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1.
J Transl Med ; 22(1): 375, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643121

RESUMO

Maladaptive cardiac hypertrophy contributes to the development of heart failure (HF). The oxidoreductase Selenoprotein T (SELENOT) emerged as a key regulator during rat cardiogenesis and acute cardiac protection. However, its action in chronic settings of cardiac dysfunction is not understood. Here, we investigated the role of SELENOT in the pathophysiology of HF: (i) by designing a small peptide (PSELT), recapitulating SELENOT activity via the redox site, and assessed its beneficial action in a preclinical model of HF [aged spontaneously hypertensive heart failure (SHHF) rats] and against isoproterenol (ISO)-induced hypertrophy in rat ventricular H9c2 and adult human AC16 cardiomyocytes; (ii) by evaluating the SELENOT intra-cardiomyocyte production and secretion under hypertrophied stimulation. Results showed that PSELT attenuated systemic inflammation, lipopolysaccharide (LPS)-induced macrophage M1 polarization, myocardial injury, and the severe ultrastructural alterations, while counteracting key mediators of cardiac fibrosis, aging, and DNA damage and restoring desmin downregulation and SELENOT upregulation in the failing hearts. In the hemodynamic assessment, PSELT improved the contractile impairment at baseline and following ischemia/reperfusion injury, and reduced infarct size in normal and failing hearts. At cellular level, PSELT counteracted ISO-mediated hypertrophy and ultrastructural alterations through its redox motif, while mitigating ISO-triggered SELENOT intracellular production and secretion, a phenomenon that presumably reflects the extent of cell damage. Altogether, these results indicate that SELENOT could represent a novel sensor of hypertrophied cardiomyocytes and a potential PSELT-based new therapeutic approach in myocardial hypertrophy and HF.


Assuntos
Insuficiência Cardíaca , Humanos , Adulto , Ratos , Animais , Idoso , Insuficiência Cardíaca/metabolismo , Miócitos Cardíacos/metabolismo , Isoproterenol/metabolismo , Isoproterenol/farmacologia , Oxirredução , Hipertrofia/metabolismo , Selenoproteínas/metabolismo , Selenoproteínas/farmacologia
2.
PLoS One ; 19(4): e0301496, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635745

RESUMO

Obesity leads to insulin resistance (IR) and type 2 diabetes. In humans, low levels of the hormone prolactin (PRL) correlate with IR, adipose tissue (AT) dysfunction, and increased prevalence of T2D. In obese rats, PRL treatment promotes insulin sensitivity and reduces visceral AT adipocyte hypertrophy. Here, we tested whether elevating PRL levels with the prokinetic and antipsychotic drug sulpiride, an antagonist of dopamine D2 receptors, improves metabolism in high fat diet (HFD)-induced obese male mice. Sulpiride treatment (30 days) reduced hyperglycemia, IR, and the serum and pancreatic levels of triglycerides in obese mice, reduced visceral and subcutaneous AT adipocyte hypertrophy, normalized markers of visceral AT function (PRL receptor, Glut4, insulin receptor and Hif-1α), and increased glycogen stores in skeletal muscle. However, the effects of sulpiride reducing hyperglycemia were also observed in obese prolactin receptor null mice. We conclude that sulpiride reduces obesity-induced hyperglycemia by mechanisms that are independent of prolactin/prolactin receptor activity. These findings support the therapeutic potential of sulpiride against metabolic dysfunction in obesity.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Resistência à Insulina , Humanos , Camundongos , Masculino , Ratos , Animais , Camundongos Obesos , Antagonistas dos Receptores de Dopamina D2 , Prolactina , Receptores da Prolactina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Sulpirida/farmacologia , Sulpirida/uso terapêutico , Obesidade/tratamento farmacológico , Obesidade/etiologia , Dieta Hiperlipídica/efeitos adversos , Hiperglicemia/tratamento farmacológico , Hipertrofia , Insulina/metabolismo
3.
Cell Rep ; 43(4): 114052, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38573860

RESUMO

Skeletal muscles exert remarkable regenerative or adaptive capacities in response to injuries or mechanical loads. However, the cellular networks underlying muscle adaptation are poorly understood compared to those underlying muscle regeneration. We employed single-cell RNA sequencing to investigate the gene expression patterns and cellular networks activated in overloaded muscles and compared these results with those observed in regenerating muscles. The cellular composition of the 4-day overloaded muscle, when macrophage infiltration peaked, closely resembled that of the 10-day regenerating muscle. In addition to the mesenchymal progenitor-muscle satellite cell (MuSC) axis, interactome analyses or targeted depletion experiments revealed communications between mesenchymal progenitors-macrophages and macrophages-MuSCs. Furthermore, granulin, a macrophage-derived factor, inhibited MuSC differentiation, and Granulin-knockout mice exhibited blunted muscle hypertrophy due to the premature differentiation of overloaded MuSCs. These findings reveal the critical role of granulin through the relayed communications of mesenchymal progenitors, macrophages, and MuSCs in facilitating efficient muscle hypertrophy.


Assuntos
Diferenciação Celular , Hipertrofia , Macrófagos , Células-Tronco Mesenquimais , Camundongos Knockout , Células Satélites de Músculo Esquelético , Animais , Células Satélites de Músculo Esquelético/metabolismo , Células Satélites de Músculo Esquelético/patologia , Macrófagos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Granulinas , Comunicação Celular , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Masculino , Regeneração
4.
J Int Med Res ; 52(4): 3000605241233141, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38629479

RESUMO

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by massive lymphadenopathy and systemic extranodal lesions. We present the case of a 28-year-old woman who presented with recurrent blurred vision in her right eye for 3 months. She developed blindness and atrophy in her left eye a decade prior to presentation. She subsequently developed headache, fever, and impaired mental status. Cranial magnetic resonance imaging indicated hypertrophic pachymeningitis (HP), and 18F-fluoro-2-deoxy-2-d-glucose (FDG) positron emission tomography/computed tomography revealed significant FDG uptake in the left dura mater. Autoimmune testing revealed elevated anti-nuclear, anti-SS-A, and anti-SS-B antibody levels. Incisional biopsy of the atrophic eyeball revealed RDD with marked polyclonal plasmacytosis. The patient was diagnosed with RDD accompanied by multisystem involvement, including Sjögren's syndrome (SS), panuveitis, and HP. Treatment with methylprednisolone for several weeks resulted in significant improvement. This is the first reported case of RDD presenting with SS in combination with panuveitis and HP. Although RDD is rarely diagnosed in young patients, interdisciplinary collaboration is essential to prevent a delayed diagnosis.


Assuntos
Histiocitose Sinusal , Pan-Uveíte , Síndrome de Sjogren , Humanos , Feminino , Adulto , Histiocitose Sinusal/complicações , Histiocitose Sinusal/diagnóstico , Histiocitose Sinusal/patologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Hipertrofia , Pan-Uveíte/complicações , Pan-Uveíte/diagnóstico , Pan-Uveíte/tratamento farmacológico
5.
Biochemistry (Mosc) ; 89(Suppl 1): S1-S13, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38621741

RESUMO

Circular RNAs (circRNAs) are a large class of endogenous single-stranded covalently closed RNA molecules. High-throughput RNA sequencing and bioinformatic algorithms have identified thousands of eukaryotic circRNAs characterized by high stability and tissue-specific expression pattern. Recent studies have shown that circRNAs play an important role in the regulation of physiological processes in the norm and in various diseases, including cardiovascular disorders. The review presents current concepts of circRNA biogenesis, structural features, and biological functions, describes the methods of circRNA analysis, and summarizes the results of studies on the role of circRNAs in the pathogenesis of hypertrophic cardiomyopathy, the most common inherited heart disease.


Assuntos
Cardiomiopatia Hipertrófica , RNA Circular , Humanos , RNA Circular/genética , RNA/genética , RNA/metabolismo , Hipertrofia
6.
Zhongguo Zhong Yao Za Zhi ; 49(3): 754-762, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621879

RESUMO

This study aims to explore the mechanism of Linggui Zhugan Decoction(LGZGD) in inhibiting Angiotensin Ⅱ(AngⅡ)-induced cardiomyocyte hypertrophy by regulating sigma-1 receptor(Sig1R). The model of H9c2 cardiomyocyte hypertrophy induced by AngⅡ in vitro was established by preparing LGZGD-containing serum and blank serum. H9c2 cells were divided into normal group, AngⅡ model group, 20% normal rat serum group(20% NSC), and 20% LGZGD-containing serum group. After the cells were incubated with AngⅡ(1 µmol·L~(-1)) or AngⅡ with serum for 72 h, the surface area of cardiomyocytes was detected by phalloidine staining, and the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase were detected by micromethod. The mitochondrial Ca~(2+) levels were detected by flow cytometry, and the expression levels of atrial natriuretic peptide(ANP), brain natriuretic peptide(BNP), Sig1R, and inositol 1,4,5-triphosphate receptor type 2(IP_3R_2) were detected by Western blot. The expression of Sig1R was down-regulated by transfecting specific siRNA for investigating the efficacy of LGZGD-containing serum on cardiomyocyte surface area, Na~+-K~+-ATPase activity, Ca~(2+)-Mg~(2+)-ATPase activity, mitochondrial Ca~(2+), as well as ANP, BNP, and IP_3R_2 protein expressions. The results showed that compared with the normal group, AngⅡ could significantly increase the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.01), and it could decrease the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+), and the expression of Sig1R(P<0.01). In addition, IP_3R_2 protein expression was significantly increased(P<0.01). LGZGD-containing serum could significantly decrease the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.05, P<0.01), and it could increase the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+ )(P<0.01), and the expression of Sig1R(P<0.05). In addition, IP_3R_2 protein expression was significantly decreased(P<0.05). However, after Sig1R was down-regulated, the effects of LGZGD-containing serum were reversed(P<0.01). These results indicated that the LGZGD-containing serum could inhibit cardiomyocyte hypertrophy induced by AngⅡ, and its pharmacological effect was related to regulating Sig1R, promoting mitochondrial Ca~(2+ )inflow, restoring ATP synthesis, and protecting mitochondrial function.


Assuntos
Miócitos Cardíacos , ATPase Trocadora de Sódio-Potássio , Ratos , Animais , Células Cultivadas , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Angiotensina II/efeitos adversos , Angiotensina II/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Hipertrofia/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/tratamento farmacológico , Cardiomegalia/genética
7.
S Afr J Surg ; 62(1): 89-91, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38568134

RESUMO

SUMMARY: Gestational gigantomastia is a rare condition typified by disproportionate bilateral breast enlargement in pregnant women, resulting in skin thinning, ulceration, and bleeding. Less than sixty cases have been documented worldwide, and only one other in South Africa. Pseudo-angiomatous stromal hyperplasia (PASH) is a rare benign proliferation of stromal tissue in a tumorous or diffuse pattern. This, to the best of our knowledge, is the first published case, a 27-year-old human immunodeficiency virus (HIV) positive woman, to present with both conditions concurrently. Medical management with cabergoline was initiated and, seven months post-delivery, a novel Goldilocks mastectomy was performed with acceptable outcomes.


Assuntos
Neoplasias da Mama , Mama/anormalidades , Soropositividade para HIV , Hipertrofia , Gravidez , Feminino , Humanos , Adulto , Hiperplasia/complicações , Mastectomia
8.
Ann Plast Surg ; 92(4S Suppl 2): S293-S297, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38556692

RESUMO

INTRODUCTION: Pediatric reduction mammoplasty has become increasingly common due to the obesity epidemic. While obesity remains the leading cause of macromastia leading to surgery, it may also be a risk factor for postoperative complications. This study examines the safety of pediatric reduction mammoplasty and the risk of obesity for complications following this procedure. METHODS: The American College of Surgeons National Surgical Quality Improvement Program Pediatrics was queried to obtain all reduction mammoplasty cases from 2012 to 2020. Univariate and multivariate logistic regression analyses controlling for confounders were carried out to assess the relationship between body mass index (BMI) and rates of complication. RESULTS: One thousand five hundred eighty-nine patients with the primary Current Procedural Terminology code 19318 were included in the final analysis. The mean age was 16.6 (SD, 1.1) years, and the mean BMI was 30.5 (SD, 6.2) lb/in2. Notably, 49% of the patients were obese, and 31% were overweight, while only 0.4% were underweight. Forty-three patients (2.7%) sustained a superficial surgical site infection (SSI) postoperatively. Other complications were less prevalent, including deep SSI (4 patients, 0.3%), dehiscence (11, 0.7%), reoperation (21, 1%), and readmission (26, 1.6%).Independent variables analyzed included age, sex, BMI, diabetes mellitus, American Society of Anesthesiologists (ASA) class, and operative time, of which only BMI and ASA class were found to be significantly associated with SSI on univariate analysis. On multivariate logistic regression while controlling for ASA class and the false discovery rate, there was a strong association between increasing rates of superficial SSI and increasing BMI (unit odds ratio, 1.05; 95% confidence interval, [1.01, 1.09]; P = 0.02). The OR indicates that for each 1-unit increase in BMI, the odds of SSI increase by 5%. CONCLUSIONS: Complications following pediatric reduction mammoplasty are uncommon, demonstrating the safety of this procedure. High BMI was found to have a significantly higher risk for superficial SSI. Increased caution and infection prophylaxis should be taken when performing this operation on obese patients.


Assuntos
Mamoplastia , Infecção da Ferida Cirúrgica , Humanos , Criança , Adolescente , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Obesidade/complicações , Obesidade/epidemiologia , Fatores de Risco , Hipertrofia , Mamoplastia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
9.
Int J Mol Sci ; 25(7)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38612868

RESUMO

Natural rare sugars are an alternative category of sweeteners with positive physiologic and metabolic effects both in in vitro and animal models. D-allulose is a D-fructose epimer that combines 70% sucrose sweetness with the advantage of an extremely low energy content. However, there are no data about the effect of D-allulose against adipose dysfunction; thus, it remains to be confirmed whether D-allulose is useful in the prevention and in treatment of adipose tissue alterations. With this aim, we evaluated D-allulose's preventive effects on lipid accumulation in 3T3-L1 murine adipocytes exposed to palmitic acid (PA), a trigger for hypertrophic adipocytes. D-allulose in place of glucose prevented adipocyte hypertrophy and the activation of adipogenic markers C/EBP-ß and PPARγ induced by high PA concentrations. Additionally, D-allulose pretreatment inhibited the NF-κB pathway and endoplasmic reticulum stress caused by PA, through activation of the Nrf2 pathway. Interestingly, these effects were also observed as D-allulose post PA treatment. Although our data need to be confirmed through in vivo models, our findings suggest that incorporating D-allulose as a glucose substitute in the diet might have a protective role in adipocyte function and support a unique mechanism of action in this sugar as a preventive or therapeutic compound against PA lipotoxicity through the modulation of pathways connected to lipid transport and metabolism.


Assuntos
Frutose , Ácido Palmítico , Animais , Camundongos , Ácido Palmítico/toxicidade , Células 3T3-L1 , Adipócitos , Hipertrofia , Estresse do Retículo Endoplasmático , Glucose
10.
Nat Commun ; 15(1): 3216, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622120

RESUMO

Biomolecular condensates, often assembled through phase transition mechanisms, play key roles in organizing diverse cellular activities. The material properties of condensates, ranging from liquid droplets to solid-like glasses or gels, are key features impacting the way resident components associate with one another. However, it remains unclear whether and how different material properties would influence specific cellular functions of condensates. Here, we combine optogenetic control of phase separation with single-molecule mRNA imaging to study relations between phase behaviors and functional performance of condensates. Using light-activated condensation, we show that sequestering target mRNAs into condensates causes translation inhibition. Orthogonal mRNA imaging reveals highly transient nature of interactions between individual mRNAs and condensates. Tuning condensate composition and material property towards more solid-like states leads to stronger translational repression, concomitant with a decrease in molecular mobility. We further demonstrate that ß-actin mRNA sequestration in neurons suppresses spine enlargement during chemically induced long-term potentiation. Our work highlights how the material properties of condensates can modulate functions, a mechanism that may play a role in fine-tuning the output of condensate-driven cellular activities.


Assuntos
Actinas , Optogenética , Humanos , Actinas/genética , Condensados Biomoleculares , Hipertrofia , Potenciação de Longa Duração
11.
Stem Cell Res Ther ; 15(1): 98, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581019

RESUMO

BACKGROUND: In vitro chondrogenesis of mesenchymal stromal cells (MSCs) driven by the essential chondro-inducer transforming growth factor (TGF)-ß is instable and yields undesired hypertrophic cartilage predisposed to bone formation in vivo. TGF-ß can non-canonically activate bone morphogenetic protein-associated ALK1/2/3 receptors. These have been accused of driving hypertrophic MSC misdifferentiation, but data remained conflicting. We here tested the antihypertrophic capacity of two highly specific ALK1/2/3 inhibitors - compound A (CompA) and LDN-212854 (LDN21) - in order to reveal potential prohypertrophic contributions of these BMP/non-canonical TGF-ß receptors during MSC in vitro chondrogenesis. METHODS: Standard chondrogenic pellet cultures of human bone marrow-derived MSCs were treated with TGF-ß and CompA (500 nM) or LDN21 (500 nM). Daily 6-hour pulses of parathyroid hormone-related peptide (PTHrP[1-34], 2.5 nM, from day 7) served as potent antihypertrophic control treatment. Day 28 samples were subcutaneously implanted into immunodeficient mice. RESULTS: All groups underwent strong chondrogenesis, but GAG/DNA deposition and ACAN expression were slightly but significantly reduced by ALK inhibition compared to solvent controls along with a mild decrease of the hypertrophy markers IHH-, SPP1-mRNA, and Alkaline phosphatase (ALP) activity. When corrected for the degree of chondrogenesis (COL2A1 expression), only pulsed PTHrP but not ALK1/2/3 inhibition qualified as antihypertrophic treatment. In vivo, all subcutaneous cartilaginous implants mineralized within 8 weeks, but PTHrP pretreated samples formed less bone and attracted significantly less haematopoietic marrow than ALK1/2/3 inhibitor groups. CONCLUSIONS: Overall, our data show that BMP-ALK1/2/3 inhibition cannot program mesenchymal stromal cells toward stable chondrogenesis. BMP-ALK1/2/3 signalling is no driver of hypertrophic MSC misdifferentiation and BMP receptor induction is not an adverse prohypertrophic side effect of TGF-ß that leads to endochondral MSC misdifferentiation. Instead, the prohypertrophic network comprises misregulated PTHrP/hedgehog signalling and WNT activity, and a potential contribution of TGF-ß-ALK4/5-mediated SMAD1/5/9 signalling should be further investigated to decide about its postulated prohypertrophic activity. This will help to successfully engineer cartilage replacement tissues from MSCs in vitro and translate these into clinical cartilage regenerative therapies.


Assuntos
Células-Tronco Mesenquimais , Proteína Relacionada ao Hormônio Paratireóideo , Animais , Humanos , Camundongos , Células Cultivadas , Condrócitos/metabolismo , Condrogênese , Proteínas Hedgehog/genética , Hipertrofia/metabolismo , Células-Tronco Mesenquimais/metabolismo , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Fator de Crescimento Transformador beta/metabolismo
12.
Sci Rep ; 14(1): 8482, 2024 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605156

RESUMO

Decongestion reduces blood flow in the nasal turbinates, enlarging the airway lumen. Although the enlarged airspace reduces the trans-nasal inspiratory pressure drop, symptoms of nasal obstruction may relate to nasal cavity air-conditioning. Thus, it is necessary to quantify the efficiency of nasal cavity conditioning of the inhaled air. This study quantifies both overall and regional nasal air-conditioning in a cohort of 10 healthy subjects using computational fluid dynamics simulations before and after nasal decongestion. The 3D virtual geometry model was segmented from magnetic resonance images (MRI). Each subject was under two MRI acquisitions before and after the decongestion condition. The effects of decongestion on nasal cavity air conditioning efficiency were modelled at two inspiratory flowrates: 15 and 30 L min-1 to represent restful and light exercise conditions. Results show inhaled air was both heated and humidified up to 90% of alveolar conditions at the posterior septum. The air-conditioning efficiency of the nasal cavity remained nearly constant between nostril and posterior septum but dropped significantly after posterior septum. In summary, nasal cavity decongestion not only reduces inhaled air added heat by 23% and added moisture content by 19%, but also reduces the air-conditioning efficiency by 35% on average.


Assuntos
Cavidade Nasal , Obstrução Nasal , Humanos , Cavidade Nasal/diagnóstico por imagem , Cavidade Nasal/fisiologia , Ar Condicionado , Estudos de Coortes , Conchas Nasais , Hipertrofia , Simulação por Computador
13.
Molecules ; 29(7)2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38611722

RESUMO

Podophyllotoxin, a cyclolignan natural product, has been the object of extensive chemomodulation to obtain better chemotherapeutic agents. Among the obtained podophyllotoxin derivatives, podophyllic aldehyde showed very interesting potency and selectivity against several tumoral cell lines, so it became our lead compound for further modifications, as described in this work, oriented toward the enlargement of the cyclolignan skeleton. Thus, modifications performed at the aldehyde function included nucleophilic addition reactions and the incorporation of the aldehyde carbon into several five-membered rings, such as thiazolidinones and benzo-fused azoles. The synthesized derivatives were evaluated against several types of cancer cells, and although some compounds were cytotoxic at the nanomolar range, most of them were less potent and less selective than the parent compound podophyllic aldehyde, with the most potent being those having the lactone ring of podophyllotoxin. In silico ADME evaluation predicted good druggability for most of them. The results indicate that the γ-lactone ring is important for potency, while the α,ß-unsaturated aldehyde is necessary to induce selectivity in these cyclolignans.


Assuntos
Antineoplásicos , Podofilotoxina , Humanos , Podofilotoxina/farmacologia , Esqueleto , Hipertrofia , Aldeídos , Lactonas , Compostos Radiofarmacêuticos
14.
Curr Med Sci ; 44(2): 450-461, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38639827

RESUMO

OBJECTIVE: Cymbopogon citratus (DC.) Stapf is a medicinal and edible herb that is widely used for the treatment of gastric, nervous and hypertensive disorders. In this study, we investigated the cardioprotective effects and mechanisms of the essential oil, the main active ingredient of Cymbopogon citratus, on isoproterenol (ISO)-induced cardiomyocyte hypertrophy. METHODS: The compositions of Cymbopogon citratus essential oil (CCEO) were determined by gas chromatography-mass spectrometry. Cardiomyocytes were pretreated with 16.9 µg/L CCEO for 1 h followed by 10 µmol/L ISO for 24 h. Cardiac hypertrophy-related indicators and NLRP3 inflammasome expression were evaluated. Subsequently, transcriptome sequencing (RNA-seq) and target verification were used to further explore the underlying mechanism. RESULTS: Our results showed that the CCEO mainly included citronellal (45.66%), geraniol (23.32%), and citronellol (10.37%). CCEO inhibited ISO-induced increases in cell surface area and protein content, as well as the upregulation of fetal gene expression. Moreover, CCEO inhibited ISO-induced NLRP3 inflammasome expression, as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3, ASC, CASP1, GSDMD, and IL-1ß, as well as reduced protein levels of NLRP3, ASC, pro-caspase-1, caspase-1 (p20), GSDMD-FL, GSDMD-N, and pro-IL-1ß. The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated cardiomyocytes. Our further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1, Sdhd, mt-Cytb, Uqcrq, and mt-Atp6 but had no obvious effects on mt-Col expression. CONCLUSION: CCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.


Assuntos
Cymbopogon , Óleos Voláteis , Óleos Voláteis/farmacologia , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Cymbopogon/química , Cymbopogon/metabolismo , Isoproterenol , Miócitos Cardíacos/metabolismo , Fosforilação Oxidativa , RNA Mensageiro/metabolismo , Hipertrofia/induzido quimicamente , Hipertrofia/tratamento farmacológico , Hipertrofia/metabolismo
15.
J Int Med Res ; 52(3): 3000605241233963, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38436326

RESUMO

We herein present a rare case of acute central serous chorioretinopathy (CSC) associated with nonspecific orbital inflammation (NSOI). A 38-year-old woman presented with a 3-day history of ocular pain, reduced vision, periorbital swelling, proptosis, conjunctival chemosis, and restricted eye movements. Optical coherence tomography of the affected eye confirmed signs of CSC. Additionally, a computed tomography scan revealed enlargement of intraconal soft tissues and the lacrimal gland. Ocular ultrasonography detected posterior sclera thickening, indicating posterior scleritis. Following the diagnosis of NSOI, the patient received treatment with systemic corticosteroids, resulting in gradual regression of both the orbital inflammation and CSC. This is the first reported case of localized posterior pole CSC documented in a patient with NSOI. Vigilant monitoring for any ocular disorders is important in patients with orbital inflammation.


Assuntos
Coriorretinopatia Serosa Central , Feminino , Humanos , Adulto , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/diagnóstico por imagem , Inflamação , Olho , Face , Hipertrofia
17.
PeerJ ; 12: e16981, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464759

RESUMO

Background: This study examined the epidemiological correlations between secretory otitis media (SOM) and diseases of neighboring organs. We measured changes in disease incidences during the 2020 COVID-19 pandemic using Internet big data spanning from 2011 to 2021. Methods: This study used the Baidu Index (BI) to determine the search volume for the terms "secretory otitis media (SOM)", "tonsillitis", "pharyngolaryngitis", "adenoid hypertrophy (AH)", "nasopharyngeal carcinoma (NPC)", "nasal septum deviation (NSD)", "rhinosinusitis", "allergic rhinitis (AR)", and "gastroesophageal reflux disease (GERD)" in Mandarin from January 2011 to December 2021. The correlations between these terms were analyzed using Spearman's correlation coefficients. The results were compared search data from 2019 and 2021 to assess the effects of isolation on SOM in 2020. Results: The seasonal variations trends of SOM and other diseases coincided well (P < 0.05), except for AR. During the 11-year timeframe, the monthly searches for rhinosinusitis, NSD, tonsillitis, pharyngolaryngitis, and NPC were statistically correlated with SOM (R = 0.825, 0.594, 0.650, 0.636, 0.664, respectively; P < 0.05). No correlation was found between SOM and AR, SOM and AH, or SOM and GERD (R =  - 0.028, R = 0.259, R = 0.014, respectively, P > 0.05). The total search volumes for SOM, rhinosinusitis, NPC, and AH decreased in 2020 compared to 2019. Discussion: SOM exhibited a discernible epidemiological connection with rhinosinusitis, nasal septal deviation (NSD), tonsillitis, pharyngolaryngitis, and nasopharyngeal carcinoma (NPC). A decrease in public gatherings was observed to effectively reduce the incidences of SOM. This underscores the pivotal role of social measures in influencing the prevalence of SOM and emphasizes the intricate interplay between SOM and various associated health factors, with implications for public health strategies.


Assuntos
Refluxo Gastroesofágico , Neoplasias Nasofaríngeas , Otite Média com Derrame , Faringite , Rinite Alérgica , 60523 , Tonsilite , Humanos , Otite Média com Derrame/epidemiologia , Pandemias , Carcinoma Nasofaríngeo/complicações , Rinite Alérgica/complicações , Hipertrofia/complicações , Faringite/complicações , Tonsilite/complicações , Refluxo Gastroesofágico/complicações , Neoplasias Nasofaríngeas/complicações
18.
Blood Press ; 33(1): 2326298, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38469724

RESUMO

OBJECTIVE: The aim of this study was to describe and compare echocardiographic findings before renal sympathetic denervation (RDN) and 6 and 24 months after the procedure. MATERIALS AND METHODS: Patients with treatment resistant hypertension (TRH) were included in this non-randomised intervention study. RDN was performed by a single experienced operator using the Symplicity Catheter System. Echocardiographic measurements were performed at baseline, and after 6 and 24 months. RESULTS: The cohort consisted of 21 patients with TRH, with a mean systolic office blood pressure (BP) of 163 mmHg and mean diastolic BP 109 mmHg. Mixed model analysis showed no significant change in left ventricular (LV) mass index (LVMI) or left atrium volume index (LAVI) after the RDN procedure. Higher LVMI at baseline was significantly associated with greater reduction in LVMI (p < 0.001). Relative wall thickness (RWT) increased over time (0.48 mm after two years) regardless of change in BP. There was a small but significant reduction in LV end-diastolic (LVIDd) and end-systolic (LVIDs) diameters after RDN, with a mean reduction of 2.6 and 2.4 mm, respectively, after two years. Progression to concentric hypertrophy was observed only in in patients who did not achieve normal BP values, despite BP reduction after RDN. CONCLUSION: There was no reduction of LV mass after RDN. We found a small statistically significant reduction in LVIDd and LVIDs, which together with increase in RWT can indicate progression towards concentric hypertrophy. BP reduction after RDN on its own does not reverse concentric remodelling if target BP is not achieved.


Assuntos
Hipertensão , Humanos , Resultado do Tratamento , Pressão Sanguínea/fisiologia , Simpatectomia/métodos , Ecocardiografia , Hipertrofia/complicações , Rim/diagnóstico por imagem , Rim/cirurgia
19.
Int J Mol Sci ; 25(5)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38474216

RESUMO

Excessive lipid accumulation in adipocytes is a primary contributor to the development of metabolic disorders, including obesity. The consumption of bioactive compounds derived from natural sources has been recognized as being safe and effective in preventing and alleviating obesity. Therefore, we aimed to explore the antilipidemic effects of pennogenin 3-O-ß-chacotrioside (P3C), a steroid glycoside, on hypertrophied 3T3-L1 adipocytes. Oil Red O and Nile red staining demonstrated a P3C-induced reduction in lipid droplet accumulation. Additionally, the increased expression of adipogenic and lipogenic factors, including PPARγ and C/EBPα, during the differentiation process was significantly decreased by P3C treatment at both the protein and mRNA levels. Furthermore, P3C treatment upregulated the expression of fatty acid oxidation-related genes such as PGC1α and CPT1a. Moreover, mitochondrial respiration and ATP generation increased following P3C treatment, as determined using the Seahorse XF analyzer. P3C treatment also increased the protein expression of mitochondrial oxidative phosphorylation in hypertrophied adipocytes. Our findings suggest that P3C could serve as a natural lipid-lowering agent, reducing lipogenesis and enhancing mitochondrial oxidative capacity. Therefore, P3C may be a promising candidate as a therapeutic agent for obesity-related diseases.


Assuntos
Adipogenia , Metabolismo dos Lipídeos , Camundongos , Animais , Adipogenia/genética , Obesidade/metabolismo , Hipertrofia , Lipídeos/farmacologia , Estresse Oxidativo , Células 3T3-L1 , PPAR gama/metabolismo
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