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1.
Nutrients ; 16(17)2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39275318

RESUMO

Studies have demonstrated the therapeutic effects of Lindera plants. This study was undertaken to reveal the antihypertensive properties of Lindera erythrocarpa leaf ethanolic extract (LEL). Aorta segments of Sprague-Dawley rats were used to study the vasodilatory effect of LEL, and the mechanisms involved were evaluated by treating specific inhibitors or activators that affect the contractility of blood vessels. Our results revealed that LEL promotes a vasorelaxant effect through the nitric oxide/cyclic guanosine 3',5'-monophosphate pathway, blocking the Ca2+ channels, opening the K+ channels, and inhibiting the vasoconstrictive action of angiotensin II. In addition, the effects of LEL on blood pressure were investigated in spontaneously hypertensive rats by the tail-cuff method. LEL (300 or 1000 mg/kg) was orally administered to the rats, and 1000 mg/kg of LEL significantly lowered the blood pressure. Systolic blood pressure decreased by -20.06 ± 4.87%, and diastolic blood pressure also lowered by -30.58 ± 5.92% at 4 h in the 1000 mg/kg LEL group. Overall, our results suggest that LEL may be useful to treat hypertensive diseases, considering its vasorelaxing and hypotensive effects.


Assuntos
Anti-Hipertensivos , Pressão Sanguínea , GMP Cíclico , Hipertensão , Lindera , Óxido Nítrico , Extratos Vegetais , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Animais , Anti-Hipertensivos/farmacologia , Extratos Vegetais/farmacologia , Óxido Nítrico/metabolismo , Pressão Sanguínea/efeitos dos fármacos , GMP Cíclico/metabolismo , Masculino , Hipertensão/tratamento farmacológico , Ratos , Lindera/química , Canais de Potássio/metabolismo , Canais de Potássio/efeitos dos fármacos , Canais de Cálcio/metabolismo , Canais de Cálcio/efeitos dos fármacos , Folhas de Planta/química , Vasodilatação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Vasodilatadores/farmacologia
2.
Int J Mol Sci ; 25(17)2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39273182

RESUMO

Elevated metastasis-associated in colon cancer 1 (MACC1) expression in colorectal cancer patients, and high transmembrane 4 L6 family member 5 (TM4SF5) protein expressed on various solid tumors' surface, are linked to aggressive cancer behavior and progression. In this study, adipose-derived stem cells (ASCs) were engineered to produce exosomes (Ex) that target the TM4SF5 protein on tumors. Moreover, MACC1-targeting microRNA was encapsulated within the Ex, resulting in TM4SF5-targeting Ex (MACC1-suppressing miRNA; miR-143). The anticancer effects of these Ex were investigated in vitro using the human colorectal cell line HCT116 and in vivo using colorectal cancer mouse xenograft models. In the in vivo assessment, administration of TM4SF5-targeting Ex[miR-143], referred to as tEx[miR-143] herein, resulted in the smallest tumor size, the lowest tumor growth rate, and the lightest excised tumors compared to other treatments (p < 0.05). It also led to the decreased expression of MACC-1 and anti-apoptotic markers MCL-1 and Bcl-xL while inducing the highest expression of pro-apoptotic markers BAX and BIM. These results were consistent with in vitro findings, where t Ex[miR-143] demonstrated the highest inhibition of HCT116 cell migration and invasion. These findings highlight the potential of tEx[miR-143] as an effective therapeutic strategy for colorectal cancer, demonstrating promising results in both targetability and anti-tumor effects in vitro and in vivo, warranting further investigation in clinical settings.


Assuntos
Neoplasias Colorretais , Exossomos , MicroRNAs , Animais , Humanos , MicroRNAs/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/terapia , Exossomos/metabolismo , Exossomos/genética , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto , Transativadores/genética , Transativadores/metabolismo , Células HCT116 , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Regulação Neoplásica da Expressão Gênica , Modelos Animais de Doenças , Linhagem Celular Tumoral , Apoptose , Camundongos Nus
3.
Medicine (Baltimore) ; 103(22): e38284, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-39259107

RESUMO

Sarcopenia is a contributing factor in the development of long-COVID syndrome. We aimed to investigate how intercostal muscle mass changes over 3 months compared to other chest wall muscles following COVID-19 infection, along with identifying factors contributing to intercostal muscle loss during follow-up. We retrospectively studied 110 COVID-19 patients, analyzing muscle masses in the intercostal, pectoralis, and thoracic 12th vertebra level (T12) on initial and follow-up CT scans. Muscle mass was quantitatively assessed using density histogram analysis. We calculated the muscle difference ratio (MDR) as the following formula: (initial muscle mass - follow-up muscle mass)/initial muscle mass. Patients were categorized into 2 groups: <3 months follow-up (n = 53) and ≥ 3 months follow-up (n = 57). We employed stepwise logistic regression, using intercostal MDR ≥ 25% in follow-up as an independent variable and age < 65 years, ventilator use, steroid use, follow-up > 3 months, hospital stay > 13 days, body mass index < 18.5 kg/m², and female gender as dependent variables. The loss of intercostal muscle was the most severe among the 3 chest wall muscles in the CT follow-up. Intercostal MDR was significantly higher in the ≥ 3 months follow-up group compared to the < 3 months group (32.5 ±â€…23.6% vs 19.0 ±â€…21.1%, P = .002). There were no significant differences in pectoralis MDR or T12 MDR between the 2 groups. Stepwise logistic regression identified steroid use (3.494 (1.419-8.604), P = .007) and a follow-up period > 3 months [3.006 (1.339-6.748), P = .008] as predictors of intercostal MDR ≥ 25%. The intercostal muscle wasting was profound compared to that in the pectoralis and T12 skeletal muscles in a follow-up CT scan, and the intercostal muscle wasting was further aggravated after 3 months of COVID-19 infection. The use of steroids and a follow-up period exceeding 3 months were significant predictors for ≥ 25% of intercostal muscle wasting in follow-up.


Assuntos
COVID-19 , Músculos Intercostais , Sarcopenia , Centros de Atenção Terciária , Tomografia Computadorizada por Raios X , Humanos , COVID-19/complicações , COVID-19/diagnóstico por imagem , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Músculos Intercostais/diagnóstico por imagem , Sarcopenia/diagnóstico por imagem , Sarcopenia/epidemiologia , Sarcopenia/etiologia , Idoso , SARS-CoV-2 , Adulto
4.
Sensors (Basel) ; 24(15)2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39123811

RESUMO

This paper proposes a scheme for predicting ground reaction force (GRF) and center of pressure (CoP) using low-cost FSR sensors. GRF and CoP data are commonly collected from smart insoles to analyze the wearer's gait and diagnose balance issues. This approach can be utilized to improve a user's rehabilitation process and enable customized treatment plans for patients with specific diseases, making it a useful technology in many fields. However, the conventional measuring equipment for directly monitoring GRF and CoP values, such as F-Scan, is expensive, posing a challenge to commercialization in the industry. To solve this problem, this paper proposes a technology to predict relevant indicators using only low-cost Force Sensing Resistor (FSR) sensors instead of expensive equipment. In this study, data were collected from subjects simultaneously wearing a low-cost FSR Sensor and an F-Scan device, and the relationship between the collected data sets was analyzed using supervised learning techniques. Using the proposed technique, an artificial neural network was constructed that can derive a predicted value close to the actual F-Scan values using only the data from the FSR Sensor. In this process, GRF and CoP were calculated using six virtual forces instead of the pressure value of the entire sole. It was verified through various simulations that it is possible to achieve an improved prediction accuracy of more than 30% when using the proposed technique compared to conventional prediction techniques.


Assuntos
Redes Neurais de Computação , Pressão , Humanos , Marcha/fisiologia , Calibragem , Sapatos , Masculino , Algoritmos
5.
Int J Mol Sci ; 25(15)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39125672

RESUMO

Torilis japonica (TJ) fruit, is a herb that is traditionally used for erectile dysfunction (ED). Given the shared mechanisms of ED and hypertension through vascular smooth muscle, we hypothesized that TJ would be effective in vasodilation and blood pressure reduction. This study confirmed the authenticity of TJ samples via DNA barcoding and quantified the main active compound, torilin, using HPLC. TJ was extracted with distilled water (TJW) and 50% ethanol (TJE), yielding torilin contents of 0.35 ± 0.01% and 2.84 ± 0.02%, respectively. Ex vivo tests on thoracic aortic rings from Sprague-Dawley rats showed that TJE (3-300 µg/mL) induced endothelium-independent, concentration-dependent vasodilation, unlike TJW. Torilin caused concentration-dependent relaxation with an EC50 of 210 ± 1.07 µM. TJE's effects were blocked by a voltage-dependent K+ channel blocker and alleviated contractions induced by CaCl2 and angiotensin II. TJE inhibited vascular contraction induced by phenylephrine or KCl via extracellular CaCl2 and enhanced inhibition with nifedipine, indicating involvement of voltage-dependent and receptor-operated Ca2+ channels. Oral administration of TJE (1000 mg/kg) significantly reduced blood pressure in spontaneously hypertensive rats. These findings suggest TJ extract's potential for hypertension treatment through vasorelaxant mechanisms, though further research is needed to confirm its efficacy and safety.


Assuntos
Pressão Sanguínea , Endotélio Vascular , Frutas , Extratos Vegetais , Ratos Sprague-Dawley , Vasodilatação , Animais , Ratos , Vasodilatação/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Masculino , Frutas/química , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Anti-Hipertensivos/farmacologia , Vasodilatadores/farmacologia , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Ratos Endogâmicos SHR , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Hipertensão/fisiopatologia
6.
Pediatr Int ; 66(1): e15786, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39161233

RESUMO

BACKGROUND: Pediatric inflammatory bowel disease (PIBD) affects different age groups and its incidence is increasing worldwide. However, there is a lack of research focusing on age subgroups in Asian countries. In this nationwide population-based study, we investigated the epidemiology of PIBD among different age subgroups in Korea. METHODS: We analyzed Korean health administration data from 2005 to 2016. Data were divided by age at diagnosis as follows: group 1, 0-1 years; group 2, 2-5 years; group 3, 6-9 years; group 4, 10-16 years. We analyzed the overall incidence, temporal changes, and regional differences by age subgroups, using Poisson regression analysis. RESULTS: From 2005 to 2016, 2734 inflammatory bowel disease (IBD) cases were diagnosed among patients under 17 years of age. In the overall population, the incidence rate of PIBD over the entire study period was 2.248/105 person-years (PY), significantly increasing from 1.173/105 PY in 2005-2007 to 3.267/105 PY in 2014-2016. The incidence rates in groups 1 and 2 remained unchanged, whereas those of groups 3 and 4 increased significantly. The same trend was observed when analyzed separately for Crohn's disease (CD) and ulcerative colitis (UC). The incidence rates of CD in groups 3 and 4 showed differences between metropolitan and non-metropolitan areas, whereas those in groups 1 and 2, and UC of all age subgroups showed no difference. CONCLUSIONS: The temporal trend and regional differences of PIBD differed among age subgroups, suggesting that genetic and environmental factors have varying impacts on IBD development across different subgroups.


Assuntos
Doenças Inflamatórias Intestinais , Humanos , República da Coreia/epidemiologia , Criança , Adolescente , Incidência , Masculino , Feminino , Pré-Escolar , Lactente , Recém-Nascido , Doenças Inflamatórias Intestinais/epidemiologia , Distribuição por Idade , Doença de Crohn/epidemiologia , Colite Ulcerativa/epidemiologia
7.
J Am Chem Soc ; 146(33): 23230-23239, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39116214

RESUMO

TMEM175 is a lysosomal potassium and proton channel that is associated with the development of Parkinson's disease. Advances in understanding the physiological roles of TMEM175 have been hampered by the absence of selective inhibitors, and studies involving genetic perturbations have yielded conflicting results. Here, we report the discovery and characterization of the first reported TMEM175-selective inhibitors, 2-phenylpyridin-4-ylamine (2-PPA), and AP-6. Cryo-EM structures of human TMEM175 bound by 2-PPA and AP-6 reveal that they act as pore blockers, binding at distinct sites in the pore and occluding the ion permeation pathway. Acute inhibition of TMEM175 by 2-PPA or AP-6 increases the level of lysosomal macromolecule catabolism, thereby accelerating macropinocytosis and other digestive processes. These inhibitors may serve as valuable tools to study the roles of TMEM175 in regulating lysosomal function and provide useful templates for future therapeutic development in Parkinson's disease.


Assuntos
Lisossomos , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Lisossomos/metabolismo , Descoberta de Drogas , Canais Iônicos/antagonistas & inibidores , Canais Iônicos/metabolismo , Canais Iônicos/química , Piridinas/química , Piridinas/farmacologia , Modelos Moleculares , Microscopia Crioeletrônica , Canais de Potássio
8.
Int J Mol Sci ; 25(14)2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39063203

RESUMO

Previous studies have revealed the medicinal and therapeutic effects of Galla chinensis. However, no studies have focused on the antihypertensive effects of G. chinensis. Therefore, we aimed to determine the vasorelaxant and hypotensive effects of G. chinensis 50% ethanolic extract (GCE). To evaluate the vascular relaxing effect of GCE, experiments were conducted using aortic segments dissected from Sprague Dawley rats. GCE showed a vasorelaxant effect via the nitric oxide/cyclic guanosine 3',5'-monophosphate pathway, inhibiting Ca2+ channels, and activating K+ channels. The hypotensive effects of GCE were evaluated in spontaneously hypertensive rats (SHRs). The SHRs were randomly divided into a control group and orally administered GCE group (100 or 300 mg/kg). The systolic and diastolic blood pressure decreased significantly by -19.47 ± 4.58% and -31.14 ± 7.66% in the GCE 100 mg/kg group, and -21.64 ± 2.40% and -31.91 ± 5.75% in the GCE 300 mg/kg group at 4 h after administration. Considering its vasorelaxant and hypotensive effects, our results indicate that GCE may be a valuable solution for the control of hypertension. However, further studies on the long-term administration and toxicity of GCE are required.


Assuntos
Anti-Hipertensivos , Pressão Sanguínea , Extratos Vegetais , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Vasodilatadores , Animais , Vasodilatadores/farmacologia , Ratos , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Masculino , Extratos Vegetais/farmacologia , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Óxido Nítrico/metabolismo , Vasodilatação/efeitos dos fármacos , GMP Cíclico/metabolismo , Aorta/efeitos dos fármacos , Medicamentos de Ervas Chinesas , Taninos
10.
Ann Surg Treat Res ; 106(6): 354-360, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38868585

RESUMO

Purpose: Numerous efforts have been made to achieve minimally invasive surgery, such as single-port laparoscopic surgery. However, few studies have provided long-term follow-up information, and the number of patients with hepatocellular carcinoma (HCC) in previous studies has been small. The purpose in this study is to compare the long-term oncological outcomes of HCC patients who underwent single-port laparoscopic hepatectomy (SPLH) with those of patients who underwent multiport laparoscopic hepatectomy (MPLH). Methods: We retrospectively reviewed the medical records of 135 patients with HCC who underwent laparoscopic liver between January 2008 and December 2018. Of the 135 patients, 53 underwent MPLH, and 82 underwent SPLH. Results: From January 2008 to December 2018, 135 patients underwent laparoscopic hepatectomy for HCC. Among them, 82 patients underwent SPLH, and 53 patients underwent MPLH. Neither long-term overall survival (P = 0.849) nor recurrence-free survival (P = 0.057) differed significantly between the 2 groups, even though the recurrence rate was higher in the SPLH group. In the univariable analysis of risk factors for recurrence, multiple tumors, SPLH method, and portal vein invasion were statistically significant (P < 0.05). Multivariable analysis showed that the SPLH method and portal vein invasion were independent adverse prognostic factors for recurrence-free survival. Conclusion: In terms of both short-term and long-term outcomes, the SPLH method seems to be a feasible approach for HCC in select patients. Because the potential risk of margin recurrence might produce poor oncological outcomes, strict patient selection is essential to ensure that an adequate safety margin can be secured.

12.
Imaging Sci Dent ; 54(1): 115-120, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38571774

RESUMO

Components derived from an infected lesion within the bone can spread through various passages in the mandible, particularly via the mental foramen. Radiologically, the spread of infection is typically nonspecific and challenging to characterize; however, multislice computed tomography (MSCT) can effectively detect pathological changes in soft tissues and the bone marrow space. This report describes the case of a 55-year-old woman who experienced mental nerve paresthesia due to a periapical infection of the right mandibular second premolar. MSCT imaging revealed increased attenuation around the periapical lesion extending into the mandibular canal and loss of the juxtamental foraminal fat pad. Following endodontic treatment of the tooth suspected to be the source of the infection, the patient's symptoms resolved, and the previous MSCT imaging findings were no longer present. Increased bone marrow attenuation and obliteration of the fat plane in the buccal aspect of the mental foramen may serve as radiologic indicators of inflammation spreading from the bone marrow space.

13.
Int J Mol Sci ; 25(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38673809

RESUMO

Cnidium monnieri (L.) Cusson, a member of the Apiaceae family, is rich in coumarins, such as imperatorin and osthole. Cnidium monnieri fruit (CM) has a broad range of therapeutic potential that can be used in anti-bacterial, anti-cancer, and sexual dysfunction treatments. However, its efficacy in lowering blood pressure through vasodilation remains unknown. This study aimed to assess the potential therapeutic effect of CM 50% ethanol extract (CME) on hypertension and the mechanism of its vasorelaxant effect. CME (1-30 µg/mL) showed a concentration-dependent vasorelaxation on constricted aortic rings in Sprague Dawley rats induced by phenylephrine via an endothelium-independent mechanism. The vasorelaxant effect of CME was inhibited by blockers of voltage-dependent and Ca2+-activated K+ channels. Additionally, CME inhibited the vascular contraction induced by angiotensin II and CaCl2. The main active compounds of CM, i.e., imperatorin (3-300 µM) and osthole (1-100 µM), showed a concentration-dependent vasorelaxation effect, with half-maximal effective concentration values of 9.14 ± 0.06 and 5.98 ± 0.06 µM, respectively. Orally administered CME significantly reduced the blood pressure of spontaneously hypertensive rats. Our research shows that CME is a promising treatment option for hypertension. However, further studies are required to fully elucidate its therapeutic potential.


Assuntos
Anti-Hipertensivos , Pressão Sanguínea , Cnidium , Etanol , Frutas , Furocumarinas , Hipertensão , Extratos Vegetais , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Vasodilatadores , Animais , Cnidium/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Pressão Sanguínea/efeitos dos fármacos , Ratos , Frutas/química , Vasodilatadores/farmacologia , Masculino , Anti-Hipertensivos/farmacologia , Etanol/química , Furocumarinas/farmacologia , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Vasodilatação/efeitos dos fármacos , Cumarínicos/farmacologia , Cumarínicos/química
14.
Foods ; 13(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38611347

RESUMO

Hypertension is the crucial modifiable risk factor for cardiovascular diseases, and efforts to identify functional foods that are effective for hypertension control are increasing. The nutgall tree (NT, Rhus chinensis Mill.) is used in traditional medicine and food because of its medicinal value. However, the role of NT in hypertension has not been investigated. Therefore, the hypotensive effect of NT leaf ethanol extract (NTE) was investigated in spontaneously hypertensive rats (SHRs). SHRs were allocated to three groups (control, 300, or 1000 mg/kg NTE), and blood pressure was measured before and after oral administration. Systolic and diastolic blood pressure significantly decreased in the NTE 1000 mg/kg group and was the lowest at 2 h after administration (-26.4 ± 10.3, -33.5 ± 9.8%, respectively). Daily NTE administration for five days also resulted in a similar effect. Further, the vasorelaxant effects and related mechanisms were investigated in the aortas of Sprague Dawley rats. NTE showed the dose-dependent blood-vessel-relaxing effect, and its mechanism involves the NO-sGC-cGMP pathway, activation of K+ channels, and reduction in the vasoconstrictive action of angiotensin II. Therefore, our study provides basic data indicating the potential use of NTE as a functional food for high blood pressure.

15.
Animals (Basel) ; 14(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38612332

RESUMO

Sinus venosus atrial septal defects (SVASDs), concurrent with partial anomalous pulmonary venous connections (PAPVCs), are a rare congenital heart disease in dogs. Surgical correction is essential when clinical signs or significant hemodynamic changes are present. We aimed to report on the successful surgical correction of an SVASD with PAPVCs, using a computed tomography (CT)-based customized 3D cardiac model. A 10-month-old male poodle was referred for corrective surgery for an ASD. Echocardiography confirmed a hemodynamically significant left-to-right shunting flow through an interatrial septal defect and severe right-sided heart volume overload. For a comprehensive diagnosis, a CT scan was performed, which confirmed an SVASD with PAPVCs. A customized 3D cardiac model was used for preoperative decision-making and surgical rehearsal. The defect was repaired using an autologous pericardial patch under a cardiopulmonary bypass (CPB). Temporary pacing was applied for sinus bradycardia and third-degree atrioventricular block. The patient recovered from the anesthesia without further complications. The pacemaker was removed during hospitalization and the patient was discharged without complications 2 weeks post-surgery. At the three-month follow-up, there was no shunting flow in the interatrial septum and the right-sided volume overload had been resolved. The cardiac medications were discontinued, and there were no complications. This report indicates the validity of surgical correction under CPB for an SVASD with PAPVCs, and the advantages of utilizing a CT-based 3D cardiac model for preoperative planning to increase the surgical success rate.

16.
J Biomed Sci ; 31(1): 38, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38627765

RESUMO

BACKGROUND: Mitochondria are essential organelles involved in cellular energy production. Changes in mitochondrial function can lead to dysfunction and cell death in aging and age-related disorders. Recent research suggests that mitochondrial dysfunction is closely linked to neurodegenerative diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonist has gained interest as a potential treatment for Parkinson's disease (PD). However, the exact mechanisms responsible for the therapeutic effects of GLP-1R-related agonists are not yet fully understood. METHODS: In this study, we explores the effects of early treatment with PT320, a sustained release formulation of the GLP-1R agonist Exenatide, on mitochondrial functions and morphology in a progressive PD mouse model, the MitoPark (MP) mouse. RESULTS: Our findings demonstrate that administration of a clinically translatable dose of PT320 ameliorates the reduction in tyrosine hydroxylase expression, lowers reactive oxygen species (ROS) levels, and inhibits mitochondrial cytochrome c release during nigrostriatal dopaminergic denervation in MP mice. PT320 treatment significantly preserved mitochondrial function and morphology but did not influence the reduction in mitochondria numbers during PD progression in MP mice. Genetic analysis indicated that the cytoprotective effect of PT320 is attributed to a reduction in the expression of mitochondrial fission protein 1 (Fis1) and an increase in the expression of optic atrophy type 1 (Opa1), which is known to play a role in maintaining mitochondrial homeostasis and decreasing cytochrome c release through remodeling of the cristae. CONCLUSION: Our findings suggest that the early administration of PT320 shows potential as a neuroprotective treatment for PD, as it can preserve mitochondrial function. Through enhancing mitochondrial health by regulating Opa1 and Fis1, PT320 presents a new neuroprotective therapy in PD.


Assuntos
Citocromos c , Exenatida , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Doenças Mitocondriais , Citocromos c/uso terapêutico , Doenças Mitocondriais/tratamento farmacológico , Doenças Mitocondriais/metabolismo , Exenatida/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Modelos Animais de Doenças
17.
Ital J Pediatr ; 50(1): 58, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561824

RESUMO

BACKGROUND: Several studies have identified graded oxygen saturation targets to prevent retinopathy of prematurity (ROP), a serious complication in preterm infants. We aimed to analyze the critical period of oxygen supplementation and/or invasive ventilation associated with severe ROP. METHODS: This retrospective case-control study included neonates with a gestational age (GA) < 29 weeks. Participants were divided into two groups: treated retinopathy and untreated/no retinopathy. Time-weighted average FiO2 (TWAFiO2) and weekly invasive ventilation were compared between groups by postnatal age (PNA) and postmenstrual age (PMA). The association of treated retinopathy with TWAFiO2 and invasive ventilation was analyzed. RESULTS: Data from 287 neonates were analyzed; 98 were treated for ROP and had lower GAs (25.5 vs. 27.4 weeks, p < 0.01) and lower birthweights (747.6 vs. 1014 g, p < 0.001) than those with untreated/no ROP. TWAFiO2 was higher from PMA 26-34 weeks, except for PMA 31 weeks in treated ROP, and higher in the first nine weeks of life in treated ROP. On multiple logistic regression, TWAFiO2 and invasive ventilation were associated with ROP treatment during the first seven weeks PNA. Invasive ventilation was associated with ROP treatment from PMA 26-31 weeks; no association was found for TWAFiO2 and PMA. CONCLUSIONS: Amount of oxygen supplementation and/or invasive ventilation during the first 7 weeks of life or up to 31 weeks PMA was associated with development of severe ROP. This period might be candidate timing for strict oxygen supplementation strategies in preterm infants, while concerns of mortality with low oxygen supplementation should be further explored.


Assuntos
Ventilação não Invasiva , Retinopatia da Prematuridade , Lactente , Recém-Nascido , Humanos , Retinopatia da Prematuridade/prevenção & controle , Recém-Nascido Prematuro , Oxigênio/uso terapêutico , Estudos Retrospectivos , Estudos de Casos e Controles , Idade Gestacional , Oxigenoterapia/efeitos adversos , Fatores de Risco
18.
ACS Appl Mater Interfaces ; 16(13): 16328-16339, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38516946

RESUMO

Kesterite-based Cu2ZnSn(S,Se)4 (CZTSSe) thin-film solar cells (TFSCs) are a promising candidate for low-cost, clean energy production owing to their environmental friendliness and the earth-abundant nature of their constituents. However, the advancement of kesterite TFSCs has been impeded by abundant defects and poor microstructure, limiting their performance potential. In this study, we present efficient Ag-alloyed CZTSSe TFSCs enabled by a facile metallic precursor engineering approach. The positioning of the Ag nanolayer in the metallic stacked precursor proves crucial in expediting the formation of Cu-Sn metal alloys during the alloying process. Specifically, Ag-included metallic precursors promote the growth of larger grains and a denser microstructure in CZTSSe thin films compared to those without Ag. Moreover, the improved uniformity of Ag, facilitated by the evaporation deposition technique, significantly suppresses the formation of detrimental defects and related defect clusters. This suppression effectively reduces nonradiative recombination, resulting in enhanced performance in kesterite TFSCs. This study not only introduces a metallic precursor engineering strategy for efficient kesterite-based TFSCs but also accelerates the development of microstructure evolution from metallic stacked precursors to metal chalcogenide compounds.

19.
Ann Surg Treat Res ; 106(3): 155-168, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38435492

RESUMO

Purpose: Liver fibrosis is a critical health issue with limited treatment options. This study investigates the potential of PGC-Sec, a secretome derived from peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-overexpressing adipose-derived stem cells (ASCs), as a novel therapeutic strategy for liver fibrosis. Methods: Upon achieving a cellular confluence of 70%-80%, ASCs were transfected with pcDNA-PGC-1α. PGC-Sec, obtained through concentration of conditioned media using ultrafiltration units with a 3-kDa cutoff, was assessed through in vitro assays and in vitro mouse models. Results: In vitro, PGC-Sec significantly reduced LX2 human hepatic stellate cell proliferation and mitigated mitochondrial oxidative stress compared to the control-secretome. In an in vivo mouse model, PGC-Sec treatment led to notable reductions in hepatic enzyme activity, serum proinflammatory cytokine concentrations, and fibrosis-related marker expression. Histological analysis demonstrated improved liver histology and reduced fibrosis severity in PGC-Sec-treated mice. Immunohistochemical staining confirmed enhanced expression of PGC-1α, optic atrophy 1 (a mitochondrial function marker), and peroxisome proliferator-activated receptor alpha (an antifibrogenic marker) in the PGC-Sec-treated group, along with reduced collagen type 1A expression (a profibrogenic marker). Conclusion: These findings highlight the therapeutic potential of PGC-Sec in combating liver fibrosis by enhancing mitochondrial biogenesis and function, and promoting antifibrotic processes. PGC-Sec holds promise as a novel treatment strategy for liver fibrosis.

20.
Medicina (Kaunas) ; 60(3)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38541143

RESUMO

Background and Objectives: Peripherally inserted central catheter (PICC) placement plays an important role in clinical practice. This study aimed to provide an equation for the proper estimation of catheter length in cases of PICC placement without imaging guidance in relation to patient height, weight, sex, and age. Materials and Methods: For 1137 PICC placement cases in both arm veins of 954 patients at a single center, the elbow crease to the cavoatrial junction length (ECL) was calculated as follows: ECL = (PICC length) + (distance from the elbow crease to the puncture site). We analyzed the relationship between ECL and patient characteristics and suggested a new equation for ECL based on height, weight, sex, and age. Results: The average ECL was 48.0 ± 2.4 cm in the right side and 51.0 ± 3.0 cm in the left side. ECL in the right arm was significantly correlated with patient height, sex, and age, whereas the ECL in the left arm was additionally significantly correlated with patient weight. The ECL (cm) prediction model was as follows: right ECL = 26.32 + 1.33 × (female = 1, male = 2) - 0.02 × age (years) + 0.13 × height (cm); left ECL = 22.09 + 1.28 × (female = 1, male = 2) + 0.02 × age (years) + 0.14 × height (cm) + 0.042 × weight (kg). Conclusions: The appropriate PICC length was predicted based on the patient's height, weight, sex, and age. The equations in our study can help predict the optimal catheter length and can be automatically calculated using computerized patient information for bedside procedures in PICC.


Assuntos
Cateterismo Venoso Central , Cateterismo Periférico , Humanos , Masculino , Feminino , Cateterismo Venoso Central/métodos , Cateterismo Periférico/métodos , Catéteres , Estudos Retrospectivos
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