Present Review Research Articles

Using heart rate variability to predict neurological outcomes in preterm infants: a scoping review.

Infants born preterm are at higher risk of neurological complications, including intraventricular haemorrhage and white matter injury. After discharge, these infants may experience adverse neurodevelopmental outcomes and exhibit lower educational attainment. Early detection of brain injury and accurate prediction of neurodevelopmental impairment would allow early intervention and support. Heart rate variability (HRV) describes the variation of time intervals between each subsequent heartbeat. HRV is controlled by the autonomic nervous system, which may be affected by hypoxia and compromised blood flow. While HRV has primarily been investigated in neonatal sepsis, the association between HRV, brain injury and neurodevelopmental outcomes in preterm infants is less established. The present scoping review examines the utility of HRV monitoring for predicting short-term and long-term neurological outcomes in preterm infants. Following systematic search of Medline, Embase, Web of Science and the Cochrane Library, 15 studies were included. Nine studies examined the relationship between HRV and brain injury, with all but two showed an association. Eight studies examined the relationship between HRV and long-term outcomes and all eight found an association. This scoping review suggests that decreased HRV in the neonatal period is associated with short- and long-term neurodevelopmental outcomes in preterm infants. IMPACT: Changes in heart rate variability correlate with the occurrence of intraventricular haemorrhage in preterm infants. A decrease in heart rate variability may precede the development of intraventricular haemorrhage. Alterations in heart rate variability correlate with long-term neurodevelopmental outcomes. Significant variability exists in metrics used in assessing heart rate variability.

Lichen striatus: a review.

Lichen striatus (LS) is an acquired blaschkitis, with typical linear and unilateral distribution. It occurs mainly in children and is self-resolving, yet its etiopathogenesis remains widely unknown. A review of the literature on LS cases was performed using the keyword "lichen striatus" to retrieve all relevant articles through PubMed and Google Scholar. A total of 27 articles describing 440 LS patients were included in the present review. Mean age of patients was 3.8 years; male: female: ratio was 1:1.9. The present review confirms LS as a primarily pediatric condition, mainly affecting females. Dysregulation of the immune system might be involved in its pathogenesis, with cytotoxic T-cells attacking mosaic keratinocytes after loss of immune tolerance. The review confirms LS is mainly diagnosed clinically (80%) based on its clinical characteristics: erythematous (70%) or hypopigmented (24%) papules, distributed along the lines of Blashko. The benignity of this clinical entity is suggested by the rather short duration of disease (9.5 months on average) and by the uncommonness of therapy, adopted in only 20% of cases, and when needed, administered topically. This review examines the complexities of LS but acknowledges limitations in data sources and calls for further research.

Surgical decisions on implant-related parameters can enhance knowledge transfer for glenoid bone grafting in primary reverse shoulder arthroplasty: a scoping review of heterogeneity sources.

The purpose of the present scoping review is to identify sources of heterogeneity in reporting domains that have the potential to improve surgical decision-making in reverse shoulder arthroplasty associated with glenoid bone grafting. A scoping review was conducted according to the JBI and PRISMA ScR guidelines. Articles covering glenoid bone grafting at the time of reverse shoulder replacement, published between 2012 and 2022 in MEDLINE, Scopus, Epistemonikos, Web of Science, and Cochrane Database of Systematic Reviews, were searched. Reporting of core outcome measures, as well as prosthesis-related variables, rehabilitation protocols, radiographic evaluation methods, and bone graft incorporation assessments, were collected. For the final analysis, a total of 14 articles were considered. There were 649 operated shoulders with a mean patient age of 72 years, ranging from 48 to 85 years. Analysis of preoperative ranges of motion and patient-reported outcome measures revealed increased heterogeneity in patient selection between studies. Reporting of implant-related parameters was the most inconsistent. Rehabilitation protocols were scarcely reported. Assessment of graft incorporation and radiographic evaluation of choice revealed that there is no consistent method or measurement and the clinical relevance of radiolucent lines at the graft-glenoid bone interface is unclear. Addressing implant-related reporting gaps has the highest potential to improve surgical decision-making and provide orthopedic surgeons with a more comprehensive understanding of published results on glenoid bone grafting at the time of primary reverse shoulder arthroplasty.

Recent opportunities and application of gellan gum based drug delivery system for intranasal route.

In the recent years, in-situ hydrogel based on gellan gum has been investigated for delivery of various drug molecules particularly to treat neurological disorders via intranasal route. The major objective of the present manuscript is to review the recent research studies exploring gellan gum as ionic triggered in-situ gel for intranasal administration to enhance absorption of drugs and to increase their therapeutic efficacy. This review include literature from 1982 to 2023 and were collected from various scientific electronic databases like Scopus, PubMed and Google Scholar to review source, chemistry, ionotropic gelation mechanism, and recent research studies for gellan gum based in-situ hydrogel for intransasl administration.Keywords such as gellan gum, in-situ hydrogel, intranasal administration and brain targeting were used to search literature. The present review included the research studies which explored gellan gum based in-situ gel for intranasal drug delivery. The findings have shown enhanced biavailability of various drugs upon intranasal administration using gellan-gum based in-situ hydrogel.Moreover, the review indicated that intranasal administration of in-situ hydrogel facilitate to overcome blood brain barrier effectively. Hence, significantly higher drug concentration was found to be achieved in brain tissues upon intranasal administration than that of other routes like oral and intravenous. The present work conducted a comprehensive review for gellan gum based in-situ hydrogel particularly for intransal administration to overcome BBB. The study concluded that gellan gum based in-situ hydrogel could be potential promising delivery system for intranasal administration to improve bioavailability and efficacy of drugs specifically to treat neurological disorders.

Practical Approach to Reporting Based on the International System for Serous Fluid Cytopathology.

The International System for Serous Fluid Cytopathology (TIS) is intended for reporting cytological specimens from serous cavities: pleural, abdominal and pericardial cavities. TIS is being adopted into practice in cytology laboratories worldwide. In this system, there are six diagnostic categories: non-diagnostic, negative for malignancy, atypia of undetermined significance, suspicious for malignancy, malignant-primary and malignant-secondary. Malignant-primary category almost always implies malignant mesothelioma and malignant-secondary usually refers to metastasis from carcinoma but also to involvement of serous cavity by haematolymphoid and other malignancies. When evaluating effusion cytological specimen adequacy, the factors that must be considered are sample volume, cellular content and cellular preservation. In the diagnostic analysis and interpretation, it is helpful to consider systematically all basic cytomorphological components in a sample. The basic components are architecture, cell populations, cell size, cytoplasm, nuclei and background elements. One important requirement for a successful evaluation of an effusion cytological specimen is sufficient clinical and radiological information in a referral. Clinical information may guide ancillary testing. In the present review, we provide a practical and educational approach to reporting serous effusion cytology based on the TIS.

Effect of Fruit and Vegetable Consumption on Human Health: An Update of the Literature

Several meta-analyses have consistently demonstrated that the consumption of an adequate level of fruit and vegetables (F&V), along with other food groups, is associated with a low risk of all-cause mortality, and, as such, represents one of the major modifiable risk factors related to the growing burden of Non-Communicable Diseases (NCDs). The aim of the present narrative review was to provide an up-to-date analysis of systematic reviews and meta-analyses published in the past five years, dealing with the effects of F&V consumption on human health, focusing on specific pathologies, such as total mortality, cancer, cardiovascular diseases (CVDs), type 2 diabetes, intestinal inflammation, and bone and respiratory illnesses. The results of our evaluation confirmed and consolidated the protective role of F&V consumption against the development of NCDs, especially CVDs. However, the need to corroborate existing evidence and clarify the role of confounding factors by performing additional randomized control trials and adopting more standardized approaches and study designs also emerged. Moreover, evaluating the protective role of fruit and vegetables as separate food categories appeared to be one of the most interesting areas to investigate in the near future. Overall, these outcomes could help in addressing future research to better establish a causal relationship between F&V consumption and human health.

Effect of Gestational Diabetes Mellitus on Newborn Hearing: A Systematic Review.

Gestational diabetes mellitus (GDM) is associated with several adverse health conditions in newborns such as preterm birth, hyperbilirubinemia, macrosomia, respiratory distress. However, the effect of GDM on the hearing sensitivity of newborns is still unclear. The study aimed to explore the effect of GDM on newborn hearing. The study aimed to explore the effect of GDM on newborn hearing. A systematic search was conducted using PubMed, Scopus, and CHINAL databases. Keywords like "gestational diabetes," "diabetic pregnancies," "hearing loss," "hearing impairment," and "hearing disorder" were used to form a search string. The Rayyan software was used for screening procedure. The full-length articles were shortlisted, extracted, and appraised. The 7 articles were included in the review. Findings suggest that hearing loss is more prevalent in newborns with GDM pregnancies than in non-GDM pregnancies. In addition, OAE findings were "referred during the first hearing screening of newborns with GDM pregnancies." The refer rate of the first bilateral hearing screening was higher for newborns with GDM pregnancies. Furthermore, children of diabetic pregnancies were found to be at risk of bilateral hearing loss, particularly sensorineural in nature. The present systematic review suggests an association between GDM and a higher refer rate in hearing screening. A multidisciplinary collaboration between gynecologists, pediatricians, and audiologists can smoothen the early detection of hearing loss in newborns with GDM pregnancies, leading to early intervention and better clinical outcomes to improve the quality of life of affected newborns.

Wearable Applicability of Respiratory Airflow Transducers: Current Approaches and Future Directions.

Advanced technologies employed in modern respiratory airflow transducers have exhibited powerful capabilities in accurately measuring respiratory flow under controlled and sedentary conditions, particularly in clinical settings. However, the wearable applicability of these transducers as face-mounted electronics for use in occupational and sporting activities remains unexplored. The present review addresses the critical wearability issue associated with current respiratory airflow transducers, including pneumotachographs, orifice flowmeters, turbine flowmeters, hot wire anemometers, ultrasound flowmeters, and piezoelectric airflow transducers. Furthermore, a comprehensive analysis and comparison of all factors that impact the wearable applicability of respiratory airflow transducers are conducted, considering dynamic accuracy, long-term usability, power consumption, calibration frequency, and cleaning requirements. The findings indicate that the piezoelectric airflow transducer stands out as a more viable option for wearables compared to other devices. We expect that this review will serve as a valuable engineering reference, guiding future research efforts in designing and developing wearable respiratory airflow transducers for ambulatory respiratory flow monitoring.

Reconstruction of deep and perforating corneal defects in dogs-A review (Part II/III): Biomaterials and keratoprosthesis.

The surgical reconstruction of severe corneal ulcers is a common and crucial component of the clinical practice of veterinary ophthalmology. Numerous surgical techniques are used in dogs for corneal reconstruction, and these techniques may be categorized by the material used to repair the corneal lesion. The first part of the present review described procedures that utilize autogenous ocular tissues, homologous donor tissues, and heterologous donor tissues. In this second part of the review, the categories of biomaterials and keratoprosthetics will be summarized. Biomaterials that are reported for use in dogs include amniotic membrane, porcine urinary bladder acellular matrix, porcine small intestinal submucosa, acellular porcine corneal stroma, and other miscellaneous soft tissue and cartilage grafts (e.g., preserved equine renal capsule, autologous omentum, autologous buccal mucosa membrane, bovine pericardium, and homologous peritoneum). Descriptions of keratoprosthesis surgery in dogs are currently limited, but the use of artificial corneal transplants hold promise for dogs with severe, vision-compromising corneal disease that is not amenable to other reconstruction techniques. This review describes the results of experimental studies evaluating these graft materials in dogs, and it will summarize the findings and outcomes of the clinical articles published in each material category. Reporting inconsistencies and areas where additional research is required will be highlighted to help guide future studies in this area. A major aim of this review is to help identify potential subjects that could be evaluated in future investigations and that might lead to refinements in clinical practice.

Could intranasal oxytocin enhance the effects of psychotherapy in individuals with mental disorders? A systematic review and meta-analysis

Interest in the therapeutic potential of oxytocin for the treatment of mental health disorders, especially those involving social dysfunction, has increased considerably in recent years. To date, most studies have only evaluated oxytocin as monotherapy, with highly inconsistent results. A new line of research is exploring the effects of combining oxytocin with psychotherapy. The aim of the present review was to evaluate the therapeutic effects of intranasal oxytocin combined with psychotherapy in individuals with psychiatric disorders. Only randomized clinical trial design was eligible for inclusion. A search of relevant databases yielded 2480 articles published through April 30, 2024. Of these, 13 trials (518 participants) were included in this review and 4 of them in a meta-analysis. The trials evaluated a range of different psychotherapeutic interventions, oxytocin doses, and mental disorders. Overall, the trials suggested that combined treatment reduced negative mental representations, decreased stress, and increased therapeutic alliance. Meta-analysis showed that combined treatment significantly reduced depressive symptoms (d= −1.58, 95 % CI: −3.15 to −0.01). However, the treatment with oxytocin had no significant effects on psychiatric symptoms (d= 0.00, 95 % CI: −0.56–0.57) or social functioning (d = 0.21, 95 % CI: −0.07–0.49). Limitations included the heterogeneity and limited sample sizes of the trials. The findings suggest that the combination of intranasal oxytocin and psychotherapy may be an effective therapeutic approach to reduce depressive symptoms in individuals with mental disorders and may improve retention and therapeutic alliance.

Role of pyruvate kinase M2 in regulating sepsis (Review).

Glycolysis occurs in all living organisms as a form of energy supply. Pyruvate kinase M2 (PKM2) is one of the rate‑limiting enzymes in the glycolytic process. PKM2 is considered to serve an important role in several terminal diseases, including sepsis. However, to the best of our knowledge, the specific mechanistic role of PKM2 in sepsis remains to be systematically summarised. Therefore, the present review aims to summarise the roles of PKM2 in sepsis progression. In addition, potential treatment strategies for patients with sepsis are discussed. The present review hopes to lay the groundwork for studying the role of PKM2 and developing therapeutic strategies against metabolic disorders that occur during sepsis.

Emerging Phytochemicals to Treat Leishmaniasis: A Review of Experimental Studies from 2011 to 2021

: Leishmaniasis is a protozoan disease caused by a parasite from the genus Leishmania. It is known as a neglected tropical disease by WHO and is the second-leading cause of death by parasites after malaria. Chemotherapy is the only effective way to control the disease, but treatment options for leishmaniasis are limited. The majority of the drugs are costly, have serious side effects and necessitate hospitalisation. The lack of an effective vaccine, in addition to the emergence of resistance to currently available drugs, has all been raised as major concerns, especially in endemic areas of developing countries. Phytochemicals might contribute to the development of novel and effective drugs for the treatment of leishmaniasis by providing selectively targeted intervention in parasites. Many phytochemicals (quinones, alkaloids, terpenes, saponins, phenolics) and their derivatives are quite active against diverse groups of pathogens, such as viruses, bacteria, fungi and parasites. To date, many phytochemicals have shown potent anti-leishmanial activity with highly selective mode of action. However, due to a lack of interaction between academician and pharma industries none of them has undergone the clinical assessment. The present review will analyse the most promising phytochemicals and their synthetic compounds, which have shown antileishmal activity in in-vitro and subsequently in animal studies from 2011-2021. These phytochemicals are apigenin, hydroxyflavanone, Epigallocatechin-O-3 gallate, caffeic acid, α-bisabolol, β-caryophyllene, ursolic acid, quinones, which have shown notable anti-leishmanial activities in several independent studies.

Current strategies for nonalcoholic fatty liver disease treatment (Review).

Nonalcoholic fatty liver disease (NAFLD), the most common chronic hepatic disease, has become a leading health problem worldwide. The present review summarized the methods and mechanisms to treat NAFLD, including the Mediterranean diet, physical activity and exercise, bariatric surgery and specific therapeutic agents, including statins, peroxisome proliferator‑activated receptor agonists, cenicriviroc and farnesoid X receptor agonists. Biologically active substances, such as peptides, alkaloids, polyphenolic compounds, silymarin, antibiotics, fatty acids, vitamins, probiotics, synbiotics and lamiaceae have also demonstrated actions that combat NAFLD. Considering their different mechanisms of action, combining some of them may prove an efficacious treatment for NAFLD. In this light, the present review describes recent progress and future prospects in treating NAFLD.

Structural Perspectives in the Development of Novel EGFR Inhibitors for the Treatment of NSCLC.

Non-small cell Lung cancer (NSCLC) is the most common type of lung cancer, which is caused by high consumption of tobacco and smoking. It is an epithelial lung cancer that affects about 2.2 million people across the globe, according to International Agency for Research on Cancer (IARC). Non-small cell lung cancer is a malignant tumor caused by EGFR mutation that occurs in the in-frame deletion of exon 19 and L858R point mutation in exon 21. Presently, clinically available inhibitors of EGFR (including erlotinib, lapatinib, gefitinib, selumetinib, etc.) are not specific and responsible for undesirable adverse effects. Moreover, to solve this problem search for newer EGFR inhibitors is the utmost need for the treatment and/or management of increasing lung cancer burden. The discovery of therapeutic agents that inhibit the specific target in tumorous cells, such as EGFR, is one of the successful strategies in treating many cancer therapies, including lung cancer. The exhaustive literature survey (2018-2023) has shown the importance of medicinally privileged pyrimidine derivatives together, fused and/or clubbed with other heterocyclic rings to design and develop novel EGFR inhibitors. Pyrimidine derivatives substituted with phenylamine, indole, pyrrole, piperazine, pyrazole, thiophene, pyridine and quinazoline derivatives substituted with phenylamine, pyrimidine, morpholine, pyrrole, dioxane, acrylamide, indole, pyridine, furan, pyrimidine, pyrazole etc. are privileged heterocyclic rings shown promising activity by inhibiting EGFR and TKIs. The present review summarizes the structure-activity relationship (SAR) and enzyme inhibitory activity, including IC50 values, percentage inhibition, and kinetic studies of potential compounds from various literature. The review also includes various aspects of molecular docking studies with compounds under clinical trials and patents filed on pyrimidine-based EGFR inhibitors in treating non-small cell lung cancer. The present review may benefit the medicinal chemist for developing novel compounds such as EGFR inhibitors.

A Comprehensive Examination of ChatGPT's Contribution to the Healthcare Sector and Hepatology.

Artificial Intelligence and Natural Language Processing technology have demonstrated significant promise across several domains within the medical and healthcare sectors. This technique has numerous uses in the field of healthcare. One of the primary challenges in implementing ChatGPT in healthcare is the requirement for precise and up-to-date data. In the case of the involvement of sensitive medical information, it is imperative to carefully address concerns regarding privacy and security when using GPT in the healthcare sector. This paper outlines ChatGPT and its relevance in the healthcare industry. It discusses the important aspects of ChatGPT's workflow and highlights the usual features of ChatGPT specifically designed for the healthcare domain. The present review uses the ChatGPT model within the research domain to investigate disorders associated with the hepatic system. This review demonstrates the possible use of ChatGPT in supporting researchers and clinicians in analyzing and interpreting liver-related data, thereby improving disease diagnosis, prognosis, and patient care.

Reconstruction of deep and perforating corneal defects in dogs-A review (Part I/III): Autogenous ocular tissues, donor tissues, and corneal clarity scoring.

Corneal reconstruction is a key part of veterinary ophthalmic practice and numerous reconstructive techniques have been described for use in small animals in the peer-reviewed veterinary literature written in English. Despite the evidence accrued over the last six decades in over 40 clinical articles and numerous other publications on ocular surface health, several key areas require further study. The comparison between studies is difficult due to elements that go beyond common factors, such as the indication for surgery, the reconstructive technique preferred by the surgeon or the availability of reconstructive materials. However, the differences in reporting style adopted by different authors between similar studies and the lack of data found in retrospective studies add to this complexity. The present review is divided into three parts. One covers the use of autologous materials for reconstruction and corneal transplants, as well as corneal clarity. A second part focuses on biomaterials and keratoprosthetics, while the third part focuses on the use of corneal sutures and report of ocular discomfort/pain in the veterinary literature. The review focuses on the main findings of each reconstruction technique. It aims to identify areas where key information about common procedures is missing so that general guidelines may be provided for the planning of patient record keeping and future retrospective or prospective studies, while it also aims to highlight the presence of knowledge gaps that deserve further attention.

Drug resistance and tumor immune microenvironment: An overview of current understandings (Review).

The use of antitumor drugs represents a reliable strategy for cancer therapy. Unfortunately, drug resistance has become increasingly common and contributes to tumor metastasis and local recurrence. The tumor immune microenvironment (TME) consists of immune cells, cytokines and immunomodulators, and collectively they influence the response to treatment. Epigenetic changes including DNA methylation and histone modification, as well as increased drug exportation have been reported to contribute to the development of drug resistance in cancers. In the past few years, the majority of studies on tumors have only focused on the development and progression of a tumor from a mechanistic standpoint; few studies have examined whether the changes in the TME can also affect tumor growth and drug resistance. Recently, emerging evidence have raised more concerns regarding the role of TME in the development of drug resistance. In the present review, it was discussed how the suppressive TME adapts to drug resistance characterized by the cooperation of immune cells, cytokines, immunomodulators, stromal cells and extracellular matrix. Furthermore, it was reviewed how these immunological or metabolic changes alter immuno‑surveillance and thus facilitate tumor drug resistance. In addition, potential targets present in the TME for developing novel therapeutic strategies to improve individualized therapy for cancer treatment were revealed.

Crosstalk of methylation and tamoxifen in breast cancer (Review).

Tamoxifen is a widely used anti‑estrogen drug in the endocrine therapy of breast cancer (BC). It blocks estrogen signaling by competitively binding to estrogen receptor α (ERα), thereby inhibiting the growth of BC cells. However, with the long‑term application of tamoxifen, a subset of patients with BC have shown resistance to tamoxifen, which leads to low overall survival and progression‑free survival. The molecular mechanism of resistance is mainly due to downregulation of ERα expression and abnormal activation of the PI3K/AKT/mTOR signaling pathway. Moreover, the downregulation of targeted gene expression mediated by DNA methylation is an important regulatory mode to control protein expression. In the present review, methylation and tamoxifen are briefly introduced, followed by a focus on the effect of methylation on tamoxifen resistance and sensitivity. Finally, the clinical application of methylation for tamoxifen is described, including its use as a prognostic indicator. Finally, it is hypothesized that when methylation is used in combination with tamoxifen, it could recover the resistance of tamoxifen.

Radiotherapy-associated Sensorineural Hearing Loss in Pediatric Oncology Patients.

During the radiotherapeutic treatment of pediatric oncology patients, they would be at a latent risk of developing ionizing radiation-induced ototoxicity when the cochlea or auditory nerve is located within the radiation field. Sensorineural hearing loss (SNHL) is an irreversible late complication of radiotherapy, and its incidence depends on various factors such as the patient's hearing sensitivity, total radiation dose to the cochlea, radiotherapy fractionation regimen, age and chemoradiation. Importantly, this complication exhibits serious challenges to adult survivors of childhood cancer, as it has been linked to impairments in academic achievement, psychosocial development, independent living skills, and employment in the survivor population. Therefore, early detection and proper management can alleviate academic, speech, language, social, and psychological morbidity arising from hearing deficits. In the present review, we have addressed issues such as underlying mechanisms of radiation-induced SNHL, audiometric findings of pediatric cancer patients treated with radiotherapy, and management and protection measures against radiation-induced ototoxicity.

Therapeutic Potential of Capsaicin in Various Neurodegenerative Diseases with Special Focus on Nrf2 Signaling.

Neurodegenerative disease is mainly characterized by the accumulation of misfolded proteins, contributing to mitochondrial impairments, increased production of proinflammatory cytokines and reactive oxygen species, and neuroinflammation resulting in synaptic loss and neuronal loss. These pathophysiological factors are a serious concern in the treatment of neurodegenerative diseases. Based on the symptoms of various neurodegenerative diseases, different treatments are available, but they have serious side effects and fail in clinical trials, too. Therefore, treatments for neurodegenerative diseases are still a challenge at present. Thus, it is important to study an alternative option. Capsaicin is a naturally occurring alkaloid found in capsicum. Besides the TRPV1 receptor activator in nociception, capsaicin showed a protective effect in brain-related disorders. Capsaicin also reduces the aggregation of misfolded proteins, improves mitochondrial function, and decreases ROS generation. Its antioxidant role is due to increased expression of an nrf2-mediated signaling pathway. Nrf2 is a nuclear erythroid 2-related factor, a transcription factor, which has a crucial role in maintaining the normal function of mitochondria and the cellular defense system against oxidative stress. Intriguingly, Nrf2 mediated pathway improved the upregulation of antioxidant genes and inhibition of microglial-induced inflammation, improved mitochondrial resilience and functions, leading to decreased ROS in neurodegenerative conditions, suggesting that Nrf2 activation could be a better therapeutic approach to target pathophysiology of neurodegenerative disease. Therefore, the present review has evaluated the potential role of capsaicin as a pharmacological agent for the treatment and management of various neurodegenerative diseases via the Nrf2-mediated signaling pathway.