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1.
World J Clin Cases ; 12(22): 4897-4904, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39109021

RESUMO

BACKGROUND: It has been confirmed that the increased posterior tibial slope over 12 degrees is a risk factor for anterior cruciate ligament injury, and varus deformity can aggravate the progression of medial osteoarthritis. AIM: To evaluate the efficacy of modified high tibial osteotomy (HTO) and anterior cruciate ligament reconstruction (ACLR) in the treatment of anterior cruciate ligament (ACL) injuries with varus deformities and increased posterior tibial slope (PTS) based on clinical and imaging data. METHODS: The patient data in this retrospective study were collected from 2019 to 2021. A total of 6 patients were diagnosed with ACL injury combined with varus deformities and increased PTS. All patients underwent modified open wedge HTO and ACLR. The degree of correction of varus deformity and the PTS was evaluated by radiography and magnetic resonance imaging. RESULTS: All 6 patients (6 knee joints) were followed up for an average of 20.8 ± 3.7 months. The average age at surgery was 29.5 ± 3.8 years. At the last follow-up, all patients resumed competitive sports. The International Knee Documentation Committee score increased from 50.3 ± 3.1 to 87.0 ± 2.8, the Lysholm score increased from 43.8 ± 4.9 to 86 ± 3.1, and the Tegner activity level increased from 2.2 ± 0.7 to 7.0 ± 0.6. The average movement distance of the tibia anterior translation was 4.8 ± 1.1 mm, medial proximal tibial angle (MPTA) was 88.9 ± 1.3° at the last follow-up, and the PTS was 8.4 ± 1.4°, both of which were significantly higher than those before surgery (P < 0.05). CONCLUSION: Modified open wedge HTO combined with ACLR can effectively treat patients with ACL ruptures with an associated increased PTS and varus deformity. The short-term effect is significant, but the long-term effect requires further follow-up.

2.
bioRxiv ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39185180

RESUMO

Background: The outer mitochondrial Rho GTPase 1, MIRO1, mediates mitochondrial motility within cells, but implications for vascular smooth muscle cell (VSMC) physiology and its roles invascular diseases, such as neointima formation following vascular injury are widely unknown. Methods: An in vivo model of selective Miro1 deletion in VSMCs was generated, and the animals were subjected to carotid artery ligation. The molecular mechanisms relevant to VSMC proliferation were then explored in explanted VSMCs by imaging mitochondrial positioning and cristae structure and assessing the effects on ATP production, metabolic function and interactions with components of the electron transport chain (ETC). Results: MIRO1 was robustly expressed in VSMCs within human atherosclerotic plaques and promoted VSMC proliferation and neointima formation in mice by blocking cell-cycle progression at G1/S, mitochondrial positioning, and PDGF-induced ATP production and respiration; overexpression of a MIRO1 mutant lacking the EF hands that are required for mitochondrial mobility did not fully rescue these effects. At the ultrastructural level, Miro1 deletion distorted the mitochondrial cristae and reduced the formation of super complexes and the activity of ETC complex I. Conclusions: Mitochondrial motility is essential for VSMC proliferation and relies on MIRO1. The EF-hands of MIRO1 regulate the intracellular positioning of mitochondria. Additionally, the absence of MIRO1 leads to distorted mitochondrial cristae and reduced ATP generation. Our findings demonstrate that motility is linked to mitochondrial ATP production. We elucidated two unrecognized mechanisms through which MIRO1 influences cell proliferation by modulating mitochondria: first, by managing mitochondrial placement via Ca2+-dependent EF hands, and second, by affecting cristae structure and ATP synthesis.

3.
World J Gastrointest Oncol ; 16(6): 2350-2361, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38994143

RESUMO

The prevention and early diagnosis of liver cancer remains a global medical challenge. During the malignant transformation of hepatocytes, a variety of oncogenic cellular signalling molecules, such as novel high mobility group-Box 3, angiopoietin-2, Golgi protein 73, glypican-3, Wnt3a (a signalling molecule in the Wnt/ß-catenin pathway), and secretory clusterin, can be expressed and secreted into the blood. These signalling molecules are derived from different signalling pathways and may not only participate in the malignant transformation of hepatocytes but also become early diagnostic indicators of hepatocarcinogenesis or specific targeted molecules for hepatocellular carcinoma therapy. This article reviews recent progress in the study of several signalling molecules as sensitive biomarkers for monitoring hepatocarcinogenesis.

4.
Am J Physiol Regul Integr Comp Physiol ; 327(1): R54-R65, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38738295

RESUMO

Obesity is a major public health issue due to its association with type 2 diabetes, hypertension, and other cardiovascular risks. The BBSome, a complex of eight conserved Bardet-Biedl syndrome (BBS) proteins, has emerged as a key regulator of energy and glucose homeostasis as well as cardiovascular function. However, the importance of adipocyte BBSome in controlling these physiological processes is not clear. Here, we show that adipocyte-specific constitutive disruption of the BBSome through selective deletion of the Bbs1 gene adiponectin (AdipoCre/Bbs1fl/fl mice) does not affect body weight under normal chow or high-fat and high-sucrose diet (HFHSD). However, constitutive BBSome deficiency caused impairment in glucose tolerance and insulin sensitivity. Similar phenotypes were observed after inducible adipocyte-specific disruption of the BBSome (AdipoCreERT2/Bbs1fl/fl mice). Interestingly, a significant increase in renal sympathetic nerve activity, measured using multifiber recording in the conscious state, was observed in AdipoCre/Bbs1fl/fl mice on both chow and HFHSD. A significant increase in tail-cuff arterial pressure was also observed in chow-fed AdipoCre/Bbs1fl/fl mice, but this was not reproduced when arterial pressure was measured by radiotelemetry. Moreover, AdipoCre/Bbs1fl/fl mice had no significant alterations in vascular reactivity. On the other hand, AdipoCre/Bbs1fl/fl mice displayed impaired baroreceptor reflex sensitivity when fed HFHSD, but not on normal chow. Taken together, these data highlight the relevance of the adipocyte BBSome for the regulation of glucose homeostasis and sympathetic traffic. The BBSome also contributes to baroreflex sensitivity under HFHSD, but not normal chow.NEW & NOTEWORTHY The current study show how genetic manipulation of fat cells impacts various functions of the body including sensitivity to the hormone insulin.


Assuntos
Adipócitos , Adiponectina , Animais , Adipócitos/metabolismo , Adiponectina/metabolismo , Adiponectina/genética , Camundongos , Resistência à Insulina , Masculino , Obesidade/fisiopatologia , Obesidade/metabolismo , Obesidade/genética , Camundongos Knockout , Sistema Nervoso Simpático/fisiopatologia , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Doenças do Sistema Nervoso Autônomo/genética , Doenças do Sistema Nervoso Autônomo/metabolismo , Síndrome de Bardet-Biedl/genética , Síndrome de Bardet-Biedl/fisiopatologia , Síndrome de Bardet-Biedl/metabolismo , Proteínas Associadas aos Microtúbulos
5.
Psychiatry Res ; 337: 115951, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38735240

RESUMO

Isolation of rodents throughout adolescence is known to induce many behavioral abnormalities which resemble neuropsychiatric disorders. Separately, this paradigm has also been shown to induce long-term metabolic changes consistent with a pre-diabetic state. Here, we investigate changes in central serotonin (5-HT) and glucagon-like peptide 1 (GLP-1) neurobiology that dually accompany behavioral and metabolic outcomes following social isolation stress throughout adolescence. We find that adolescent-isolation mice exhibit elevated blood glucose levels, impaired peripheral insulin signaling, altered pancreatic function, and fattier body composition without changes in bodyweight. These mice further exhibited disruptions in sleep and enhanced nociception. Using bulk and spatial transcriptomic techniques, we observe broad changes in neural 5-HT, GLP-1, and appetitive circuits. We find 5-HT neurons of adolescent-isolation mice to be more excitable, transcribe fewer copies of Glp1r (mRNA; GLP-1 receptor), and demonstrate resistance to the inhibitory effects of the GLP-1R agonist semaglutide on action potential thresholds. Surprisingly, we find that administration of semaglutide, commonly prescribed to treat metabolic syndrome, induced deficits in social interaction in group-housed mice and rescued social deficits in isolated mice. Overall, we find that central 5-HT circuitry may simultaneously influence mental well-being and metabolic health in this model, via interactions with GLP-1 and proopiomelanocortin circuitry.


Assuntos
Modelos Animais de Doenças , Peptídeo 1 Semelhante ao Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1 , Serotonina , Isolamento Social , Animais , Camundongos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Masculino , Serotonina/metabolismo , Transtornos Mentais/metabolismo , Transtornos Mentais/tratamento farmacológico , Camundongos Endogâmicos C57BL , Doenças Metabólicas/metabolismo , Doenças Metabólicas/fisiopatologia , Glicemia/metabolismo , Glicemia/efeitos dos fármacos
6.
Eur J Appl Physiol ; 124(7): 2209-2223, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38441691

RESUMO

INTRODUCTION: Strength training mitigates the age-related decline in strength and muscle activation but limited evidence exists on specific motor pathway adaptations. METHODS: Eleven young (22-34 years) and ten older (66-80 years) adults underwent five testing sessions where lumbar-evoked potentials (LEPs) and motor-evoked potentials (MEPs) were measured during 20 and 60% of maximum voluntary contraction (MVC). Ten stimulations, randomly delivered, targeted 25% of maximum compound action potential for LEPs and 120, 140, and 160% of active motor threshold (aMT) for MEPs. The 7-week whole-body resistance training intervention included five exercises, e.g., knee extension (5 sets) and leg press (3 sets), performed twice weekly and was followed by 4 weeks of detraining. RESULTS: Young had higher MVC (~ 63 N·m, p = 0.006), 1-RM (~ 50 kg, p = 0.002), and lower aMT (~ 9%, p = 0.030) than older adults at baseline. Young increased 1-RM (+ 18 kg, p < 0.001), skeletal muscle mass (SMM) (+ 0.9 kg, p = 0.009), and LEP amplitude (+ 0.174, p < 0.001) during 20% MVC. Older adults increased MVC (+ 13 N·m, p = 0.014), however, they experienced decreased LEP amplitude (- 0.241, p < 0.001) during 20% MVC and MEP amplitude reductions at 120% (- 0.157, p = 0.034), 140% (- 0.196, p = 0.026), and 160% (- 0.210, p = 0.006) aMT during 60% MVC trials. After detraining, young and older adults decreased 1-RM, while young adults decreased SMM. CONCLUSION: Higher aMT and MEP amplitude in older adults were concomitant with lower baseline strength. Training increased strength in both groups, but divergent modifications in cortico-spinal activity occurred. Results suggest that the primary locus of adaptation occurs at the spinal level.


Assuntos
Potencial Evocado Motor , Músculo Quadríceps , Treinamento Resistido , Humanos , Treinamento Resistido/métodos , Idoso , Masculino , Adulto , Feminino , Potencial Evocado Motor/fisiologia , Músculo Quadríceps/fisiologia , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Adaptação Fisiológica/fisiologia , Adulto Jovem , Força Muscular/fisiologia , Córtex Motor/fisiologia , Contração Muscular/fisiologia , Medula Espinal/fisiologia
7.
Function (Oxf) ; 5(1): zqad070, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38223458

RESUMO

The BBSome, a complex of several Bardet-Biedl syndrome (BBS) proteins including BBS1, has emerged as a critical regulator of energy homeostasis. Although the BBSome is best known for its involvement in cilia trafficking, through a process that involve BBS3, it also regulates the localization of cell membrane receptors underlying metabolic regulation. Here, we show that inducible Bbs1 gene deletion selectively in proopiomelanocortin (POMC) neurons cause a gradual increase in body weight, which was associated with higher fat mass. In contrast, inducible deletion of Bbs3 gene in POMC neurons failed to affect body weight and adiposity. Interestingly, loss of BBS1 in POMC neurons led to glucose intolerance and insulin insensitivity, whereas BBS3 deficiency in these neurons is associated with slight impairment in glucose handling, but normal insulin sensitivity. BBS1 deficiency altered the plasma membrane localization of serotonin 5-HT2C receptor (5-HT2CR) and ciliary trafficking of neuropeptide Y2 receptor (NPY2R).In contrast, BBS3 deficiency, which disrupted the ciliary localization of the BBSome, did not interfere with plasma membrane expression of 5-HT2CR, but reduced the trafficking of NPY2R to cilia. We also show that deficiency in BBS1, but not BBS3, alters mitochondria dynamics and decreased total and phosphorylated levels of dynamin-like protein 1 (DRP1) protein. Importantly, rescuing DRP1 activity restored mitochondria dynamics and localization of 5-HT2CR and NPY2R in BBS1-deficient cells. The contrasting effects on energy and glucose homeostasis evoked by POMC neuron deletion of BBS1 versus BBS3 indicate that BBSome regulation of metabolism is not related to its ciliary function in these neurons.


Assuntos
Síndrome de Bardet-Biedl , Peso Corporal , Cílios , Pró-Opiomelanocortina , Humanos , Cílios/genética , Glucose/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Neurônios/metabolismo , Pró-Opiomelanocortina/genética , Transporte Proteico/genética , Serotonina/metabolismo , Animais
8.
Am J Physiol Endocrinol Metab ; 325(6): E711-E722, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37909854

RESUMO

The BBSome is a protein complex composed of eight Bardet-Biedl syndrome (BBS) proteins including BBS1. Humans and mice lacking a functional BBSome display obesity and type 2 diabetes, highlighting the importance of this protein complex for metabolic regulation. However, the contribution of the BBSome in insulin-sensitive tissues such as skeletal muscle and liver to metabolic regulation is ill-defined. Here, we show that disruption of the BBSome through Bbs1 gene deletion in the skeletal muscle had no effect on body weight or glucose handling, but improved insulin sensitivity of female mice without changing insulin receptor signaling. Interestingly, when fed an obesogenic diet, male mice lacking the Bbs1 gene in skeletal muscle exhibited heightened insulin sensitivity despite the comparable weight gain and glucose tolerance relative to controls. On the other hand, normal chow-fed mice missing the Bbs1 gene in hepatocytes displayed increased body weight, as well as impaired glucose handling and insulin sensitivity. This was associated with attenuated insulin signaling in liver and hepatocytes, but not skeletal muscle and white adipose tissue. Moreover, hepatocytes lacking the Bbs1 gene displayed significant reduction in plasma membrane insulin receptor levels due to the mitochondrial dysfunction evoked by loss of the BBSome. Together, these findings demonstrate that myocyte BBSome is minimally involved in metabolic regulation, whereas the hepatic BBSome plays a critical role in the control of energy homeostasis and insulin sensitivity through its requirement for insulin receptor trafficking.NEW & NOTEWORTHY The ongoing epidemic of obesity and associated illnesses highlights the need to understand the biological processes that regulate energy balance. Here, we identified an important role for a protein complex called BBSome in the control of hepatic function. We show that the liver BBSome is necessary to maintain body weight and blood glucose levels due to its requirements to generate energy and detect insulin, a hormone that is essential for metabolic regulation.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Insulinas , Humanos , Camundongos , Masculino , Feminino , Animais , Proteínas Associadas aos Microtúbulos/metabolismo , Receptor de Insulina , Resistência à Insulina/genética , Diabetes Mellitus Tipo 2/genética , Obesidade/genética , Obesidade/metabolismo , Peso Corporal/genética , Fígado/metabolismo , Glucose , Músculo Esquelético/metabolismo
9.
Cell Rep ; 42(12): 113473, 2023 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-37980562

RESUMO

In the human fungal pathogen Candida albicans, invasive hyphal growth is a well-recognized virulence trait. We employed transposon-mediated genome-wide mutagenesis, revealing that inactivating CTM1 blocks hyphal growth. CTM1 encodes a lysine (K) methyltransferase, which trimethylates cytochrome c (Cyc1) at K79. Mutants lacking CTM1 or expressing cyc1K79A grow as yeast under hyphae-inducing conditions, indicating that unmethylated Cyc1 suppresses hyphal growth. Transcriptomic analyses detected increased levels of the hyphal repressor NRG1 and decreased levels of hyphae-specific genes in ctm1Δ/Δ and cyc1K79A mutants, suggesting cyclic AMP (cAMP)-protein kinase A (PKA) signaling suppression. Co-immunoprecipitation and in vitro kinase assays demonstrated that unmethylated Cyc1 inhibits PKA kinase activity. Surprisingly, hyphae-defective ctm1Δ/Δ and cyc1K79A mutants remain virulent in mice due to accelerated proliferation. Our results unveil a critical role for cytochrome c in maintaining the virulence of C. albicans by orchestrating proliferation, growth mode, and metabolism. Importantly, this study identifies a biological function for lysine methylation on cytochrome c.


Assuntos
Candida albicans , Proteínas Fúngicas , Animais , Camundongos , Humanos , Candida albicans/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , AMP Cíclico/metabolismo , Citocromos c/metabolismo , Hifas , Lisina/metabolismo , Morfogênese , Regulação Fúngica da Expressão Gênica
10.
Front Microbiol ; 14: 1209067, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37469436

RESUMO

Psychobiotics are a class of probiotics that confer beneficial effects on the mental health of the host. We have previously reported hypnotic effects of a psychobiotic strain, Lactobacillus fermentum PS150 (PS150), which significantly shortens sleep latency in experimental mice, and effectively ameliorate sleep disturbances caused by either caffeine consumption or a novel environment. In the present study, we discovered a L. fermentum strain, GR1009, isolated from the same source of PS150, and found that GR1009 is phenotypically distinct but genetically similar to PS150. Compared with PS150, GR1009 have no significant hypnotic effects in the pentobarbital-induced sleep test in mice. In addition, we found that heat-killed PS150 exhibited hypnotic effects and altered the gut microbiota in a manner similar to live bacteria, suggesting that a heat-stable effector, such as exopolysaccharide (EPS), could be responsible for these effects. Our comparative genomics analysis also revealed distinct genetic characteristics in EPS biosynthesis between GR1009 and PS150. Furthermore, scanning electron microscopy imaging showed a sheet-like EPS structure in PS150, while GR1009 displayed no apparent EPS structure. Using the phenol-sulfate assay, we found that the sugar content value of the crude extract containing EPS (C-EPS) from PS150 was approximately five times higher than that of GR1009, indicating that GR1009 has a lower EPS production activity than PS150. Through the pentobarbital-induced sleep test, we confirmed the hypnotic effects of the C-EPS isolated from PS150, as evidenced by a significant reduction in sleep latency and recovery time following oral administration in mice. In summary, we utilized a comparative approach to delineate differences between PS150 and GR1009 and proposed that EPS may serve as a key factor that mediates the observed hypnotic effect.

11.
bioRxiv ; 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37398179

RESUMO

In 2020, stay-at-home orders were implemented to stem the spread of SARS-CoV-2 worldwide. Social isolation can be particularly harmful to children and adolescents-during the pandemic, the prevalence of obesity increased by ∼37% in persons aged 2-19. Obesity is often comorbid with type 2 diabetes, which was not assessed in this human pandemic cohort. Here, we investigated whether male mice isolated throughout adolescence develop type 2 diabetes in a manner consistent with human obesity-induced diabetes, and explored neural changes that may underlie such an interaction. We find that isolating C57BL/6J mice throughout adolescence is sufficient to induce type 2 diabetes. We observed fasted hyperglycemia, diminished glucose clearance in response to an insulin tolerance test, decreased insulin signaling in skeletal muscle, decreased insulin staining of pancreatic islets, increased nociception, and diminished plasma cortisol levels compared to group-housed control mice. Using Promethion metabolic phenotyping chambers, we observed dysregulation of sleep and eating behaviors, as well as a time-dependent shift in respiratory exchange ratio of the adolescent-isolation mice. We profiled changes in neural gene transcription from several brain areas and found that a neural circuit between serotonin-producing and GLP-1-producing neurons is affected by this isolation paradigm. Overall, spatial transcription data suggest decreased serotonin neuron activity (via decreased GLP-1-mediated excitation) and increased GLP-1 neuron activity (via decreased serotonin-mediated inhibition). This circuit may represent an intersectional target to further investigate the relationship between social isolation and type 2 diabetes, as well as a pharmacologically-relevant circuit to explore the effects of serotonin and GLP-1 receptor agonists. Article Highlights: Isolating C57BL/6J mice throughout adolescence is sufficient to induce type 2 diabetes, presenting with fasted hyperglycemia.Adolescent-isolation mice have deficits in insulin responsiveness, impaired peripheral insulin signaling, and decreased pancreatic insulin production.Transcriptional changes across the brain include the endocannabinoid, serotonin, and GLP-1 neurotransmitters and associated receptors. The neural serotonin/GLP-1 circuit may represent an intersectional target to further investigate the relationship between social isolation and type 2 diabetes. Serotonin-producing neurons of adolescent-isolation mice produce fewer transcripts for the GLP-1 receptor, and GLP-1 neurons produce fewer transcripts for the 5-HT 1A serotonin receptor.

12.
Nat Commun ; 14(1): 3433, 2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37301939

RESUMO

High quality(Q) factor optical resonators are indispensable for many photonic devices. While very large Q-factors can be obtained theoretically in guided-mode settings, free-space implementations suffer from various limitations on the narrowest linewidth in real experiments. Here, we propose a simple strategy to enable ultrahigh-Q guided-mode resonances by introducing a patterned perturbation layer on top of a multilayer-waveguide system. We demonstrate that the associated Q-factors are inversely proportional to the perturbation squared while the resonant wavelength can be tuned through material or structural parameters. We experimentally demonstrate such high-Q resonances at telecom wavelengths by patterning a low-index layer on top of a 220 nm silicon on insulator substrate. The measurements show Q-factors up to 2.39 × 105, comparable to the largest Q-factor obtained by topological engineering, while the resonant wavelength is tuned by varying the lattice constant of the top perturbation layer. Our results hold great promise for exciting applications like sensors and filters.


Assuntos
Engenharia , Fótons , Silício , Vibração
13.
Opt Lett ; 48(11): 2881-2884, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37262234

RESUMO

We report on the proof-of-principle experiment of generating carrier-envelope phase (CEP)-controllable and frequency-tunable narrowband terahertz (THz) radiation from an air-plasma filament prescribed by the beat of a temporally stretched two-color laser pulse sequence. The pulse sequence was prepared by propagating the fundamental ultrafast laser pulse through a grating stretcher and Michelson interferometer with variable inter-arm delay. By partially frequency-doubling and focusing the pulse sequence, an air-plasma filament riding a beat note was created to radiate a THz wave with primary pulse characteristics (center frequency and CEP) under coherent control. To reproduce experimental results and elucidate complex nonlinear light-matter interaction, numerical simulation has been performed. This work demonstrates the feasibility of generating coherently controlled narrowband THz wave with high tunability in laser-induced air plasma.

14.
Fitoterapia ; 168: 105553, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37257697

RESUMO

Three undescribed lignan glycosides, echiunines E-G (1-3), as well as eight known compounds (4-11) were isolated from Fritillaria verticillata Willd. Among them, compounds 1-3 were a series of lignan glycosides reported for the first time from genus Fritillaria. Their structures were elucidated by analyses of extensive spectroscopic data and comparison of the NMR data with those reported previously, the absolute configuration of compounds were further confirmed by calculated ECD method. The NO release inhibitory effects of compounds were evaluated in LPS-activated RAW264.7 macrophages. Compounds 7-8 showed inhibitory acitivities in a dose-dependent manner.


Assuntos
Fritillaria , Lignanas , Lignanas/farmacologia , Lignanas/química , Estrutura Molecular , Glicosídeos/farmacologia , Glicosídeos/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química
15.
J Colloid Interface Sci ; 644: 157-166, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37105039

RESUMO

Solar interfacial steam power generation is a prospective method for seawater desalination. In this work, a salt-blocking three-dimensional (3D) Janus evaporator with a superhydrophobic to superhydrophilic gradient was fabricated by spraying a composite dispersion of multi-walled carbon nanotubes/polydimethylsiloxane (CNTs/PDMS) onto the top side of a polyurethane (PU) foam and polyvinyl alcohol (PVA) solution onto the bottom side. The CNTs/PDMS composite dispersion with nanostructured CNTs and low surface energy PDMS combined with the porous structure of the PU foam rendered the top side superhydrophobic. Therefore, a layer suitable for photothermal conversion was obtained. The hydrophilic PVA combined with the porous structure of the foam rendered the bottom side superhydrophilic, facilitating water absorption and transportation. The asymmetric wettability gradient of the CNTs/PDMS-PU-PVA as a 3D evaporator caused the evaporation rate and transportation speed of water to reach a balance, and the salt was quickly dissolved at the superhydrophilic interface. This 3D salt-resistant Janus evaporator achieved an evaporation rate of 2.26 kg m-2 h-1 under 1 kW m-2 illumination.

16.
World J Gastroenterol ; 29(12): 1765-1778, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37032731

RESUMO

Nonalcoholic fatty liver disease (NAFLD) or metabolic-associated fatty liver disease has been characterized by the lipid accumulation with injury of hepatocytes and has become one of the most common chronic liver diseases in the world. The complex mechanisms of NAFLD formation are still under identification. Carnitine palmitoyltransferase-II (CPT-II) on inner mitochondrial membrane (IMM) regulates long chain fatty acid ß-oxidation, and its abnormality has had more and more attention paid to it by basic and clinical research in NAFLD. The sequences of its peptide chain and DNA nucleotides have been identified, and the catalytic activity of CPT-II is affected on its gene mutations, deficiency, enzymatic thermal instability, circulating carnitine level and so on. Recently, the CPT-II dysfunction has been discovered in models of liver lipid accumulation. Meanwhile, the malignant transformation of hepatocyte-related CD44+ stem T cell activation, high levels of tumor-related biomarkers (AFP, GPC3) and abnormal activation of Wnt3a expression as a key signal molecule of the Wnt/ß-catenin pathway run parallel to the alterations of hepatocyte pathology. This review focuses on some of the progress of CPT-II inactivity on IMM with liver fatty accumulation as a possible novel pathogenesis for NAFLD in hepatocarcinogenesis.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Fígado/metabolismo , Carcinogênese/metabolismo , Ácidos Graxos/metabolismo , Oxirredução , Carnitina/metabolismo , Glipicanas/metabolismo
17.
Lipids Health Dis ; 22(1): 34, 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36882763

RESUMO

The miRNA-181 (miR-181) family regulates neuronal persistence during cerebral ischemia/reperfusion injury (CI/RI). Since the effect of miR-181d on CI/RI has never been studied, the current work sought to determine the involvement of miR-181d in neuronal apoptosis after brain I/R injury. To replicate in vivo and in vitro CI/RI, a transient middle cerebral artery occlusion (tMCAO) model in rats and an oxygen-glucose deficiency/reoxygenation (OGD/R) model in neuro 2A cells were developed. In both in vivo and in vitro stroke models, the expression of miR-181d was considerably higher. miR-181d suppression reduced apoptosis and oxidative stress in OGD/R-treated neuroblastoma cells, but miR-181d overexpression increased both. Furthermore, it was observed that miR-181d has a direct target in dedicator of cytokinesis 4 (DOCK4). The overexpression of DOCK4 partially overcame cell apoptosis and oxidative stress induced by miR-181d upregulation and OGD/R injury. Furthermore, the DOCK4 rs2074130 mutation was related to lower DOCK4 levels in ischemic stroke (IS) peripheral blood and higher susceptibility to IS. These findings suggest that downregulating miR-181d protects neurons from ischemic damage by targeting DOCK4, implying that the miR-181d/DOCK4 axis might be a novel therapeutic target for IS.


Assuntos
Lesões Encefálicas , Proteínas Ativadoras de GTPase , AVC Isquêmico , MicroRNAs , Traumatismo por Reperfusão , Animais , Ratos , Citocinese , Glucose , Hipóxia , MicroRNAs/genética , Neurônios , Oxigênio , Traumatismo por Reperfusão/genética , Proteínas Ativadoras de GTPase/genética
18.
JCI Insight ; 8(6)2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36787197

RESUMO

The molecular clock machinery regulates several homeostatic rhythms, including glucose metabolism. We previously demonstrated that Roux-en-Y gastric bypass (RYGB) has a weight-independent effect on glucose homeostasis and transiently reduces food intake. In this study we investigate the effects of RYGB on diurnal eating behavior as well as on the molecular clock and this clock's requirement for the metabolic effects of this bariatric procedure in obese mice. We find that RYGB reversed the high-fat diet-induced disruption in diurnal eating pattern during the early postsurgery phase of food reduction. Dark-cycle pair-feeding experiments improved glucose tolerance to the level of bypass-operated animals during the physiologic fasting phase (Zeitgeber time 2, ZT2) but not the feeding phase (ZT14). Using a clock gene reporter mouse model (mPer2Luc), we reveal that RYGB induced a liver-specific phase shift in peripheral clock oscillation with no changes to the central clock activity within the suprachiasmatic nucleus. In addition, we show that weight loss effects were attenuated in obese ClockΔ19 mutant mice after RYGB that also failed to improve glucose metabolism after surgery, specifically hepatic glucose production. We conclude that RYGB reprograms the peripheral clock within the liver early after surgery to alter diurnal eating behavior and regulate hepatic glucose flux.


Assuntos
Derivação Gástrica , Resistência à Insulina , Camundongos , Animais , Glucose/metabolismo , Derivação Gástrica/métodos , Glicemia/metabolismo , Resistência à Insulina/fisiologia , Comportamento Alimentar , Fígado/metabolismo
19.
ACS Appl Mater Interfaces ; 15(3): 4612-4622, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36631727

RESUMO

The mechanical durability of superhydrophobic surfaces is of significance for their practical applications. However, few reports about superhydrophobic coating on certain substrates took into consideration both the mechanical stability of the superhydrophobic coating and adhesion stability between the coating and the substrate. Herein, we put forward a facile and efficient strategy to construct robust superhydrophobic coatings by simply spray-coating a composite suspension of SiO2 nanoparticles, polydimethylsiloxane (PDMS), and epoxy resin (EP) on substrates pretreated with an EP base-coating. The as-obtained coating exhibited excellent superhydrophobicity with water contact angle of 163° and sliding angle of 3.5°, which could endure UV irradiation of 180 h, immersion in acidic or basic solutions for 168 h, and outdoor exposure for over 30 days. Notably, the coating surface retained superhydrophobicity after being successively impacted with faucet water for 1 h, impinged with 360 g sand grains, and abraded with sandpaper of 120 grid under a load of 500 g for 5 m distance. The outstanding mechanical stability was mainly attributed to the cross-linking of EP and the elastic nature of PDMS which ensured strong cohesion inside the whole coating and to the substrate. Additionally, the coating showed self-healing capacity against O2 plasma etching. The method is simple with the materials commercially available and is expected to be widely applied in outdoor applications.

20.
Am J Physiol Regul Integr Comp Physiol ; 324(2): R161-R170, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36534590

RESUMO

Bsardet Biedl syndrome (BBS) is a genetic condition associated with various clinical features including cutaneous disorders and certain autoimmune and inflammatory diseases pointing to a potential role of BBS proteins in the regulation of immune function. BBS1 protein, which is a key component of the BBSome, a protein complex involved in the regulation of cilia function and other cellular processes, has been implicated in the immune synapse assembly by promoting the centrosome polarization to the antigen-presenting cells. Here, we assessed the effect of disrupting the BBSome, through Bbs1 gene deletion, in T cells. Interestingly, mice lacking the Bbs1 gene specifically in T cells (T-BBS1-/-) displayed normal body weight, adiposity, and glucose handling, but have smaller spleens. However, T-BBS1-/- mice had no change in the proportion and absolute number of B cells and T cells in the spleen and lymph nodes. There was also no alteration in the CD4/CD8 lineage commitment or survival in the thymus of T-BBS1-/- mice. On the other hand, T-BBS1-/- mice treated with Imiquimod dermally exhibited a significantly higher percentage of CD3-positive splenocytes that was due to CD4 but not CD8 T cell predominance. Notably, we found that T-BBS1-/- mice had significantly decreased wound closure, an effect that was more pronounced in males indicating that the BBSome plays an important role in T cell-mediated skin repair. Together, these findings implicate the BBSome in the regulation of selective functions of T cells.


Assuntos
Cílios , Proteínas Associadas aos Microtúbulos , Animais , Masculino , Camundongos , Adiposidade , Cílios/metabolismo , Cílios/patologia , Imunidade/genética , Proteínas Associadas aos Microtúbulos/genética , Síndrome de Bardet-Biedl/genética , Síndrome de Bardet-Biedl/metabolismo
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