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1.
Nat Commun ; 15(1): 8628, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39366998

RESUMO

The IL-23-Th17 axis is responsible for neutrophilic inflammation in various inflammatory diseases. Here, we discover a potential pathway to inhibit neutrophilic asthma. In our neutrophil-dominant asthma (NDA) model, single-cell RNA-seq analysis identifies a subpopulation of CD39+CD9+ interstitial macrophages (IMs) suppressed by IL-23 in NDA conditions but increased by an IL-23 inhibitor αIL-23p19. Adoptively transferred CD39+CD9+ IMs suppress neutrophil extracellular trap formation (NETosis), a representative phenotype of NDA, and also Th17 cell activation and neutrophilic inflammation. CD39+CD9+ IMs first attach to neutrophils in a CD9-dependent manner, and then remove ATP near neutrophils that contribute to NETosis in a CD39-dependent manner. Transcriptomic data from asthmatic patients finally show decreased CD39+CD9+ IMs in severe asthma than mild/moderate asthma. Our results suggest that CD39+CD9+ IMs function as a potent negative regulator of neutrophilic inflammation by suppressing NETosis in the IL-23-Th17 axis and can thus serve as a potential therapeutic target for IL-23-Th17-mediated neutrophilic asthma.


Assuntos
Apirase , Asma , Armadilhas Extracelulares , Interleucina-23 , Neutrófilos , Tetraspanina 29 , Células Th17 , Asma/imunologia , Asma/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Interleucina-23/metabolismo , Interleucina-23/imunologia , Humanos , Animais , Apirase/metabolismo , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/imunologia , Tetraspanina 29/metabolismo , Tetraspanina 29/genética , Camundongos , Feminino , Masculino , Pulmão/imunologia , Pulmão/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Antígenos CD
2.
Nutrients ; 16(19)2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39408352

RESUMO

BACKGROUND: Recent studies suggest a critical role for vitamin D in respiratory diseases, including asthma and allergic rhinitis. However, the relationship between vitamin D deficiency and chronic rhinitis, particularly in middle- and older-aged populations, remains underexplored. This study aimed to investigate the association between vitamin D deficiency and chronic rhinitis in middle- and older-aged adults while controlling for lifestyle and physical status factors. METHODS: Data from 12,654 participants aged 40 years and older were analyzed from the fifth Korean National Health and Nutrition Examination Survey (2010-2012). The prevalence of chronic rhinitis and its association with serum vitamin D levels were assessed using multiple logistic regression models, adjusting for demographic, lifestyle, and physical characteristics. RESULTS: The prevalence of chronic rhinitis was 21.1%. Participants with chronic rhinitis had a higher prevalence of vitamin D deficiency (69.9% vs. 65.2%) and lower mean vitamin D levels (17.73 ng/mL vs. 18.19 ng/mL) compared to those without chronic rhinitis. After adjusting for confounding factors, vitamin D deficiency remained significantly associated with an increased likelihood of chronic rhinitis (OR = 1.21, 95% CI, 1.082-1.348, p = 0.001). CONCLUSIONS: This study identifies a significant association between vitamin D deficiency and chronic rhinitis in middle- and older-aged adults, suggesting that maintaining adequate vitamin D levels may be important in managing chronic rhinitis.


Assuntos
Inquéritos Nutricionais , Rinite , Deficiência de Vitamina D , Vitamina D , Humanos , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Rinite/epidemiologia , Rinite/sangue , Idoso , Doença Crônica/epidemiologia , Vitamina D/sangue , Vitamina D/análogos & derivados , Prevalência , República da Coreia/epidemiologia , Adulto , Fatores de Risco , Estudos Transversais , Modelos Logísticos
3.
Cureus ; 16(8): e68165, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39347269

RESUMO

BACKGROUND: Walking is widely recognized as a prevalent form of daily exercise worldwide. However, fewer studies have explored the health outcomes of different intensities of walking exercise for older adults. Thus, the study aimed to investigate the effects of walking at different exercise intensities on body composition, emotions, cognition, and physical function among older adults. PURPOSE: This study aimed to investigate the effects of walking at different exercise intensities on body composition, emotions, cognition, and physical function after eight weeks of group walking. Specifically, the study focused on the potential benefits of high-intensity interval walking (HIIW), exploring whether HIIW could have a more positive impact on the physical function and overall health of older adults compared to moderate-intensity continuous walking (MICW). METHODS: Participants aged 65 years or older were randomly assigned to either HIIW (n=13, 85% HRmax and 55% HRmax, alternating every three minutes) or MICW (n=13, 70% HRmax), engaging in group walking exercises for 30 minutes three times a week. The pre-test and post-test evaluations included body composition, cognition, emotions, and physical function. RESULTS: The two-minute step test showed significant improvements over time (p<0.0001) and time-group interaction (p=0.004), and sit and reach showed significant changes over time (p<0.0001). The independent T-test showed significant differences between the HIIW and MICW groups (two-minute step test: t (24)=1.80, p=0.04; sit and reach test: t (19)=3.65, p<0.001) at post-measurement. Additionally, no significant differences were found in body composition (weight, p=0.74; body mass index (BMI), p=0.35; body fat mass, p=0.45; skeletal muscle mass (SMM), p=0.77), emotions (geriatric depression scale (GDS), p=0.79; quality of life (QOL), p=0.54; Pittsburgh Sleep Quality Index, p=0.24), and cognitive function (CoSAS total score, p=0.25) between the HIIW and MICW groups after exercise. Grip strength, balance, 30-second chair stand, back scratch, and eight-foot up and go tests showed no significant effects in the time-group interaction. CONCLUSION: Regular HIIW exercise has positive effects on physical functions such as cardiorespiratory endurance and flexibility in older adults, indicating the potential for establishing a foundation for developing customized exercise programs in the future.

4.
J Ginseng Res ; 48(4): 354-365, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39036733

RESUMO

Panax species include Panax ginseng Meyer, Panax quinquefolium L., Panax notoginseng, Panax japonicum, Panax trifolium, and Panax pseudoginseng, which contain bioactive components (BCs) such as ginsenosides and polysaccharides. Recently, growing evidence has revealed the pharmacological effects of Panax species and their BCs on allergic airway diseases (AADs), including allergic asthma (AA) and allergic rhinitis (AR). AADs are characterized by damaged epithelium, sustained acquired immune responses with enforced Th2 responses, allergen-specific IgE production, and enhanced production of histamine and leukotrienes by activated mast cells and basophils. In this review, we summarize how Panax species and their BCs modulate acquired immune responses involving interactions between dendritic cells and T cells, reduce the pro-inflammatory responses of epithelial cells, and reduce allergenic responses from basophils and mast cells in vitro. In addition, we highlight the current understanding of the alleviative effects of Panax species and their BCs against AA and AR in vivo. Moreover, we discuss the unmet needs of research and considerations for the treatment of patients to provide basic scientific knowledge for the treatment of AADs using Panax species and their BCs.

5.
Antioxidants (Basel) ; 13(4)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38671920

RESUMO

Phosphatase and tensin homolog (PTEN) is a negative regulator of the phosphoinositide 3-kinases/protein kinase B (PI3K/AKT) signaling pathway. Notably, its active site contains a cysteine residue that is susceptible to oxidation by hydrogen peroxide (H2O2). This oxidation inhibits the phosphatase function of PTEN, critically contributing to the activation of the PI3K/AKT pathway. Upon the stimulation of cell surface receptors, the activity of NADPH oxidase (NOX) generates a transient amount of H2O2, serving as a mediator in this pathway by oxidizing PTEN. The mechanism underlying this oxidation, occurring despite the presence of highly efficient and abundant cellular oxidant-protecting and reducing systems, continues to pose a perplexing conundrum. Here, we demonstrate that the presence of bicarbonate (HCO3-) promoted the rate of H2O2-mediated PTEN oxidation, probably through the formation of peroxymonocarbonate (HCO4-), and consequently potentiated the phosphorylation of AKT. Acetazolamide (ATZ), a carbonic anhydrase (CA) inhibitor, was shown to diminish the oxidation of PTEN. Thus, CA can also be considered as a modulator in this context. In essence, our findings consolidate the crucial role of HCO3- in the redox regulation of PTEN by H2O2, leading to the presumption that HCO4- is a signaling molecule during cellular physiological processes.

6.
Antioxidants (Basel) ; 13(2)2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38397797

RESUMO

Phosphatase and tensin homolog (PTEN) is a tumor suppressor due to its ability to regulate cell survival, growth, and proliferation by downregulating the PI3K/AKT signaling pathway. In addition, PTEN plays an essential role in other physiological events associated with cell growth demands, such as ischemia-reperfusion, nerve injury, and immune responsiveness. Therefore, recently, PTEN inhibition has emerged as a potential therapeutic intervention in these situations. Increasing evidence demonstrates that reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), are produced and required for the signaling in many important cellular processes under such physiological conditions. ROS have been shown to oxidize PTEN at the cysteine residue of its active site, consequently inhibiting its function. Herein, we provide an overview of studies that highlight the role of the oxidative inhibition of PTEN in physiological processes.

7.
Antioxidants (Basel) ; 13(1)2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38247533

RESUMO

The process of cellular senescence, which is characterized by stable cell cycle arrest, is strongly associated with dysfunctional cellular metabolism and circadian rhythmicity, both of which are reported to result from and also be causal to cellular senescence. As a result, modifying any of them-senescence, metabolism, or the circadian clock-may affect all three simultaneously. Obesity accelerates aging by disrupting the homeostasis of reactive oxygen species (ROS) via an increased mitochondrial burden of fatty acid oxidation. As a result, if senescence, metabolism, and circadian rhythm are all linked, anti-obesity treatments may improve metabolic regulation while also alleviating senescence and circadian rhythm. Vutiglabridin is a small molecule in clinical trials that improves obesity by enhancing mitochondrial function. We found that chronic treatment of senescent primary human dermal fibroblasts (HDFs) with vutiglabridin alleviates all investigated markers of cellular senescence (SA-ß-gal, CDKN1A, CDKN2A) and dysfunctional cellular circadian rhythm (BMAL1) while remarkably preventing the alterations of mitochondrial function and structure that occur during the process of cellular senescence. Our results demonstrate the significant senescence-alleviating effects of vutiglabridin, specifically with the restoration of cellular circadian rhythmicity and metabolic regulation. These data support the potential development of vutiglabridin against aging-associated diseases and corroborate the intricate link between cellular senescence, metabolism, and the circadian clock.

8.
Nat Commun ; 15(1): 46, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167804

RESUMO

Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.


Assuntos
Longevidade , Receptor 5 Toll-Like , Animais , Camundongos , Flagelina/metabolismo , Mucosa Intestinal/metabolismo , Longevidade/genética , Pulmão/metabolismo
9.
Pharmacol Ther ; 252: 108560, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37952903

RESUMO

Biological responsiveness refers to the capacity of living organisms to adapt to changes in both their internal and external environments through physiological and behavioral mechanisms. One of the prominent aspects of aging is the decline in this responsiveness, which can lead to a deterioration in the processes required for maintenance, survival, and growth. The vital link between physiological responsiveness and the essential life processes lies within the signaling systems. To devise effective strategies for controlling the aging process, a comprehensive reevaluation of this connecting loop is imperative. This review aims to explore the impact of aging on signaling systems responsible for responsiveness and introduce a novel perspective on intervening in the aging process by restoring the compromised responsiveness. These innovative mechanistic approaches for modulating altered responsiveness hold the potential to illuminate the development of action plans aimed at controlling the aging process and treating age-related disorders.


Assuntos
Envelhecimento , Transdução de Sinais , Humanos , Envelhecimento/fisiologia
10.
Aging Male ; 26(1): 2257302, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37812685

RESUMO

BACKGROUND: With the rapid increase in population longevity, more clinical attention is being paid to the overall health of long-lived people, especially centenarians. Subjective health, which is the perception of one's health status, predicts both mortality and declining physical function in older adults. The purpose of this study was to investigate the factors related to subjective health among centenarians and near-centenarians (ages ≥95) living in a rural area of South Korea. METHODS: A total of 101 participants were enrolled from four different regions (Gurye, Gokseong, Sunchang, and Damyang), known as the Longevity Belt in Korea. Variables assessing physical and mental health, including the results of blood tests, were examined. Factors associated with good subjective health were identified with logistic regression analysis. RESULTS: Fifty-six participants (59.6%) were subjectively healthy among the centenarians and near-centenarians. Logistic regression analysis revealed that depressive mood was the only factor associated with subjective health and was negatively correlated. The regression model explained 39% of the variance in subjective health. CONCLUSIONS: These findings emphasize the importance of mental health at very advanced ages. Because depressive mood negatively correlates with subjective health, more attention is needed to prevent and manage mood symptoms of people of advanced ages, including centenarians.


Assuntos
Centenários , Depressão , Idoso de 80 Anos ou mais , Humanos , Idoso , Depressão/epidemiologia , Estudos Transversais , Autoavaliação Diagnóstica , Longevidade
11.
Proc Natl Acad Sci U S A ; 120(33): e2300036120, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37549292

RESUMO

While the world is rapidly transforming into a superaging society, pharmaceutical approaches to treat sarcopenia have hitherto not been successful due to their insufficient efficacy and failure to specifically target skeletal muscle cells (skMCs). Although electrical stimulation (ES) is emerging as an alternative intervention, its efficacy toward treating sarcopenia remains unexplored. In this study, we demonstrate a silver electroceutical technology with the potential to treat sarcopenia. First, we developed a high-throughput ES screening platform that can simultaneously stimulate 15 independent conditions, while utilizing only a small number of human-derived primary aged/young skMCs (hAskMC/hYskMC). The in vitro screening showed that specific ES conditions induced hypertrophy and rejuvenation in hAskMCs, and the optimal ES frequency in hAskMCs was different from that in hYskMCs. When applied to aged mice in vivo, specific ES conditions improved the prevalence and thickness of Type IIA fibers, along with biomechanical attributes, toward a younger skMC phenotype. This study is expected to pave the way toward an electroceutical treatment for sarcopenia with minimal side effects and help realize personalized bioelectronic medicine.


Assuntos
Sarcopenia , Animais , Humanos , Camundongos , Fibras Musculares Esqueléticas , Músculo Esquelético/fisiologia , Fenótipo , Sarcopenia/terapia , Prata
12.
Sci Transl Med ; 15(711): eabh3489, 2023 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-37647389

RESUMO

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis. Reduced PGC-1α abundance is linked to skeletal muscle weakness in aging or pathological conditions, such as neurodegenerative diseases and diabetes; thus, elevating PGC-1α abundance might be a promising strategy to treat muscle aging. Here, we performed high-throughput screening and identified a natural compound, farnesol, as a potent inducer of PGC-1α. Farnesol administration enhanced oxidative muscle capacity and muscle strength, leading to metabolic rejuvenation in aged mice. Moreover, farnesol treatment accelerated the recovery of muscle injury associated with enhanced muscle stem cell function. The protein expression of Parkin-interacting substrate (PARIS/Zfp746), a transcriptional repressor of PGC-1α, was elevated in aged muscles, likely contributing to PGC-1α reduction. The beneficial effect of farnesol on aged muscle was mediated through enhanced PARIS farnesylation, thereby relieving PARIS-mediated PGC-1α suppression. Furthermore, short-term exercise increased PARIS farnesylation in the muscles of young and aged mice, whereas long-term exercise decreased PARIS expression in the muscles of aged mice, leading to the elevation of PGC-1α. Collectively, the current study demonstrated that the PARIS-PGC-1α pathway is linked to muscle aging and that farnesol treatment can restore muscle functionality in aged mice through increased farnesylation of PARIS.


Assuntos
Farneseno Álcool , Debilidade Muscular , Animais , Camundongos , Farneseno Álcool/farmacologia , Envelhecimento , Prenilação , Ubiquitina-Proteína Ligases
13.
J Invest Dermatol ; 143(11): 2295-2310.e17, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37211200

RESUMO

An effective healing response is critical to healthy aging. In particular, energy homeostasis has become increasingly recognized as a factor in effective skin regeneration. ANT2 is a mediator of adenosine triphosphate import into mitochondria for energy homeostasis. Although energy homeostasis and mitochondrial integrity are critical for wound healing, the role played by ANT2 in the repair process had not been elucidated to date. In our study, we found that ANT2 expression decreased in aged skin and cellular senescence. Interestingly, overexpression of ANT2 in aged mouse skin accelerated the healing of full-thickness cutaneous wounds. In addition, upregulation of ANT2 in replicative senescent human diploid dermal fibroblasts induced their proliferation and migration, which are critical processes in wound healing. Regarding energy homeostasis, ANT2 overexpression increased the adenosine triphosphate production rate by activating glycolysis and induced mitophagy. Notably, ANT2-mediated upregulation of HSPA6 in aged human diploid dermal fibroblasts downregulated proinflammatory genes that mediate cellular senescence and mitochondrial damage. This study shows a previously uncharacterized physiological role of ANT2 in skin wound healing by regulating cell proliferation, energy homeostasis, and inflammation. Thus, our study links energy metabolism to skin homeostasis and reports, to the best of our knowledge, a previously unreported genetic factor that enhances wound healing in an aging model.

14.
Allergy Asthma Immunol Res ; 15(2): 145-159, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37021502

RESUMO

Allergic rhinitis is the most common chronic disease worldwide. Various upper airway symptoms lower quality of life, and due to the recurrent symptoms, multiple treatments are usually attempted rather than one definitive treatment. There are alternatives to medical (medication-based) and non-medical treatments. A guideline is needed to understand allergic rhinitis and develop an appropriate treatment plan. We have developed guidelines for medical treatment based on previous reports. The current guidelines herein are associated with the "KAAACI Evidence-Based Guidelines for Allergic Rhinitis in Korea, Part 1: Update in pharmacotherapy" in which we aimed to provide evidence-based recommendations for the medical treatment of allergic rhinitis. Part 2 focuses on non-pharmacological management, including allergen-specific immunotherapy, subcutaneous or sublingual immunotherapy, nasal saline irrigation, environmental management strategies, companion animal management, and nasal turbinate surgery. The evidence to support the treatment efficacy, safety, and selection has been systematically reviewed. However, larger controlled studies are needed to elevate the level of evidence to select rational non-medical therapeutic options for patients with allergic rhinitis.

15.
Antioxidants (Basel) ; 12(4)2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37107309

RESUMO

Mitochondria are one of the organelles undergoing rapid alteration during the senescence process. Senescent cells show an increase in mitochondrial size, which is attributed to the accumulation of defective mitochondria, which causes mitochondrial oxidative stress. Defective mitochondria are also targets of mitochondrial oxidative stress, and the vicious cycle between defective mitochondria and mitochondrial oxidative stress contributes to the onset and development of aging and age-related diseases. Based on the findings, strategies to reduce mitochondrial oxidative stress have been suggested for the effective treatment of aging and age-related diseases. In this article, we discuss mitochondrial alterations and the consequent increase in mitochondrial oxidative stress. Then, the causal role of mitochondrial oxidative stress on aging is investigated by examining how aging and age-related diseases are exacerbated by induced stress. Furthermore, we assess the importance of targeting mitochondrial oxidative stress for the regulation of aging and suggest different therapeutic strategies to reduce mitochondrial oxidative stress. Therefore, this review will not only shed light on a new perspective on the role of mitochondrial oxidative stress in aging but also provide effective therapeutic strategies for the treatment of aging and age-related diseases through the regulation of mitochondrial oxidative stress.

16.
Int Forum Allergy Rhinol ; 13(10): 1926-1936, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36932634

RESUMO

BACKGROUND: Calprotectin is an antimicrobial peptide primarily secreted by neutrophils. Furthermore, calprotectin secretion increases in patients with chronic rhinosinusitis (CRS) with polyps (CRSwNP) and positively correlates with neutrophil markers. However, CRSwNP is known to be associated with type 2 inflammation related to tissue eosinophilia. Therefore, the authors investigated calprotectin expression in eosinophils and eosinophil extracellular traps (EETs) and explored the associations between tissue calprotectin and the clinical findings of patients with CRS. METHODS: A total of 63 patients participated, and patients diagnosed with CRS were classified based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score. The authors performed hematoxylin and eosin staining, immunohistochemistry, immunofluorescence with calprotectin, myeloperoxidase (MPO), major basic protein (MBP), and citrullinated histone H3 with the participant's tissues. Finally, correlations between calprotectin and the clinical data were examined. RESULTS: Calprotectin-positive cells are co-localized not only in MPO-positive cells but also in MBP-positive cells in human tissues. Calprotectin was also involved in EETs and neutrophil extracellular traps. The number of calprotectin-positive cells in the tissue was positively correlated with the number of tissue and blood eosinophils. In addition, calprotectin in the tissue is associated with the olfactory function, Lund-Mackay computed tomography score, and JESREC score. CONCLUSIONS: Calprotectin, known to be secreted by neutrophils, in CRS was also expressed in eosinophils. In addition, calprotectin, which functions as an antimicrobial peptide, may play an important role in the innate immune response based on its EET involvement. Therefore, calprotectin expression could reflect as a disease severity biomarker for CRS.


Assuntos
Armadilhas Extracelulares , Pólipos Nasais , Rinite , Sinusite , Humanos , Armadilhas Extracelulares/metabolismo , Complexo Antígeno L1 Leucocitário , Rinite/diagnóstico , Sinusite/diagnóstico , Eosinófilos , Doença Crônica , Pólipos Nasais/metabolismo
17.
Antioxidants (Basel) ; 12(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36670982

RESUMO

Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are becoming increasingly prevalent worldwide. Despite the different etiologies, their spectra and histological feature are similar, from simple steatosis to more advanced stages such as steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Studies including peroxiredoxin knockout models revealed that oxidative stress is crucial in these diseases, which present as consequences of redox imbalance. Protein tyrosine phosphatases (PTPs) are a superfamily of enzymes that are major targets of reactive oxygen species (ROS) because of an oxidation-susceptible nucleophilic cysteine in their active site. Herein, we review the oxidative inactivation of two tumor suppressor PTPs, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and T-cell protein tyrosine phosphatase (TCPTP), and their contribution to the pathogenicity of ALD and NAFLD, respectively. This review might provide a better understanding of the pathogenic mechanisms of these diseases and help develop new therapeutic strategies to treat fatty liver disease.

18.
Allergy Asthma Immunol Res ; 15(1): 19-31, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36693355

RESUMO

The prevalence of allergic rhinitis (AR) and the socioeconomic burden associated with the medical cost and quality of life (QOL) of AR have progressively increased. Therefore, practical guidelines for the appropriate management of AR need to be developed based on scientific evidence while considering the real-world environment, values, and preferences of patients and physicians. The Korean Academy of Asthma, Allergy and Clinical Immunology revised clinical guidelines of AR to address key clinical questions of the management of AR. Part 1 of the revised guideline covers the pharmacological management of patients with AR in Korea. Through a meta-analysis and systematic review, we made 4 recommendations for AR pharmacotherapy, including intranasal corticosteroid (INCS)/intranasal antihistamine (INAH) combination therapy, oral antihistamine/INCS combination therapy, leukotriene receptor antagonist treatment in AR patients with asthma, and prophylactic treatment for patients with pollen-induced AR. However, all recommendations are conditional because of the low or very low evidence of certainty. Well-designed and strictly executed randomized controlled trials are needed to measure and report appropriate outcomes.

19.
Exp Gerontol ; 173: 112091, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36657533

RESUMO

Senescence is a phenomenon defined by alterations in cellular organelles and is the primary cause of aging and aging-related diseases. Recent studies have shown that oncogene-induced senescence is driven by activation of serine/threonine protein kinases (AKT1, AKT2 and AKT3). In this study, we evaluated twelve AKT inhibitors and revealed GDC0068 as a potential agent to ameliorate senescence. Senescence-ameliorating effect was evident from the finding that GDC0068 yielded lysosomal functional recovery as observed by reduction in lysosomal mass and induction in autophagic flux. Furthermore, GDC0068-mediated restoration of lysosomal function activated the removal of dysfunctional mitochondria, resulting in restoration of mitochondrial function. Together, our findings revealed a unique mechanism by which senescence is recovered by functional restoration of lysosomes and mitochondria through modulation of AKT activity.


Assuntos
Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Autofagia , Lisossomos/metabolismo , Mitocôndrias/metabolismo , Senescência Celular
20.
JAMA Otolaryngol Head Neck Surg ; 149(1): 15-23, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36394879

RESUMO

Importance: Turbinate surgery is an effective treatment for allergic rhinitis (AR) refractory to medical treatment. However, the long-term outcomes of turbinate surgery are still unclear and have not yet been confirmed by a meta-analysis and systematic review of the literature. Objective: To investigate the long-term outcomes and safety of turbinate surgery in AR by performing a meta-analysis. Data Sources: MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov were searched through April 2021. Study Selection: Studies that analyzed turbinate surgery alone, had a follow-up period of more than 1 year, examined long-term efficacy of turbinate surgery, used current turbinate surgery methods, and were published in a peer-reviewed journal were included. Full-text reviews were performed by 2 independent reviewers. Conflicts were resolved by a third reviewer. Data Extraction and Synthesis: Descriptive and quantitative data were extracted; weighted mean difference (WMD) was synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic and the I2 metric. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Main Outcomes and Measures: The long-term outcomes of turbinate surgery on subjective nasal symptoms and objective parameters. Results: Of the 3962 citations retrieved, 18 studies comprising 1411 patients were included. Findings showed significantly decreased symptom scores in nasal obstruction (WMD, 4.60, 95% CI, 3.43-5.76), rhinorrhea (WMD, 3.12; 95% CI, 1.97-4.28), sneezing (WMD, 2.64; 95% CI, 1.74-3.54), itching (WMD, 1.75; 95% CI, 1.20-2.30), and nasal resistance (WMD, 0.16; 95% CI, 0.08-0.24) and a significant increased total nasal volume (WMD, 0.96; 95% CI, 0.73-1.19). There was no significant difference in the occurrence of any complication. More than 1 year after surgery, the improvements in nasal obstruction (WMD, 5.18; 95% CI, 3.00-7.37), rhinorrhea (WMD, 3.57; 95% CI, 1.78-5.37), and sneezing (WMD, 2.95; 95% CI, 1.58-4.32) were maintained. Conclusions and Relevance: In this systematic review and meta-analysis, turbinate surgery was associated with positive outcomes in AR and maintained the association during long-term follow-up. The rate of complications is also low. These findings can guide the preoperative counseling of patients with AR being considered for turbinate surgery.


Assuntos
Obstrução Nasal , Rinite Alérgica , Humanos , Conchas Nasais/cirurgia , Obstrução Nasal/cirurgia , Obstrução Nasal/etiologia , Espirro , Rinite Alérgica/cirurgia , Rinite Alérgica/complicações , Rinorreia
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