraneal , Humanos , Estudios Retrospectivos , Aspirina/efectos adversos , Hemorragia Posoperatoria/inducido químicamente , Hemorragia Posoperatoria/epidemiología , Hemorragia Posoperatoria/prevención & control , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/tratamiento farmacológico , Factores de Riesgo , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/epidemiología , Inhibidores de Agregación Plaquetaria/efectos adversos
12.
J Biol Chem ; 300(1): 105528, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38043794

RESUMEN

Parasitic flatworms cause various clinical and veterinary infections that impart a huge burden worldwide. The most clinically impactful infection is schistosomiasis, a neglected tropical disease caused by parasitic blood flukes. Schistosomiasis is treated with praziquantel (PZQ), an old drug introduced over 40 years ago. New drugs are urgently needed, as while PZQ is broadly effective it suffers from several limitations including poor efficacy against juvenile worms, which may prevent it from being completely curative. An old compound that retains efficacy against juvenile worms is the benzodiazepine meclonazepam (MCLZ). However, host side effects caused by benzodiazepines preclude development of MCLZ as a drug and MCLZ lacks an identified parasite target to catalyze rational drug design for engineering out human host activity. Here, we identify a transient receptor potential ion channel of the melastatin subfamily, named TRPMMCLZ, as a parasite target of MCLZ. MCLZ potently activates Schistosoma mansoni TRPMMCLZ through engagement of a binding pocket within the voltage-sensor-like domain of the ion channel to cause worm paralysis, tissue depolarization, and surface damage. TRPMMCLZ reproduces all known features of MCLZ action on schistosomes, including a lower activity versus Schistosoma japonicum, which is explained by a polymorphism within this voltage-sensor-like domain-binding pocket. TRPMMCLZ is distinct from the TRP channel targeted by PZQ (TRPMPZQ), with both anthelmintic chemotypes targeting unique parasite TRPM paralogs. This advances TRPMMCLZ as a novel druggable target that could circumvent any target-based resistance emerging in response to current mass drug administration campaigns centered on PZQ.


Asunto(s)
Antihelmínticos , Clonazepam , Esquistosomiasis mansoni , Canales Catiónicos TRPM , Animales , Humanos , Antihelmínticos/farmacología , Benzodiazepinas/farmacología , Benzodiazepinonas/farmacología , Clonazepam/análogos & derivados , Clonazepam/farmacología , Praziquantel/farmacología , Schistosoma mansoni/efectos de los fármacos , Schistosoma mansoni/metabolismo , Esquistosomiasis mansoni/tratamiento farmacológico , Canales Catiónicos TRPM/agonistas
13.
ACS Med Chem Lett ; 14(11): 1537-1543, 2023 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-37970586

RESUMEN

The anthelmintic drug praziquantel remains a key clinical therapy for treating various diseases caused by parasitic flatworms. The parasite target of praziquantel has remained undefined despite longstanding usage in the clinic, although a candidate ion channel target, named TRPMPZQ, has recently been identified. Intriguingly, certain praziquantel derivatives show different activities against different parasites: for example, some praziquantel analogs are considerably more active against cestodes than against schistosomes. Here we interrogate whether the different activities of praziquantel analogs against different parasites are also reflected by unique structure-activity relationships at the TRPMPZQ channels found in these different organisms. To do this, several praziquantel analogs were synthesized and functionally profiled against schistosome and cestode TRPMPZQ channels. Data demonstrate that structure-activity relationships are closely mirrored between parasites and their TRPMPZQ orthologs, providing further support for TRPMPZQ as the therapeutically relevant target of praziquantel.

14.
bioRxiv ; 2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37790347

RESUMEN

Diseases caused by parasitic flatworms impart a considerable healthcare burden worldwide. Many of these diseases - for example, the parasitic blood fluke infection, schistosomiasis - are treated with the drug praziquantel (PZQ). However, PZQ is ineffective against disease caused by liver flukes from the genus Fasciola. This is due to a single amino acid change within the target of PZQ, a transient receptor potential ion channel (TRPMPZQ), in Fasciola species. Here we identify benzamidoquinazolinone analogs that are active against Fasciola TRPMPZQ. Structure-activity studies define an optimized ligand (BZQ) that caused protracted paralysis and damage to the protective tegument of these liver flukes. BZQ also retained activity against Schistosoma mansoni comparable to PZQ and was active against TRPMPZQ orthologs in all profiled species of parasitic fluke. This broad spectrum activity was manifest as BZQ adopts a pose within the binding pocket of TRPMPZQ dependent on a ubiquitously conserved residue. BZQ therefore acts as a universal activator of trematode TRPMPZQ and a first-in-class, broad spectrum flukicide.

15.
Artículo en Inglés | MEDLINE | ID: mdl-37813697

RESUMEN

Hyperplastic anterior choroidal artery (AchA) is an extremely rare congenital vascular variant that can be mistaken for other cerebral arteries. This case report presents a 38-year-old man who presented with a severe sudden-onset headache and was diagnosed with a ruptured aneurysm originating from a hyperplastic AchA. The aneurysm was successfully treated with coil embolization, but recurrence was detected after eight months, leading to additional surgical intervention. The discussion highlights the classification of hyperplastic AchA and emphasizes the importance of recognizing this anatomical variant to avoid complications during treatment. This case report underscores the need for awareness and understanding of hyperplastic AchA in the management of cerebral aneurysms.

16.
Microorganisms ; 11(9)2023 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-37764128

RESUMEN

Nitric oxide (NO) is a free radical associated with physiological functions such as blood pressure regulation, cardiovascular health, mitochondrial production, calcium transport, oxidative stress, and skeletal muscle repair. This study aimed to isolate Latilactobacillus curvatus strains with enhanced NO production from the traditional Korean fermented food, jangajji, and evaluate their probiotic properties for industrial purposes. When cells were co-cultured with various bacterial stimulants, NO production generally increased, and NO synthesis was observed in the range of 20-40 mg/mL. The selected strains of Lat. curvatus were resistant to acid and bile conditions and with variable effectiveness (1-14%) in adhering to Caco-2 cells. Most bacterial strains can inhibit the growth of various pathogens. In addition, they are capable of reducing cholesterol levels via assimilation of cholesterol at 10-50%. Among the selected NO synthases from Lat. curvatus strains, the strain JBCC38 showed the highest capacity to scavenge ABTS (30.1%) and DPPH radicals (39.4%). Moreover, these strains exhibited immunomodulatory properties. The production of TNF-α and IL-6 in the macrophages treated with various bacterial stimulants was induced in all the selected strains.

17.
Microorganisms ; 11(8)2023 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-37630480

RESUMEN

To understand the biological roles of Pediococcus pentosaceus strains as probiotics isolated from the traditional Korean fermented food, Jangajji, Pediococcus pentosaceus was selected based on its high cinnamoyl esterase (CE) and antioxidant activities. The acid and bile stability, intestinal adhesion, antagonistic activity against human pathogens, cholesterol-lowering effects, and immune system stimulation without inflammatory effects were evaluated. Nitric oxide (NO) levels were measured in co-culture with various bacterial stimulants. Fermentation ability was measured by using a broccoli matrix and the sulforaphane levels were measured. Resistance to acidic and bilious conditions and 8% adherence to Caco-2 cells were observed. Cholesterol levels were lowered by 51% by assimilation. Moreover, these strains exhibited immunomodulatory properties with induction of macrophage TNF-α and IL-6 and had microstatic effects on various pathogens. Co-culture with various bacterial stimulants resulted in increased NO production. Fermentation activity was increased with the strains, and higher sulforaphane levels were observed. Therefore, in the future, the applicability of the selected strain to broccoli matrix-based fermented functional foods should be confirmed.

18.
PLoS One ; 18(8): e0289493, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37531332

RESUMEN

Additive manufacturing, or 3D printing, has revolutionized the way we create objects. However, its layer-by-layer process may lead to an increased incidence of local defects compared to traditional casting-based methods. Factors such as light intensity, depth of light penetration, component inhomogeneity, and fluctuations in nozzle temperature all contribute to defect formations. These defective regions can become sources of toxic component leakage, but pinpointing their locations in 3D printed materials remains a challenge. Traditional toxicological assessments rely on the extraction and subsequent exposure of living organisms to these harmful agents, thus only offering a passive detection approach. Therefore, the development of an active system to both identify and locate sources of toxicity is essential in the realm of 3D printing technologies. Herein, we introduce the use of the nematode model organism, Caenorhabditis elegans (C. elegans), for toxicity evaluation. C. elegans exhibits distinctive 'sensing' and 'locomotion' capabilities that enable it to actively navigate toward safe zones while steering clear of hazardous areas. This active behavior sets C. elegans apart from other aquatic and animal models, making it an exceptional choice for immediate and precise identification and localization of toxicity sources in 3D printed materials.


Asunto(s)
Caenorhabditis elegans , Nematodos , Animales , Locomoción , Modelos Animales
19.
ChemMedChem ; 18(18): e202300140, 2023 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-37272317

RESUMEN

Praziquantel (PZQ) is an essential anthelmintic drug recently established to be an activator of a Transient Receptor Potential Melastatin (TRPMPZQ ) ion channel in trematode worms. Bioinformatic, mutagenesis and drug metabolism work indicate that the cyclohexyl ring of PZQ is a key pharmacophore for activation of trematode TRPMPZQ , as well as serving as the primary site of oxidative metabolism which results in PZQ being a short-lived drug. Based on our recent findings, the hydrophobic cleft in schistosome TRPMPZQ defined by three hydrophobic residues surrounding the cyclohexyl ring has little tolerance for polarity. Here we evaluate the in vitro and in vivo activities of PZQ analogues with improved metabolic stability relative to the challenge of maintaining activity on the channel. Finally, an estimation of the respective contribution to the overall activity of both the parent and the main metabolite of PZQ in humans is reported.


Asunto(s)
Antihelmínticos , Parásitos , Canales Catiónicos TRPM , Canales de Potencial de Receptor Transitorio , Humanos , Animales , Praziquantel/farmacología , Praziquantel/química , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Schistosoma mansoni
20.
Nanotechnology ; 34(32)2023 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-37146599

RESUMEN

Ambipolar field-effect transistors (FETs) possessing both electron and hole carriers enable implementation of novel reconfigurable transistors, artificial synaptic transistors, and output polarity controllable (OPC) amplifiers. Here, we fabricated a two-dimensional (2D) material-based complementary ambipolar FET and investigated its electrical characteristics. Properties of ohmic-like contacts at source/drain sides were verified from output characteristics and temperature-dependent measurements. The symmetry of electron and hole currents can be easily achieved by optimization of the MoS2or WSe2channels, different from the conventional ambipolar FET with fundamental issues related to Schottky barriers. In addition, we demonstrated successful operation of a complementary inverter and OPC amplifier, using the fabricated complementary ambipolar FET based on 2D materials.

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