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1.
Indian J Nephrol ; 34(3): 237-240, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114395

RESUMEN

Background: Interleukin-6 (IL-6), a biomarker of hyperinflammatory immune response, can be used to determine the severity of coronavirus disease 2019 (COVID-19) in patients with multi-organ involvement requiring critical care. The aim of our study is to understand the utility of hemodialysis, not only in terms of reducing renal burden, but also improving the outcome by tackling the COVID cytokine storm syndrome. Materials and Methods: In this prospective, observational study, 126 patients admitted to the COVID intensive care unit (ICU) wards were treated with hemodialysis for acute kidney injury (AKI). Patients' routine baseline blood parameters were evaluated. IL-6 was measured predialysis in all patients and on the day of discharge in the patients who survived. Results: Out of total 126 patients, 79 were survivors and 47 were nonsurvivors. Among nonsurvivors, majority were older (P = 0.009). Both the groups had a higher percentage of males (78.72% and 55.69% in survivors and nonsurvivors, respectively). Mean neutrophil lymphocyte ratio (NLR) and D-dimer level were significantly higher in nonsurvivors compared to survivors (P < 0.001). Mean serum urea, creatinine, and IL-6 levels were significantly greater in nonsurvivors (P < 0.001). Mean number of hemodialysis sessions received by survivors was higher. The curve between delta IL-6 and delta serum creatinine for survivors showed a significant positive association (r = 0.819, P < 0.001). Conclusion: Our study establishes IL-6 as a poor outcome predictor in COVID ICU patients with AKI. It also emphasizes the use of hemodialysis as a cost-effective lifesaving therapeutic interventional modality to not only improve the renal outcome, but also curb the cytokine storm by reducing IL-6 levels.

2.
Biomed Res Int ; 2024: 5551209, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39118805

RESUMEN

The human tongue has been long believed to be a window to provide important insights into a patient's health in medicine. The present study introduced a novel approach to predict patient age, gender, and weight inferences based on tongue images using pretrained deep convolutional neural networks (CNNs). Our results demonstrated that the deep CNN models (e.g., ResNeXt) trained on dorsal tongue images produced excellent results for age prediction with a Pearson correlation coefficient of 0.71 and a mean absolute error (MAE) of 8.5 years. We also obtained an excellent classification of gender, with a mean accuracy of 80% and an AUC (area under the receiver operating characteristic curve) of 88%. ResNeXt model also obtained a moderate level of accuracy for weight prediction, with a Pearson correlation coefficient of 0.39 and a MAE of 9.06 kg. These findings support our hypothesis that the human tongue contains crucial information about a patient. This study demonstrated the feasibility of using the pretrained deep CNNs along with a large tongue image dataset to develop computational models to predict patient medical conditions for noninvasive, convenient, and inexpensive patient health monitoring and diagnosis.


Asunto(s)
Redes Neurales de la Computación , Lengua , Humanos , Lengua/diagnóstico por imagen , Masculino , Femenino , Adulto , Peso Corporal , Persona de Mediana Edad , Adolescente , Adulto Joven , Procesamiento de Imagen Asistido por Computador/métodos , Niño , Anciano , Preescolar , Curva ROC , Lactante , Factores de Edad
3.
Chaos ; 34(7)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949532

RESUMEN

Mitigating traffic jams is a critical step for the betterment of the urban transportation system, which comprises a large number of interconnected routes to form an intricate network. To understand distinct features of vehicular traffic flow on a network, a macroscopic two-dimensional traffic network model is proposed incorporating intra-nodal and inter-nodal vehicular interaction. Utilizing the popular techniques of nonlinear dynamics, we investigate the impact of different parameters like occupancy, entry rates, and exit rates of vehicles. The existence of saddle-node, Hopf, homoclinic, Bogdanov-Takens, and cusp bifurcations have been shown using single or biparametric bifurcation diagrams. The occurrences of different multistability (bistability/tristability) phenomena, stochastic switching, and critical transitions are explored in detail. Further, we calculate the possibility of achieving each alternative state using the basin stability metric to characterize multistability. In addition, critical transitions from free flow to congestion are identified at different magnitudes of stochastic fluctuations. The applicability of critical slowing down based generic indicators, e.g., variance, lag-1 autocorrelation, skewness, kurtosis, and conditional heteroskedasticity are investigated to forewarn the critical transition from free flow to traffic congestion. It is demonstrated through the use of simulated data that not all of the measures exhibit sensitivity to rapid phase transitions in traffic flow. Our study reveals that traffic congestion emerges because of either bifurcation or stochasticity. The result provided in this study may serve as a paradigm to understand the qualitative behavior of traffic jams and to explore the tipping mechanisms occurring in transport phenomena.

4.
Diabetes Metab Syndr ; 18(7): 103088, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39079307

RESUMEN

BACKGROUND: Short term studies have reported that yoga could be beneficial in preventing diabetes. We evaluated long term effectiveness of yoga in reducing the risk of type 2 diabetes. METHODS: This open labelled randomized controlled trial was conducted across five medical centers. Adults diagnosed with prediabetes following an oral glucose tolerance test were randomly assigned to receive a structured yoga intervention consisting of 40 minutes of specific yoga asanas pranayama in addition to standard lifestyle measures or standard lifestyle measures alone. The primary outcome of incident diabetes was compared in both groups at the end of the 3-year intervention period using intention-to-treat analysis. RESULTS: A total of 974 individuals were randomized (488 to the yoga + lifestyle group-group1 and 486 to the Lifestyle alone group-group2). After 3 years of follow-up, there was a 39.2 % reduction of the relative risk of diabetes with yoga (11.5 % in group1 vs 18.9 % in group 2). Cox proportional hazard model analysis revealed a significantly higher odds ratio of 1.74 (95 % CI 1.25-2.43) of developing diabetes in the lifestyle alone group compared to those who also performed yoga. Adherence to yoga was good with 77 % of individuals performing yoga for more than 75 % of the time. CONCLUSIONS: Structured yoga intervention along with standard lifestyle measures significantly reduces risk of type 2 diabetes when compared with those given lifestyle measures alone.

5.
Nature ; 632(8023): 50-54, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39020171

RESUMEN

Giant exoplanets orbiting close to their host stars are unlikely to have formed in their present configurations1. These 'hot Jupiter' planets are instead thought to have migrated inward from beyond the ice line and several viable migration channels have been proposed, including eccentricity excitation through angular-momentum exchange with a third body followed by tidally driven orbital circularization2,3. The discovery of the extremely eccentric (e = 0.93) giant exoplanet HD 80606 b (ref. 4) provided observational evidence that hot Jupiters may have formed through this high-eccentricity tidal-migration pathway5. However, no similar hot-Jupiter progenitors have been found and simulations predict that one factor affecting the efficacy of this mechanism is exoplanet mass, as low-mass planets are more likely to be tidally disrupted during periastron passage6-8. Here we present spectroscopic and photometric observations of TIC 241249530 b, a high-mass, transiting warm Jupiter with an extreme orbital eccentricity of e = 0.94. The orbit of TIC 241249530 b is consistent with a history of eccentricity oscillations and a future tidal circularization trajectory. Our analysis of the mass and eccentricity distributions of the transiting-warm-Jupiter population further reveals a correlation between high mass and high eccentricity.

6.
Nanoscale ; 16(29): 13905-13914, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38973506

RESUMEN

Quantum interference (QI) can strongly affect electric and thermoelectric properties of molecular junctions (MJs). So far, however, a limited number of experimental studies have explored the influence of QI on thermoelectric transport in MJs. To address this open point, we synthesized derivatives of meta-OPE3 with an electron-withdrawing nitro (-NO2) substituent or an electron-donating N,N-dimethyl amine (-NMe2) substituent, attached at two different positions of the central phenylene ring, and systematically studied the electrical conductance and thermopower of the corresponding gold-molecule-gold junctions. We show that (i) the electrical conductance of MJs depends weakly on the polarity of the substituents but strongly on the substitution position and (ii) MJs with the N,N-dimethyl amine group feature a higher thermopower than MJs with the nitro group. We also present calculations based on first principles, which explain these trends and show that the transport properties are highly sensitive to microscopic details in junctions, exhibiting destructive QI features.

7.
Arch Pharm Res ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39073743

RESUMEN

Adiponectin, an adipokine, regulates metabolic processes, including glucose flux, lipid breakdown, and insulin response, by activating adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2). We have previously shown that globular adiponectin (gAd), an endogenous form of adiponectin, has osteoanabolic and anti-catabolic effects in rodent models of postmenopausal osteopenia. Moreover, we reported the identification of a 13-mer peptide (ADP-1) from the collagen domain of adiponectin, which exhibited significant adiponectin-mimetic properties. Since the clinical development of gAd is constrained by its large size, here, we investigated the osteogenic property of ADP-1. ADP-1 induced osteoblast differentiation more potently than gAd. ADP-1 elicited osteoblast differentiation through two downstream pathways that involved the participation of adiponectin receptors. Firstly, it enhanced mitochondrial biogenesis and OxPhos, leading to osteoblast differentiation. Secondly, it activated the Akt-glycogen synthase kinase 3ß-Wnt pathway, thereby increasing osteoblast differentiation. Additionally, ADP-1 suppressed the production of receptor-activator of nuclear kappa B ligand from osteoblasts, enabling it to act as a dual-action molecule (suppressing osteoclast function besides promoting osteoblast function). In osteopenic ovariectomized rats, ADP-1 increased bone mass and strength and improved trabecular integrity by stimulating bone formation and inhibiting bone resorption. Furthermore, by increasing ATP-producing intermediates within the tricarboxylic acid cycle in bones, ADP-1 likely fueled osteoblast function. Given its dual-action mechanism and high potency, ADP-1 offers a unique opportunity to address the unmet clinical need to reset the aberrant bone remodeling in osteoporosis to normalcy, potentially offering a disease-modifying impact.

8.
J Orthop Case Rep ; 14(6): 125-129, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38911003

RESUMEN

Introduction: Pan-labral tears, commonly associated with recurrent shoulder dislocations, are a well-documented pathology. However, circumferential pan-labral tears following a first-time shoulder dislocation represent a rare and scarcely reported entity in the literature. Accurate diagnosis requires a comprehensive clinical history, physical examination, and further evaluation, often involving MRI. Even with advanced imaging, the acute nature of the injury can lead to the oversight of pan-labral tears, necessitating arthroscopic assessment for definitive diagnosis. Repairing such extensive glenoid labral tears presents a challenging task, requiring skilled surgeons to utilize accessory portals and percutaneous techniques for optimal visualization and anchor placement trajectory. To the best of our knowledge, this case report represents the first documentation of a pan-labral tear associated with a 1st-time shoulder dislocation. Case Report: A 27-year-old Asian male presented with pain and limited range of motion in the left shoulder following a single episode of anterior shoulder dislocation during cricket. Initial X-rays were unremarkable, but subsequent MRI revealed an anteroinferior labral tear with intact rotator cuffs. Arthroscopic evaluation disclosed a pan-labral tear, prompting meticulous repair under general and locoregional anesthesia. The patient achieved full recovery postoperatively. Conclusion: While pan-labral tears are typically linked to recurrent dislocations, this case underscores their occurrence in a 1st-time traumatic shoulder dislocation without overt clinical signs or fractures. Arthroscopic repair demands careful intraoperative planning to achieve optimal tensioning and alignment of labral and capsular tissues. This report contributes to the limited literature on pan-labral tears associated with initial shoulder dislocations, emphasizing the importance of arthroscopic evaluation for accurate diagnosis and successful repair.

9.
R Soc Open Sci ; 11(5): 231588, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38721130

RESUMEN

In many real-world systems, the entry rate of particles into a lane is affected by the occupancy of nearby pools. For instance, in biological networks, the concentration of molecules on the side of a membrane affects the entry of particles through the membrane. To understand the behaviour of such networks, we develop a network model of ribosome flow models (RFMs) having multiple pools where each RFM captures the dynamics of particle flow in a lane and competes for the finite resources present at the nearby pool. We study a ribosome flow model network with two pools (RFMNTP) and show that the network always admits a steady state. We then analyse the behaviour of the RFMNTP with respect to modifying the transition rate through a theoretical framework. Simulations of the RFMNTP demonstrate a counterintuitive result. For example, increasing any of the transition rates in the presence of a slow site in an RFM can increase the output rate of some RFMs and decrease the output rate of the other RFMs simultaneously. This suggests that the role of local sharing of particles incorporated is non-trivial. Finally, we illustrate how these results can provide insights into studying a network with multiple pools.

10.
Mol Biol Rep ; 51(1): 687, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38796652

RESUMEN

BACKGROUND: Alternaria blotch disease in Himachal Pradesh, India, caused by Alternaria spp., adversely affects apple cultivars, resulting in reduced fruit size and quality accompanied by premature leaf fall. METHODS AND RESULTS: Sixteen Alternaria isolates from apple growing regions underwent comprehensive analysis including morphology, pathogenicity, and molecular characterization. Variations in conidiophore and conidia dimensions, shapes, and divisions were observed among isolates. Pathogenicity assays revealed differences in incubation periods, latent phases, and disease responses. Molecular characterization via nuclear ITS rDNA and RAPD analysis indicated 99-100% homology with Alternaria alternata, Alternaria mali, and other Alternaria spp., with a close phylogenetic relationship to Chinese isolates. Differentiation of isolates based on origin, cultural characteristics, and morphology was achieved using RAPD markers. CONCLUSIONS: The study identifies diverse genotypes and morphotypes of Alternaria contributing to apple blotch disease in Himachal Pradesh. These findings highlight the complexity of the pathogenic environment and hold significant implications for disease management in apple orchards.


Asunto(s)
Alternaria , Malus , Filogenia , Enfermedades de las Plantas , Alternaria/patogenicidad , Alternaria/genética , Malus/microbiología , India , Enfermedades de las Plantas/microbiología , Técnica del ADN Polimorfo Amplificado Aleatorio , ADN de Hongos/genética , Esporas Fúngicas/genética
12.
Phys Rev E ; 109(3-1): 034132, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38632803

RESUMEN

The motivation for the proposed work is drawn from the attachment-detachment observed in biological and physical transport processes that entail finite resources. We investigate the influence of limited particle availability on particle dynamics within two parallel totally asymmetric simple exclusion lanes, with one lane incorporating only particle detachment and the other considering particle attachment. We establish a theoretical framework by employing vertical mean-field theory in conjunction with singular perturbation technique. The analytical findings are supported by numerical and stochastic validation using a finite-difference scheme and the Gillespie algorithm. By utilizing these approaches, we scrutinize various stationary properties, including particle densities, phase boundaries, and particle currents for both lanes. Our analysis reveals that the complexity of the phase diagram exhibits a nonmonotonic trend in the number of stationary phases as the particle count increases. Each phase diagram is constructed with respect to the intrinsic boundary parameters, illustrating both bulk and surface transitions occurring within the lanes. The interplay between finite resources and coupling mechanisms gives rise to two phases involving upward shock in one of the lanes, while two phases exhibit synchronized downward shock in both lanes. Finally, we delve into shock dynamics to comprehend critical phase transitions occurring in the system.

13.
Indian J Otolaryngol Head Neck Surg ; 76(1): 78-83, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38440580

RESUMEN

The present study was undertaken to compare the results of various autogenous tissues: temporalis fascia, sliced tragal cartilage and fascia lata as graft materials for type I tympanoplasty in terms of hearing improvement in safe type of chronic suppurative otitis media. A total of 75 cases with central perforation were considered in the study. Of the 75 cases, temporalis fascia graft was used in 25 cases (Group-A), fascia lata graft in 25 cases (Group-B), and sliced tragal cartilage graft in 25 cases (Group-C). The results were evaluated in the form of hearing improvement with respect to the graft materials. A significant association was observed between the groups, that is, temporalis fascia (Group-A), fascia lata (Group-B), and sliced tragal cartilage (Group-C) in terms of improvement in AB gap (P = 0.047). Improvement in AB gap was statistically significant between groups B and A, but not between the other groups. In the present study, fascia lata showed better graft uptake as compared to temporalis fascia and sliced tragal cartilage. The hearing assessment at post-operative 3rd month showed statistically significant hearing improvement with fascia lata when compared to temporalis fascia.

14.
Phys Rev E ; 109(2-1): 024109, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38491687

RESUMEN

Inspired by the process of mRNA translation, in which the stochastic degradation of mRNA-ribosome machinery is modeled by the resetting dynamics, we study an open totally asymmetric simple exclusion process with local resetting at the entry site in a resource-constrained environment. The effect of constrained resources on the stationary properties of the system has been comprehended in the form of the filling factor. The mean-field approximations are utilized to obtain stationary state features, such as density profiles and phase diagrams. The phase diagram possesses pure phases as well as coexisting phases, including a low-density-high-density phase separation, which did not manifest under periodic boundary conditions despite the system being closed there as well. The role of the resetting rate has been investigated on the stationary properties of the system, depending on how the filling factor scales with the system size. In contrast to the resetting model for infinite resources, two distinct phase transitions are observed for the smaller values of the filling factor leading to a change in the topology of the phase diagram. The impact of the resetting rate along with the finite-size effect has also been examined on the shock dynamics. All the mean-field results are found in remarkable agreement with the Monte Carlo simulations.

16.
J Orthop Case Rep ; 14(2): 165-172, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38420251

RESUMEN

Introduction: It can be challenging to treat proximal humeral non-union (PHN). The challenge gets compounded when they are presented either late or after previous surgery. The challenges are far greater due to small proximal fragments, scalloping of the head, medial bone defect, osteoporosis, soft tissue contractures, and problems related to the previous implants. Material and Methods: In this retro-prospective study (2007-2020), we report on six cases of PHN which were presented to us more than 5 years after the original injury and managed using an intra-medullary autologous fibular strut graft (FSG) along with fixation with a proximal humeral locking plate and cancellous bone grafting. We quantified shoulder function based on constant score and disabilities of the arm, shoulder and hand (DASH) score. Results: The mean age of patients is found to be 54.3 years (range, 22-74 years) with females dominating our study. The mean pre-operative constant score is 26.33 which improved to 71.83 in the post-operative period. The mean DASH score is 77.98 preoperatively, which improved to 19.5 postoperatively. The paired sample t-test compared the difference in mean of the pre-operative and post-operative scores, which shows significant improvement in outcome. Conclusion: Even in very late PHN in poor-quality bone, the additional use of intramedullary strut grafts provides structural support to the fixation and further enhances the ability to withstand the load-start early motion and have a satisfactory functional outcome. Keywords: Non-union, proximal humerus non-union, proximal humerus fracture, proximal humerus internal locking system, locking plate, autogenous fibular strut graft.

17.
Inorg Chem ; 63(10): 4461-4473, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38421802

RESUMEN

Two iron complexes featuring the bidentate, nonconjugated N-heterocyclic carbene (NHC) 1,1'-methylenebis(3-methylimidazol-2-ylidene) (mbmi) ligand, where the two NHC moieties are separated by a methylene bridge, have been synthesized to exploit the combined influence of geometric and electronic effects on the ground- and excited-state properties of homoleptic FeIII-hexa-NHC [Fe(mbmi)3](PF6)3 and heteroleptic FeII-tetra-NHC [Fe(mbmi)2(bpy)](PF6)2 (bpy = 2,2'-bipyridine) complexes. They are compared to the reported FeIII-hexa-NHC [Fe(btz)3](PF6)3 and FeII-tetra-NHC [Fe(btz)2(bpy)](PF6)2 complexes containing the conjugated, bidentate mesoionic NHC ligand 3,3'-dimethyl-1,1'-bis(p-tolyl)-4,4'-bis(1,2,3-triazol-5-ylidene) (btz). The observed geometries of [Fe(mbmi)3](PF6)3 and [Fe(mbmi)2(bpy)](PF6)2 are evaluated through L-Fe-L bond angles and ligand planarity and compared to those of [Fe(btz)3](PF6)3 and [Fe(btz)2(bpy)](PF6)2. The FeII/FeIII redox couples of [Fe(mbmi)3](PF6)3 (-0.38 V) and [Fe(mbmi)2(bpy)](PF6)2 (-0.057 V, both vs Fc+/0) are less reducing than [Fe(btz)3](PF6)3 and [Fe(btz)2(bpy)](PF6)2. The two complexes show intense absorption bands in the visible region: [Fe(mbmi)3](PF6)3 at 502 nm (ligand-to-metal charge transfer, 2LMCT) and [Fe(mbmi)2(bpy)](PF6)2 at 410 and 616 nm (metal-to-ligand charge transfer, 3MLCT). Lifetimes of 57.3 ps (2LMCT) for [Fe(mbmi)3](PF6)3 and 7.6 ps (3MLCT) for [Fe(mbmi)2(bpy)](PF6)2 were probed and are somewhat shorter than those for [Fe(btz)3](PF6)3 and [Fe(btz)2(bpy)](PF6)2. [Fe(mbmi)3](PF6)3 exhibits photoluminescence at 686 nm (2LMCT) in acetonitrile at room temperature with a quantum yield of (1.2 ± 0.1) × 10-4, compared to (3 ± 0.5) × 10-4 for [Fe(btz)3](PF6)3.

18.
ACS Infect Dis ; 10(3): 845-857, 2024 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-38363869

RESUMEN

Myeloid differentiation factor 2 (MD2), the TLR4 coreceptor, has been shown to possess opsonic activity and has been implicated in phagocytosis and intracellular killing of Gram-negative bacteria. However, any MD2 protein segment involved in phagocytosis of Gram-negative bacteria is not yet known. A short synthetic MD2 segment, MD54 (amino acid regions 54 to 69), was shown to interact with a Gram-negative bacterial outer membrane component, LPS, earlier. Furthermore, the MD54 peptide induced aggregation of LPS and facilitated its internalization in THP-1 cells. Currently, it has been investigated if MD2-derived MD54 possesses any opsonic property and role in phagocytosis of Gram-negative bacteria. Remarkably, we observed that MD54 facilitated agglutination of Gram-negative bacteria, Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC BAA-427), but not of Gram-positive bacteria, Bacillus subtilis (ATCC 6633) and Staphylococcus aureus (ATCC 25923). The MD54-opsonized Gram-negative bacteria internalized within PMA-treated THP-1 cells and were killed over a longer incubation period. However, both internalization and intracellular killing of the MD54-opsonized Gram-negative bacteria within THP-1 phagocytes were appreciably inhibited in the presence of a phagocytosis inhibitor, cytochalasin D. Furthermore, MD54 facilitated the clearance of Gram-negative bacteria E. coli (ATCC 25922) and P. aeruginosa (ATCC BAA-427) from the infected BALB/c mice whereas an MD54 analog, MMD54, was inactive. Overall, for the first time, the results revealed that a short MD2-derived peptide can specifically agglutinate Gram-negative bacteria, act as an opsonin for these bacteria, and facilitate their phagocytosis by THP-1 phagocytes. The results suggest that the MD54 segment could have a crucial role in MD2-mediated host-pathogen interaction involving the Gram-negative bacteria.


Asunto(s)
Escherichia coli , Lipopolisacáridos , Animales , Ratones , Lipopolisacáridos/metabolismo , Escherichia coli/metabolismo , Fagocitosis , Macrófagos/metabolismo , Bacterias Gramnegativas/metabolismo
19.
Inorg Chem ; 63(6): 2909-2918, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38301278

RESUMEN

We here report the synthesis of the homoleptic iron(II) N-heterocyclic carbene (NHC) complex [Fe(miHpbmi)2](PF6)4 (miHpbmi = 4-((3-methyl-1H-imidazolium-1-yl)pyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)) and its electrochemical and photophysical properties. The introduction of the π-electron-withdrawing 3-methyl-1H-imidazol-3-ium-1-yl group into the NHC ligand framework resulted in stabilization of the metal-to-ligand charge transfer (MLCT) state and destabilization of the metal-centered (MC) states. This resulted in an improved excited-state lifetime of 16 ps compared to the 9 ps for the unsubstituted parent compound [Fe(pbmi)2](PF6)2 (pbmi = (pyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)) as well as a stronger MLCT absorption band extending more toward the red spectral region. However, compared to the carboxylic acid derivative [Fe(cpbmi)2](PF6)2 (cpbmi = 1,1'-(4-carboxypyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)), the excited-state lifetime of [Fe(miHpbmi)2](PF6)4 is the same, but both the extinction and the red shift are more pronounced for the former. Hence, this makes [Fe(miHpbmi)2](PF6)4 a promising pH-insensitive analogue of [Fe(cpbmi)2](PF6)2. Finally, the excited-state dynamics of the title compound [Fe(miHpbmi)2](PF6)4 was investigated in solvents with different viscosities, however, showing very little dependency of the depopulation of the excited states on the properties of the solvent used.

20.
Biochem J ; 481(4): 191-218, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38224573

RESUMEN

Insulin resistance (IR) is the key pathophysiological cause of type 2 diabetes, and inflammation has been implicated in it. The death domain (DD) of the adaptor protein, MyD88 plays a crucial role in the transduction of TLR4-associated inflammatory signal. Herein, we have identified a 10-residue peptide (M10), from the DD of MyD88 which seems to be involved in Myddosome formation. We hypothesized that M10 could inhibit MyD88-dependent TLR4-signaling and might have effects on inflammation-associated IR. Intriguingly, 10-mer M10 showed oligomeric nature and reversible self-assembly property indicating the peptide's ability to recognize its own amino acid sequence. M10 inhibited LPS-induced nuclear translocation of NF-κB in L6 myotubes and also reduced LPS-induced IL-6 and TNF-α production in peritoneal macrophages of BALB/c mice. Remarkably, M10 inhibited IL-6 and TNF-α secretion in diabetic, db/db mice. Notably, M10 abrogated IR in insulin-resistant L6 myotubes, which was associated with an increase in glucose uptake and a decrease in Ser307-phosphorylation of IRS1, TNF-α-induced JNK activation and nuclear translocation of NF-κB in these cells. Alternate day dosing with M10 (10 and 20 mg/kg) for 30 days in db/db mice significantly lowered blood glucose and improved glucose intolerance after loading, 3.0 g/kg glucose orally. Furthermore, M10 increased insulin and adiponectin secretion in db/db mice. M10-induced glucose uptake in L6 myotubes involved the activation of PI3K/AKT/GLUT4 pathways. A scrambled M10-analog was mostly inactive. Overall, the results show the identification of a 10-mer peptide from the DD of MyD88 with anti-inflammatory and anti-diabetic properties, suggesting that targeting of TLR4-inflammatory pathway, could lead to the discovery of molecules against IR and diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Animales , Ratones , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Glucemia , Dominio de Muerte , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Inflamación/tratamiento farmacológico , Insulina/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolisacáridos/toxicidad , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Péptidos/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
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