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1.
Histol Histopathol ; : 18470, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35553404

RESUMO

Melanocytes have a complex function and play an important role in a variety of regulatory mechanisms in the human system. Melanocyte stem cells (MelSCs) serve as a reservoir to replenish the melanocytes by regenerating new ones, and they are capable of self-renewal and differentiation to maintain their homeostasis, repair, and regeneration in tissues. The numerical decrease and functional impairment of MelSCs may be closely related to the development and treatment response of many skin diseases. However, the current knowledge about MelSCs mainly comes from studies in mice, and little is known about human MelSC markers; especially, their markers are still unclear or lack consensus. This leads to uncertainty in clinical findings, which further limits our comprehensive understanding of pigmentary disorders and also hinders the progress of new treatments. Thus, in this review article, combined with our previous and current work, we summarize and update the recent advances in MelSC research, including the molecular markers of human MelSCs and their niche, as well as the association of MelSCs with skin diseases, including vitiligo, hair greying, and melanoma. Due to the limited tools available to explore the identified characteristics of human MelSCs, pluripotent stem cells can provide a new research model for further study, especially combined with CRISPR/Cas9 technology. The visualization of human MelSCs' development and differentiation can help to identify their molecular characteristics and understand their cellular fate dynamically, which will allow us not only to further explore their roles in associated diseases, but also to achieve MelSC-based cellular therapy.

2.
J Clin Neurosci ; 101: 37-46, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35526362

RESUMO

PURPOSE: Solitary type primary intracranial malignant melanoma (PIMM) is extremely rare but fatal. The optimal treatment algorithm according to clinical relevance of symptoms and outcomes is unclear. This series emphasized the prognostic factors of solitary PIMM and established the treatment algorithm for this rare disease. METHODS: Patients with solitary PIMMs were pathologically verified and treated with neurosurgical tumor resection. All solitary PIMMs recruited at our institute received multidisciplinary team care. We analyzed the clinical findings and prognostic factors. RESULTS: The study cohort included 10 patients. PIMMs in solitary type impacted middle-aged populations with male predominance in Taiwan. Most patients (80%) presented a single tumor initially. Six patients had progressed to multiplicity after the initial treatment. Rates of tumor bleeding and leptomeningeal metastasis seeding (LS) are high in solitary PIMMs. Patients who had gross-total resection (GTR) had better survival than those who had incomplete resection, with median overall survival (OS) rates of 170.4 months vs. 5.23 months (p = 0.004). Multiplicity, eloquent area involvement, initial tumor bleeding, LS, hydrocephalus, and Karnofsky Performance Score < 80 at diagnosis were associated with negative outcomes in progression-free survival and OS. Adjuvant radiotherapy for patients who had LS and for those who cannot undergo grossly total tumor removal resulted in a good outcome. CONCLUSIONS: GTR demonstrated better outcomes for solitary PIMM. For recurrent tumors, aggressively repeated surgical resection remained beneficial for selected cases. Adjuvant radiotherapy was a treatment option for LS following operation. We proposed a possible treatment algorithm for solitary PIMM.

3.
J Colloid Interface Sci ; 622: 675-689, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35533482

RESUMO

Polymeric carbon nitride (CN) has evoked considerable attention in photocatalysis, however, its π-deficiency conjugated frameworks engendering weak visible-light absorption and rapid charge recombination hinder the practical utilizations. Herein, a novel donor-acceptor (D-A) conjugated polymer based on triptycene incorporated carbon nitride (T-CN) has been facilely prepared by thermal copolymerization of melamine and 2,6,14-triaminotriptycene. Combined with the density functional theory (DFT) calculations, it is found that the formation of intramolecular charge transfer and the extended π-conjugative effect in the D-A structure contribute to a broadened light-harvesting spectral range, a higher charge separation/transfer efficiency and more active sites of T-CN for photoredox reactions. The T-CN catalyst accomplished superior visible-light photocatalytic performance in both hydrogen evolving and carbon dioxide reduction. The optimal T-CN catalyst exhibited the highest hydrogen evolution rate of 80.9 ± 1.3 µmol·h-1 and carbon monoxide production rate of 8.1 ± 0.2 µmol·h-1, which are ca. 8-fold and 20-fold of bulk CN, respectively. The convenient strategy of constructing D-A conjugated structure opens up a new intriguing avenue toward the rational creation of efficient polymeric nanomaterials for versatile applications of solar fuel production.

4.
J Oncol ; 2022: 3819564, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35498543

RESUMO

Background: Whether more tumor numbers detected in surgery compared to preoperative image affecting survival of colorectal liver metastases (CRLM) patients after hepatectomy combined with microwave ablation (MWA) remains unclear. Methods: From 2013 to 2018, 85 CRLM patients who underwent hepatectomy combined with MWA were retrospectively assessed. Compared to the tumor numbers in preoperative image, patients with equal intraoperative tumor numbers were defined as the equal number group (n = 45); patients detected more tumor numbers in surgery were defined as the more number group (n = 40). Clinicopathological factors and prognosis were compared between two groups. Results: Compared to the equal number group, the more number group was characterized by more lymphatic metastasis, synchronous metastasis of liver lesion, and tumor numbers over 5 (all P < 0.05). Median survival time was 46.7 months and 26.8 months in the equal and more number group. Significantly worse overall survival (OS) was found in more number group to the equal number group (P = 0.027). In Cox analysis, more tumor number than image and high level of carbohydrate antigen 19-9 (CA19-9) were poor prognostic factors for OS. Conclusion: In patients receiving hepatectomy combined with MWA, detecting more liver metastases in surgery than preoperative image indicates poor long-term survival. These patients were characterized by more lymphatic metastasis, synchronous metastasis of liver lesion, and tumor numbers over 5. Intensive follow-up to detect early recurrence and potent postoperative therapy to improve survival may be justified in patients detected more tumor numbers in surgery with a high CA19-9 level.

5.
Biomed Res Int ; 2022: 9873924, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528166

RESUMO

[This corrects the article DOI: 10.1155/2015/263630.].

6.
Histol Histopathol ; : 18458, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35417038

RESUMO

Direct reprogramming, whether in vitro or in vivo, has attracted great attention because of its advantages of convenience, short-term conversion, direct targets, no immune rejection, and potential clinical applications. In addition, due to its independence from the pluripotent state, direct programming minimizes some safety concerns associated with the use of human pluripotent stem cells. However, the significant limitations of reprogrammed cells, such as poor proliferative ability, low efficiency, and immature function, need to be addressed before the clinical application potential can be expanded. Here, we review the recent achievements of direct reprogramming in 2D and 3D systems in vitro and in vivo, covering cells derived from the three germ layers from stem/progenitor cells to terminal cells, such as hepatocytes, pancreatic ß cells, cardiomyocytes, endothelial cells, osteoblasts, chondrocytes, neurons, and melanocytes. Combining our lab experiences with current work, we summarize the practical and potential issues that need to be solved and the prospects of strategies for addressing the current dilemmas. Through comprehensive analyses, it is concluded that the directions for dealing with efficiency and functionality issues could be the optimization of transcription factors, the upgradation for delivery systems, the regulation of epigenetic factors and pathways, and the improvement of cellular maintenance conditions. Besides, converting cells into the progenitor state firstly and then differentiating them into the desired cell types with chemical compounds may provide an approach to obtaining functional and safe converted cells in batches with a better proliferative ability. With the emergence of more and more direct reprogramming techniques and approaches with both safety and effectiveness, it is bound to bring a new dawn for mechanism research and therapeutic applications for relevant diseases in the future.

7.
Front Neurosci ; 16: 824389, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386590

RESUMO

Cochlear implants are the most successful sensory prostheses worldwide, and they can be useful for patients with severe and profound hearing impairment. However, various complications, including infection, pain, and device failure which is mainly due to falls and trauma, are associated with the use of cochlear implants. Reimplantation is required to replace the initial device in severe complications. Nevertheless, reimplantation can present certain surgical risks and may impose a significant economic and psychological burden on patients and their families; therefore, it requires greater attention and focus. This article presents a review of the literature on cochlear reimplantation and summarizes the current status, knowledge gaps, and future research directions on cochlear reimplantation. Since 1980s, cochlear reimplantation techniques can be considered to be relatively mature; however, some clinical and scientific problems remain unresolved, including the lack of a unified definition of cochlear reimplantation, non-standardized calculation of the reimplantation rat, and insufficient effect assessment. This review highlights the urgent need to establish an international consensus statement on cochlear reimplantation research to standardize the definition, calculation formulas of reimplantation rate, and follow-up systems.

8.
Hum Mol Genet ; 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35388883

RESUMO

Wilson's disease (WD) is a copper metabolic disorder caused by a defective ATP7B function. Conventional therapies cause severe side effects and significant variation in efficacy, according to cohort studies. Thus, exploring new therapeutic approaches to prevent progression to liver failure is urgent. To study the physiology and pathology of WD, immortalized cell lines and rodent WD models have been used conventionally; however, a large gap remains among different species as well as in genetic backgrounds among individuals. We generated induced pluripotent stem cells (iPSCs) from 4 WD patients carrying compound heterozygous mutations in the ATP7B gene. ATP7B loss- and gain-of-functions were further manifested with ATP7B-deficient iPSCs and heterozygously corrected R778L WD patient-derived iPSCs using CRISPR-Cas9-based gene editing. Although the expression of ATP7B protein varied among WD-specific hepatocytes differentiated from these iPSCs, the expression and secretion of ceruloplasmin (Cp), a downstream copper carrier in plasma, was consistently decreased in WD-patient-derived and ATP7B-deficient hepatocytes. A transcriptome analysis detected abnormalities in the retinoid signaling pathway and lipid metabolism in WD-specific hepatocytes. Drug screening using WD-patient-derived hepatocytes identified retinoids as promising candidates for rescuing Cp secretion. All-trans retinoic acid (ATRA) also alleviates reactive oxygen species (ROS) production induced by lipid accumulation in WD-specific hepatocytes treated with oleic acid. These patient-derived iPSC-based hepatic models function as effective platforms for the development of potential therapeutics for hepatic steatosis in WD and other fatty liver diseases.

9.
N Biotechnol ; 70: 28-38, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35405333

RESUMO

Acetyl esterases are an important component of the enzymatic machinery fungi use to degrade plant biomass and are classified in several Carbohydrate Esterase families of the CAZy classification system. Carbohydrate Esterase family 16 (CE16) is one of the more recently discovered CAZy families, but only a small number of its enzyme members have been characterized so far, revealing activity on xylan-derived oligosaccharides, as well as activity related to galactoglucomannan. The number of CE16 genes differs significantly in the genomes of filamentous fungi. In this study, four CE16 members were identified in the genome of Aspergillus niger NRRL3 and it was shown that they belong to three of the four phylogenetic Clades of CE16. Significant differences in expression profiles of the genes and substrate specificity of the enzymes were revealed, demonstrating the diversity within this family of enzymes. Detailed characterization of one of these four A. niger enzymes (HaeA) demonstrated activity on oligosaccharides obtained from acetylated glucuronoxylan, galactoglucomannan and xyloglucan, thus establishing this enzyme as a general hemicellulose acetyl esterase. Their broad substrate specificity makes these enzymes highly interesting for biotechnological applications in which deacetylation of polysaccharides is required.

10.
Int J Biochem Cell Biol ; 147: 106212, 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35439649

RESUMO

Loss of muscle mass can lead to diseases such as sarcopenia, diabetes, and obesity, which can worsen the quality of life and increase the incidence of disease. Therefore, understanding the mechanism underlying skeletal muscle differentiation is vital to prevent muscle diseases. We previously found that microRNA-320 (miR-320) is highly expressed in the lean muscle-type pigs, but its regulatory role in myogenesis remains unclear. The bioinformatics prediction indicated that miR-320 could bind to the 3 'untranslated region of growth factor receptor-bound protein-2 (Grb2). We hypothesized that miR-320 targets Grb2 to regulate myoblasts differentiation. To verify this, we transfected miR-320 mimic and inhibitor into C2C12 myoblasts to assess the role of miR-320 during myoblasts differentiation. We used real-time qPCR, luciferase reporter assays, and western blotting to confirm that miR-320 directly targets Grb2 to promote myoblasts differentiation. Moreover, by using a dexamethasone-induced atrophic model of myotubes, we discovered that miR-320 promotes the repair of damaged myotubes. Our findings expand understanding of miRNAs and genes related to regulating skeletal muscle differentiation, and provide insight into underlying therapeutic strategies for muscle diseases.

11.
World J Clin Cases ; 10(6): 1815-1825, 2022 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-35317152

RESUMO

BACKGROUND: Noise-induced hearing loss (NIHL) is the second most common acquired hearing loss following presbycusis. Exposure to recreational noise and minimal use of hearing protection increase the prevalence of NIHL in young females. NIHL is irreversible. Identifying minor hearing pathologies before they progress to hearing problems that affect daily life is crucial. AIM: To compare the advantages and disadvantages of extended high frequency (EHF) and otoacoustic emission and determine an indicator of hearing pathologies at the early sub-clinical stage. METHODS: This cross-sectional study was implemented in West China Hospital of Sichuan University from May to September 2019. A total of 86 participants, aged 18-22 years, were recruited to establish normative thresholds for EHF. Another 159 adults, aged 18-25 years with normal hearing (0.25-8 kHz ≤ 25 dBHL), were allocated to low noise and noise exposure groups. Distortion otoacoustic emission (DPOAE), transient evoked otoacoustic emissions (TEOAE), and EHF were assessed in the two groups to determine the superior technique for detecting early-stage noise-induced pathologies. The chi-square test was used to assess the noise and low noise exposure groups with respect to extended high-frequency audiometry (EHFA), DPOAE, and TEOAE. P ≤ 0.05 was considered statistically significant. RESULTS: A total of 86 participants (66 females and 20 males) aged between 18 and 22 (average: 20.58 ± 1.13) years were recruited to establish normative thresholds for EHF. The normative thresholds for 9, 10, 11.2, 12.5, 14, 16, 18, and 20 kHz were 15, 10, 20, 15, 15, 20, 28, and 0 dBHL, respectively. A total of 201 participants were recruited and examined for eligibility. Among them, 159 adults aged between 18 and 25 years were eligible in this study. No statistical difference was detected between the noise exposure and the low noise exposure groups using EHFA, DPOAE, and TEOAE (P > 0.05) except in the right ear at 4 kHz using TEOAE (abnormal rate 20.4% vs 5.2%, respectively; P = 0.05). CONCLUSION: These results showed TEOAE as the earliest indicator of minor pathology compared to DPOAE and EHFA. However, a multicenter controlled study or prospective study is essential to verify these results.

12.
Biol Chem ; 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35357096

RESUMO

Colorectal cancer (CRC) is a common cancer with poor prognosis. The research was designed to explore the role of PHF20L1 in angiogenesis and liver metastasis in CRC and discuss its molecular mechanism. Expression levels of PHF20L1, HIC1 and PAX2 in CRC tissues collected from CRC patients were detected using qRT-PCR, WB and immunohistochemical staining. CRC cells were transfected with PHF20L1, HIC1 and PAX2 overexpression or knockdown vectors and the proliferation, apoptosis, EMT and angiogenesis of the cells were determined. WB was utilized to assess protein levels of PHF20L1, HIC1, PAX2 and angiogenesis factor (ANGPT2, FGF1, PDGFA and VEGFA). The role of PHF20L1 regulating tumor formation and liver metastasis in vivo was detected as well. PHF20L1 was observed to express at a high level of CRC tissues. PHF20L1 promoted CRC cell growth, EMT and angiogenesis, and inhibited cell apoptosis. Knockdown of PHF20L1 had opposite effects on CRC cells. PHF20L1 negatively regulated HIC1 expression to promote PAX2 expression, thus promoting CRC cell progression. The in vivo results showed that PHF20L1 contributed to tumor formation and liver metastasis. PHF20L1 increases PAX2 expression to promote angiogenesis in CRC by inhibiting HIC1, therefore facilitating CRC cell EMT and liver metastasis. Our finding may provide a novel insight for CRC pathogenesis.

13.
Hepatology ; 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35243665

RESUMO

BACKGROUND AND AIMS: The loss of liver regenerative capacity is the most dramatic age-associated alteration. Because of an incomplete mechanistic understanding of the liver aging process, a successful therapeutic strategy to improve liver regeneration in the elderly has not been developed so far. Hepatocyte plasticity is a principal mechanism for producing new hepatocytes and cholangiocytes during regeneration. This study aims to promote the repopulation capacity of elderly hepatocytes by decoding the underlying mechanism about the regulation of aging on human hepatocyte plasticity. APPROACH AND RESULTS: To understand the age-related mechanisms, we established a hepatocyte aging model from human-induced pluripotent stem cells and developed a method for ex vivo characterization of hepatocyte plasticity. We found that hepatocyte plasticity was gradually diminished with aging, and the impaired plasticity was caused by age-induced histone hypoacetylation. Notably, selective inhibition of histone deacetylases could markedly restore aging-impaired plasticity. Based on these findings, we successfully improved the plasticity of elderly primary human hepatocytes that enhanced their repopulation capacity in the liver injury model. CONCLUSIONS: This study suggests that age-induced histone hypoacetylation impairs hepatocyte plasticity, and hepatocyte plasticity might be a therapeutic target for promoting the regenerative capacity of the elderly liver.

14.
Angew Chem Int Ed Engl ; : e202117703, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35233896

RESUMO

The construction of safe and environmentally-benign solid-state electrolytes (SSEs) with intrinsic hydroxide ion-conduction for flexible zinc-air batteries is highly desirable yet extremely challenging. Herein, hierarchically nanostructured CCNF-PDIL SSEs with reinforced concrete architecture are constructed by nanoconfined polymerization of dual-cation ionic liquid (PDIL, concrete) within a robust three-dimensional porous cationic cellulose nanofiber matrix (CCNF, reinforcing steel), where plenty of penetrating ion-conductive channels are formed and undergo dynamic self-rearrangement under different hydrated levels. The CCNF-PDIL SSEs synchronously exhibit good flexibility, mechanical robustness, superhigh ion conductivity of 286.5 mS cm-1 , and decent water uptake. The resultant flexible solid-state zinc-air batteries deliver a high-power density of 135 mW cm-2 , a specific capacity of 775 mAh g-1 and an ultralong cycling stability with continuous operation of 240 hours for 720 cycles, far outperforming those of the state-of-the-art solid-state batteries. The marriage of biomaterials with the diversity of ionic liquids creates enormous opportunities to construct advanced SSEs for solid-state batteries.

15.
Cancer Control ; 29: 10732748221076820, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35271403

RESUMO

BACKGROUND: Our purpose is to develop a model combining radiomic features of radiotherapy localisation computed tomography and clinical characteristics that can be used to estimate overall survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy following induction chemotherapy. METHODS: We recruited 145 patients with pathologically confirmed nasopharyngeal carcinoma between February 2012 and April 2015. In total, 851 radiomic features were extracted from radiotherapy localisation computed tomography images for the gross tumour volume of the nasopharynx and the gross tumour volume of neck metastatic lymph nodes. The least absolute shrinkage and selection operator algorithm was applied to select radiomics features, build the model and calculate the Rad-score. The patients were divided into high- and low-risk groups based on their Rad-scores. A nomogram for estimating overall survival based on both radiomic and clinical features was generated using multivariate Cox regression hazard models. Prediction reliability was evaluated using Harrell's concordance index. RESULTS: In total, seven radiomic features and one clinical characteristic were extracted for survival analysis, and the combination of radiomic and clinical features was a better predictor of overall survival (concordance index = .849 [confidence interval: .782-.916]) than radiomic features (concordance index = .793 [confidence interval: .697-.890]) or clinical characteristics (concordance index = .661 [confidence interval: .673-.849]) alone. CONCLUSION: Our results show that a nomogram combining radiomic features of radiotherapy localisation computed tomography and clinical characteristics can predict overall survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy following induction chemotherapy more effectively than radiomic features or clinical characteristics alone.


Assuntos
Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Quimioterapia de Indução , Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Prognóstico , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X/métodos
16.
Adv Mater ; 34(19): e2110518, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35257424

RESUMO

Two decades after the rapid expansion of photovoltaics, the number of solar panels reaching end-of-life is increasing. While precious metals such as silver and copper are usually recycled, silicon, which makes up the bulk of a solar cells, goes to landfills. This is due to the defect- and impurity-sensitive nature in most silicon-based technologies, rendering it uneconomical to purify waste silicon. Thermoelectrics represents a rare class of material in which defects and impurities can be engineered to enhance the performance. This is because of the majority-carrier nature, making it defect- and impurity-tolerant. Here, the upcycling of silicon from photovoltaic (PV) waste into thermoelectrics is enabled. This is done by doping 1% Ge and 4% P, which results in a figure of merit (zT) of 0.45 at 873 K, the highest among silicon-based thermoelectrics. The work represents an important piece of the puzzle in realizing a circular economy for photovoltaics and electronic waste.

17.
Adv Mater ; : e2201547, 2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35307897

RESUMO

With the rising level of atmospheric CO2 worsening climate change, a promising global movement toward carbon neutrality is forming. Sustainable CO2 management based on carbon capture and utilization (CCU) has garnered considerable interest due to its critical role in resolving emission-control and energy-supply challenges. Here, a comprehensive review is presented that summarizes the state-of-the-art progress in developing promising materials for sustainable CO2 management in terms of not only capture, catalytic conversion (thermochemistry, electrochemistry, photochemistry, and possible combinations), and direct utilization, but also emerging integrated capture and in situ conversion as well as artificial-intelligence-driven smart material study. In particular, insights that span multiple scopes of material research are offered, ranging from mechanistic comprehension of reactions, rational design and precise manipulation of key materials (e.g., carbon nanomaterials, metal-organic frameworks, covalent organic frameworks, zeolites, ionic liquids), to industrial implementation. This review concludes with a summary and new perspectives, especially from multiple aspects of society, which summarizes major difficulties and future potential for implementing advanced materials and technologies in sustainable CO2 management. This work may serve as a guideline and road map for developing CCU material systems, benefiting both scientists and engineers working in this growing and potentially game-changing area.

19.
Materials (Basel) ; 15(5)2022 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-35268993

RESUMO

In this paper, the mechanical properties of coral concrete with different strength and different polyvinyl alcohol (PVA) fiber content under compression were experimentally investigated. The results show that adding an appropriate amount of PVA fiber could obtain satisfactory mechanical properties of coral concrete. The stress-strain constitutive relationship of plain and PVA fiber-reinforced coral concrete was investigated by prism uniaxial compression test. The results shown that the incorporation of PVA fiber had a significant effect on limiting the development of concrete internal cracks, and effectively improved the mechanical properties of coral concrete after cracking, especially the toughness. Different constitutive models from previous research were used to describe the axial compressive stress-strain relationship of plain and PVA fiber-reinforced coral concrete, and a piecewise function model was finally selected which is most consistent with the experimental curve and its characteristic points. In addition, determination of critical parameters for the selected constitutive model was proposed, and experimental validations confirmed its accuracy.

20.
Antioxidants (Basel) ; 11(3)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35326123

RESUMO

Mitochondria are important organelles that act as a primary site to produce reactive oxygen species (ROS). Additionally, mitochondria play a pivotal role in the regulation of Ca2+ signaling, fatty acid oxidation, and ketone synthesis. Dysfunction of these signaling molecules leads to the development of pulmonary hypertension (PH), atherosclerosis, and other vascular diseases. Features of PH include vasoconstriction and pulmonary artery (PA) remodeling, which can result from abnormal proliferation, apoptosis, and migration of PA smooth muscle cells (PASMCs). These responses are mediated by increased Rieske iron-sulfur protein (RISP)-dependent mitochondrial ROS production and increased mitochondrial Ca2+ levels. Mitochondrial ROS and Ca2+ can both synergistically activate nuclear factor κB (NF-κB) to trigger inflammatory responses leading to PH, right ventricular failure, and death. Evidence suggests that increased mitochondrial ROS and Ca2+ signaling leads to abnormal synthesis of ketones, which play a critical role in the development of PH. In this review, we discuss some of the recent findings on the important interactive role and molecular mechanisms of mitochondrial ROS and Ca2+ in the development and progression of PH. We also address the contributions of NF-κB-dependent inflammatory responses and ketone-mediated oxidative stress due to abnormal regulation of mitochondrial ROS and Ca2+ signaling in PH.

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