Corrigendum: Nanofat lysate ameliorates pain and cartilage degradation of osteoarthritis through activation of TGF-ß-Smad2/3 signaling of chondrocytes.

[This corrects the article DOI: 10.3389/fphar.2023.900205.].

α-ketoglutarate preconditioning extends the survival of engrafted adipose-derived mesenchymal stem cells to accelerate healing of burn wounds.

The application of adipose-derived stem cells (ADSCs) in treating hard-to-heal wounds has been widely accepted, while the short-term survival rate remains an obstacle in stem cell therapy. The aim of this study is to investigate the effect of preconditioning ADSCs with α-ketoglutarate (α-KG) on the healing of acid burn wounds and cell survival within wounds. Preconditioning of ADSCs was performed by treating cells at passage 3 with 3.5 mM DM-αKG for 24 h. Proliferation and migration of ADSCs was examined. An acid burn wound was created on the dorsal skin of mice. Cell suspension of ADSCs (2 × 106 cells/ml), either pre-treated with α-KG or not, was injected subcutaneously around the margin of wound. At 1,4,7,10,14 days after injection, the percentage of wound closure was evaluated. Expression of pro-angiogenic factors, matrix molecules and HIF1-α in pretreated ADSCs or in wounds was evaluated by qRT-PCR and immunohistochemistry staining, respectively. The survival rate of DiO-labelled ADSCs was determined with the in vivo bioluminescent imaging system. Treating with α-KG induced an enhancement in migration of ADSCs, while their proliferation was not affected. Expression of Vegf and Fgf-2 was significantly increased. With injection of pretreated ADSCs, healing of wounds was remarkably accelerated, along with increased ECM deposition and microvessel density. Moreover, pretreatment with α-KG resulted a prolonged survival of engrafted ADSCs was observed. Expression of HIF-1α was significantly increased in ADSCs treated with α-KG and in wounds injected with preconditioned ADSCs. Our results revealed that healing of acid burn wound was accelerated with administration of ADSCs pretreated with α-KG, which induced elevated expression of HIF-1α and prolonged survival of engrafted stem cells.

Ferrostatin-1 Reversed Chronic Intermittent Hypoxia-Induced Ferroptosis in Aortic Endothelial Cells via Reprogramming Mitochondrial Function.

Purpose: Chronic intermittent hypoxia (CIH) related arterial endothelium injury is a common cause of cardiovascular system injury. However, the mechanism still needs to be clarified. In this study, we aimed to clarify the role and mechanism of ferrostatin-1 (Fer-1) in CIH-related rat arterial endothelial cells (ROAEC) ferroptosis. Methods: ROAEC was divided into control group, CIH group, and CIH+ Fer-1 group. Cell viability was detected by cell counting kit 8 kits (CCK8). The apoptotic rate, reactive oxygen species (ROS) levels, Fe2+ levels, and lipid ROS levels were detected by flow cytometry. Malondialdehyde (MDA) levels and nicotinamide adenine dinucleotide (NAD+)/NADH ratio were detected via Elisa kits. The mRNA and protein levels of cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were detected by qRT-PCR and Western blot. Mitochondrial structure and function were observed by transmission electron microscope (TEM) and mitochondrial membrane potential (MMP). Central carbon metabolism was measured to compare metabolites among each group. Results: After the CIH exposure, ROAEC cell viability decreased; The levels of cell apoptosis, ROS, Fe2+, MDA, and lip ROS increased; The levels of NAD+/NADP ratio decreased; The mRNA and protein levels of GPX4 and SLC7A11 decreased (all p<0.05). Co-cultured with Fer-1 reversed the levels of apoptosis rate, cell viability, ROS, Fe2+, MAD, lipid ROS, NAD+/NADH ratio and the mRNA and protein expression of GPX4 and SLC7A11 (all p<0.05). The TEM results showed that damaged mitochondrial membrane and the matrix spillover in the CIH group. The results of the JC-1 assay showed decreased MMP in the CIH group. Fer-1 treatment ameliorated the mitochondrial injury. The results of central carbon metabolism found that CIH altered the metabolites in the TCA cycle, which were reversed by Fer-1 treatment. Conclusion: CIH-induced ferroptosis in ROAEC, which were reversed by Fer-1 via reprogramming mitochondrial function.

Circular RNA_0025843 Alleviated Cigarette Smoke Extract Induced Bronchoalveolar Epithelial Cells Ferroptosis.

Purpose: Circular RNA (circRNA) plays an important role in various biological processes. However, their functions in cigarette smoke extract (CSE) induced human normal lung epithelial cells (BEAS-2B) injury remain vague. The study aimed to explore circRNA expression profiles and reveal their potential roles in CSE-treated BEAS-2B cells. Methods: 5% CSE exposure for 24 hours were used to build the BEAS-2B cells ferroptosis model. Differentially expressed circRNAs (DECs) were identified by next-generation RNA sequencing. Six randomly selected DECs were validated via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis were conducted to clarify the potential functions of the DECs. Furthermore, the role of hsa_circ_0025843 in CSE-related BEAS-2B cells ferroptosis was confirmed. Results: 5% CSE exposure induced BEAS-2B cells ferroptosis. Fifty-one up-regulated cirRNAs and 80 down-regulated circRNAs were revealed in CSE-treated BEAS-2B cells. Hsa_circ_0003461, hsa_circ_0007548, hsa_circ_0025843, hsa_circ_0068896, hsa_circ_0005832, and hsa_circ_0053378 were selected randomly to validate the reliability of next-generation RNA sequencing by qRT-PCR. After KEGG pathway analysis, DECs were found to participate in the process of EGFR tyrosine kinase inhibitor resistance and glycerophospholipid metabolism. The knockdown of hsa_circ_0025843 significantly alleviated CSE-induced BEAS-2B cells ferroptosis. Conclusion: The study indicated the circRNA expression profiles in CSE-treated BEAS-2B cells. Hsa_circ_0025843 alleviated CSE induced BEAS-2B cells ferroptosis, which might be a potential therapeutic target of CSE related lung injury.

Complete coding genome sequence of a Teschovirus A genotype strain.

This study reports the complete coding genome sequence of a novel Teschovirus A genotype strain, SG2, isolated from the fecal sample of an infected indigenous pig in western Jiangxi, China.

The role of exosomal circular RNA ZNF292 in intermittent hypoxia-induced AC16 cardiomyocytes injury.

BACKGROUND: Exosomes are involved in cell-to-cell communication in numerous diseases including cardiovascular diseases, neurological diseases. Little attention has been dedicated to exosomal circular RNAs in obstructive sleep apnea (OSA)-related cardiovascular diseases. The aim of this study was to explore the role of exosomal circular RNA ZNF292 (circZNF292) on AC16 cells exposure to intermittent hypoxia (IH). METHODS: Exosome release inhibitor GW4869 was used to examine the effect of exosomes on IH-induced AC16 cells apoptosis. The expression of exosomal circZNF292 was detected by qRT-PCR in AC16 cells exposure to IH, and a luciferase reporter assay was conducted to confirm the connection between circZNF292 and miR-146a-5p. Exosomal circZNF292 was stably transfected with short hairpin RNAs (shRNAs) against circZNF292 and co-cultured with AC16 cells. The expression of miR-146a-5p and apoptosis-related protein was then measured to evaluate the effect of exosomal circZNF292. RESULTS: We found that IH contributed to the AC16 cells apoptosis, and the administration of GW4869 increased the apoptosis of cardiomyocytes when exposed to IH. The expression of exosomal circZNF292 decreased and miR-146a-5p increased significantly in AC16 cells exposed to IH compared to normoxic conditions. Bioinformatics analysis predicted a circZNF292/miR-146a-5p axis in IH-induced cardiomyocytes apoptosis. The dual-luciferase reporter system validated the direct interaction of circZNF292 and miR-146a-5p. Knockdown of circZNF292 increased the expressions of miR-146a-5p and accelerated the AC16 cardiomyocytes apoptosis. CONCLUSIONS: The findings of this study suggested a novel mechanism by which exosomes transmit intrinsic regulatory signals to the myocardium through the exosomal circZNF292/miR-146a-5p axis. This finding highlights the potential of targeting this pathway as a therapeutic approach for treating cardiovascular diseases associated with OSA.

Minimally Invasive Treatment of Inversion Shortening Calcaneal Fractures in the "Out-In" Position.

OBJECTIVE: Heel fractures need extensive surgical incisions and are challenging to successfully reposition using traditional prying. The goal of this study is to evaluate the clinical effectiveness of using a Kirschner pin-guided distractor to treat inversion shortening calcaneal fractures in the "out-in" position. METHODS: A total of 40 data from 37 patients with inversion shortened calcaneal fractures from January 2018 to March 2020 were reviewed. Preoperative lateral and axial X-rays and 3D CT were taken to assess the fracture type, and minimally invasive internal fixation was performed in the "out-in" position with distractor repositioning, and intraoperative and postoperative images were taken to assess fracture repositioning and fixation. During the follow-up period, the postoperative functional recovery status was assessed using the VAS score, AOFAS score, and FAOS score. Paired-samples t-test was used for all data comparisons. RESULTS: All cases received a mean follow-up of 28.49 ± 3.25 months, and the mean fracture healing time was 7.84 ± 0.71 weeks. The postoperative images showed well-fixed fracture repositioning, and calcaneal height, length, width, and inversion angles were significantly improved. At the final follow-up, the calcaneal height, length, and width recovered from 39.35 ± 4.44mm, 79.35 ± 2.7mm, and 45.75 ± 2.87mm preoperatively to 50.93 ± 3.18mm, 82.23 ± 1.90mm, and 39.67 ± 1.58mm postoperatively (p < 0.001; p < 0.001; p < 0.001). The calcaneus inversion angle restored from 7.73° ± 2.26° to 3.80° ± 1.80° (p < 0.001). Böhler's angle and Gissane's angle improved from 13.13° ± 3.02° and 105.15° ± 8.94° to 27.95° ± 3.41° and 122.85° ± 5.54° (p < 0.001; p < 0.001). No non-healing fractures, osteomyelitis, or traumatic arthritis were observed. CONCLUSION: Minimally invasive internal fixation with distractor repositioning in the "out-in" position is effective in the treatment of inversion shortening calcaneal fractures while restoring the anatomy and protecting the soft tissue.

A Novel Platform of MOF for Sonodynamic Therapy Advanced Therapies.

Metal-organic frameworks (MOFs) combined with sonodynamic therapy (SDT) have been introduced as a new and efficient treatment method. The critical advantage of SDT is its ability to penetrate deep tissues and concentrate energy on the tumor site to achieve a non-invasive or minimally invasive effect. Using a sonosensitizer to generate reactive oxygen species (ROS) under ultrasound is the primary SDT-related method of killing tumor cells. In the presence of a sonosensitizer, SDT exhibits a more lethal effect on tumors. The fast development of micro/nanotechnology has effectively improved the efficiency of SDT, and MOFs have been broadly evaluated in SDT due to their easy synthesis, easy surface functionalization, high porosity, and high biocompatibility. This article reviews the main mechanism of action of sonodynamic therapy in cancer treatment, and also reviews the applications of MOFs in recent years. The application of MOFs in sonodynamic therapy can effectively improve the targeting ability of SDT and the conversion ability of reactive oxygen species, thus improving their killing ability on cancer cells. This provides new ideas for the application of micro/nano particles in SDT and cancer therapy.

Surgical treatment of specific Unified Classification System B fractures: potentially destabilising lesser trochanter periprosthetic fractures.

To investigate the clinical effects of specific Unified Classification System B (UCS B)-lesser trochanter periprosthetic fractures and determine whether they occur only with non-cemented stems. A retrospective analysis of 28 patients with specific UCS B2 fractures who underwent two surgical treatments, longer stem revision and internal fixation (LSRIF) and open reduction and internal fixation (ORIF), was performed. The patients were assessed at 1, 3, 6, 12, and 24 months and annually thereafter. Fracture healing, complications, Harris Hip Score (HHS), and the Short Form Health Survey questionnaire (SF-36) quality of life score were assessed at each follow-up. At the time of the last follow-up, seven patients had been lost: three were lost to contact, two died, and two were hospitalised elsewhere and unavailable for follow-up. The remaining 21 patients were followed for an average of 49.3 ± 15.4 (range: 24-74.4) months. Their average fracture healing time was 13.5 ± 1.1 (12-15.4) weeks. Complications included three cases (10.71%) of thrombus, one (3.57%) of heart failure, and one (3.57%) of pulmonary infection. There were no revisions due to prosthesis loosening, subsidence, or infection. At the last follow-up, the HHS, SF-36 mental score, and SF-36 physical score were recorded, LSRIF vs. ORIF (82.9 ± 6.6 vs. 74.7 ± 3.9, p = 0.059; 50.9 ± 7.6 vs. 38 ± 1.4, p = 0.012, and 51.7 ± 8.4 vs. 39.7 ± 3.4, p = 0.032, respectively). Specific UCS B2 fractures mostly occur with non-cemented stems. LSRIF with cables is the main treatment, while ORIF is an option for those elderly in poor condition.

Reverse traction with Kirschner wires and bilateral external fixation device combined with minimally invasive plate oseoynthesis technique for tibial plateau fractures of type Schatzker V and VI.

PURPOSE: Complex bicondylar tibial plateau fracture (TPF) has always been a tricky problem for surgeons. We created a novel external device used intraoperatively consisting of Kirschner wires, and combined with minimally invasive plate oseoynthesis (MIPO) technique to treat complex bicondylar TPFs, and the clinical effect and feasibility were further evaluated. METHODS: From March 2016 to February 2021, 49 cases (29 males and 20 females) were identified as bicondylar TPF, the mean age 47.2 (27-69). All patients adopted the device and MIPO technique. A series of score, complications, and radiographs in the follow-up period, from three months, six months, one year, and two years and the last follow-up, were recorded, from visual analogue score (VAS), hospital for special surgery (HSS), and Short-Form 36 (SF-36), containing physical (PCS) and mental (MCS), and Rasmussen score. RESULTS: Forty-seven patients showed good functional recovery. No patients were lost, mean follow-up time was 28.17 ± 2.81 (24.2-35.4) months. Operation time was 89.80 ± 13.46 (58-110) min. At the last follow-up, VAS was 1.3 ± 0.92 (0-4), HHS was 93.10 ± 2.63 (89-99), PCS was 49.20 ± 7.40 (38-65), and MCS was 50.08 ± 4.77 (43-62). Complications were as follows: cutaneous necrosis (3, 6%), asymptomatic arthritis (3, 6%), symptomatic arthritis (1, 2%), and deep venous thrombosis (1, 2%). Mean fracture healing time was 11.82 ± 1.5 (10-15.4) weeks. All patients got recovery without extra surgery and removed the implants at 12.85 ± 0.76 (11.2-15.4) months. CONCLUSION: Temporary traction device of bilateral external fixator combined with MIPO technique was simple and convenient, with a smaller soft-tissue damage, an easier operational approach, and its worth being promoted.

Metal-organic frameworks (MOFs) as apt luminescent probes for the detection of biochemical analytes.

The detection of active substances in the body is very important for good human health as it gives important insights into the smooth functioning of the body. Most of the conventional materials that can be used as suitable probes require complicated fabrication methodologies, have poor stability and are susceptible to environmental effects. In contrast, metal-organic frameworks (MOFs) offer unique advantages as probes for testing analytes due to their tunable porosity, good specific surface area and ease of modification. Unlike previously reported perspectives/reviews, this perspective focuses on the latest applications of MOFs as detection materials for hydrogen peroxide, various metal ions, hydrogen sulfide, organic small molecules, glutathione, and organic macromolecules such as nucleic acids, and focuses on providing a more detailed mechanism of action. Also, the basic principles of action utilized by this class of materials are discussed.

Detrimental alteration of mesenchymal stem cells by an articular inflammatory microenvironment results in deterioration of osteoarthritis.

BACKGROUND: Articular injection of mesenchymal stem cells (MSCs) has been applied to treat knee osteoarthritis (kOA), but its clinical outcomes are controversial. This study investigated whether an articular inflammatory microenvironment (AIM) impacts MSC-based therapy in a rat model of kOA. METHODS: The biological change of MSCs and the functional change of MSCs on chondrocytes were evaluated under AIM. The key mediator and mechanism for the AIM impact on MSC therapy were explored via gain- and loss-of-function approaches. RESULTS: The results showed that MSCs exerted potent anti-kOA effects in vivo and in vitro, but that this therapy become chondrodestructive if a chronic AIM was present. Mechanistically, the overexpression of MMP13 in the injected MSCs via a MAPKs-AP1 signaling axis was revealed as the underlying mechanism for the detriment outcome. CONCLUSIONS: This study thus clarifies recent clinical findings while also suggesting a means to overcome any detrimental effects of MSC-based therapy while improving its efficacy.

Early surgical treatment of closed reduction and internal fixation for a 30-day old intertrochanteric fracture with hemiplegia after acute stroke: A case report.

RATIONALE: Currently, there are no clear guidelines to determine whether and when to perform surgical hip repair in patients with acute stroke and hip fracture. PATIENT CONCERNS: In this case report, we report a case of 75-year-old woman admitted with left hip pain and limited mobility for 1 month. DIAGNOSES: Patient had a history of acute cerebral infarction 42 days ago, and diagnosed with a left intertrochanteric fracture at another hospital 30 days ago. INTERVENTION: Patient was treated with closed reduction and internal fixation with proximal femoral nail anti-rotation. OUTCOMES: At 2-year follow-up, the patient's basic function was restored. The fracture healed well, and the Harris hip score was 75. LESSONS: Without consistent guidelines, individualized treatment strategies including surgical methods and timing of surgery should be made to weigh the risks and benefits for patients with acute stroke and intertrochanteric fractures.

Clinical Outcomes of Closed Reduction and External Fixation for Isolated Second Metacarpal Base Fracture-Dislocations.

OBJECTIVE: The isolated second metacarpal base fracture-dislocations in adults are rare, and the traditional main treatments include closed reduction with the plaster or splint and open reduction with internal fixation (ORIF). However, closed reduction with the plaster or splint is not solid enough and ORIF can damage the surrounding important tissues. The purpose of this study was to explore the clinical outcomes of closed reduction and external fixation (CREF) for the treatment of isolated second metacarpal base fracture-dislocations. METHODS: Ten patients who suffered isolated second metacarpal base fracture-dislocations between January 1, 2010, and February 1, 2020, were reviewed. All of the patients were treated by CREF. Radiographs and computed tomography scans were performed regularly after the operation. The grip and pinch strength, visual analog scale (VAS) pain score, American Society for Surgery of the Hand total active movement (TAM) and total active flexion (TAF) scores, Cooney score, Sollerman hand function test (SHFT) score, QuickDASH score, and range of motion of the index finger were recorded at the last follow-up visit to evaluate functional recovery; the injured and healthy hands were compared and we also recorded postoperative complications. The paired samples t-test was used to compare the healthy and injured sides. RESULTS: The patients were followed up for a median of 29.50 ± 4.2 months. There were no significant differences in the grip strength, pinch strength, angle of proximal interphalangeal joint (PIPJ) flexion, or angle of distal interphalangeal joint (DIPJ) flexion between the injured and healthy sides at the final follow-up visit (all p > 0.05). The mean TAM (268.20 ± 4.21) and TAF scores (270.60 ± 4.17) on injured side were significantly lower than those on healthy side (all p < 0.05). The mean Cooney score (93.50 ± 7.47) and SHFT score (78.50 ± 1.08) on injured side were lower, while the mean QuickDASH score (7.05 ± 3.11) on injured side was higher than those on healthy side (all p < 0.05). The mean VAS pain score was 0.50 ± 0.53 on injured side. There were no significant postoperative complications except for traumatic arthritis in one patient without obvious clinical symptoms. CONCLUSION: CREF achieves the satisfactory curative effect, and the patients obtain the good functional recovery without significant postoperative complications. CREF is a safe and effective treatment for isolated second metacarpal base fracture-dislocations with satisfactory clinical outcomes.

Nanofat lysate ameliorates pain and cartilage degradation of osteoarthritis through activation of TGF-ß-Smad2/3 signaling of chondrocytes.

Introduction: Nanofat is an effective cell therapy for osteoarthritis (OA). However, it has clinical limitations due to its short half-life. We developed Nanofat lysate (NFL) to overcome the defect of Nanofat and explore its anti-OA efficacy and mechanism. Methods: Monoiodoacetate (MIA) was employed to establish rat OA model. For pain assessment, paw withdrawal latency (PWL) and thermal withdrawal latency (TWL) were evaluated. Degeneration of cartilage was observed by histopathological and immunohistochemical examination. Primary chondrocytes were treated with TNF-α to establish the cellular model of OA. MTT, wound healing, and transwell assays were performed to assess effects of NFL on chondrocytes. RNA-seq, qPCR and Western blot assays were conducted to clarify the mechanism of NFL. Results and Discussion: The animal data showed that PWL and TWL values, Mankin's and OARSI scorings, and the Col2 expression in cartilage were significantly improved in the NFL-treated OA rats. The cellular data showed that NFL significantly improved the proliferation, wound healing, and migration of chondrocytes. The molecular data showed that NFL significantly restored the TNF-α-altered anabolic markers (Sox9, Col2 and ACAN) and catabolic markers (IL6 and Mmp13). The RNA-seq identified that TGF-ß-Smad2/3 signaling pathway mediated the efficacy of NFL, which was verified by qPCR and Western blot that NFL significantly restored the abnormal expressions of TGFßR2, phosphorylated-Smad2, phosphorylated-Smad2/3, Col2, Mmp13 and Mmp3. After long-term storage, NFL exerted similar effects as its fresh type, indicating its advantage of storability. In sum, NFL was developed as a new therapeutic approach and its anti-OA efficacy and mechanism that mediated by TGF-ß-Smad2/3 signaling was determined for the first time. Besides, the storability of NFL provided a substantial advantage than other living cell-based therapies.

Model-based risk assessment of dengue fever transmission in Xiamen City, China.

Background: Quantitative assessment of the risk of local transmission from imported dengue cases makes a great challenge to the development of public health in China. The purpose of this study is to observe the risk of mosquito-borne transmission in Xiamen City through ecological and insecticide resistance monitoring. Quantitative evaluation of mosquito insecticide resistance, community population and the number of imported cases affecting the transmission of dengue fever (DF) in Xiamen was carried out based on transmission dynamics model, so as to reveal the correlation between key risk factors and DF transmission. Methods: Based on the dynamics model and combined with the epidemiological characteristics of DF in Xiamen City, a transmission dynamics model was built to simulate the secondary cases caused by imported cases to evaluate the transmission risk of DF, and to explore the influence of mosquito insecticide resistance, community population and imported cases on the epidemic situation of DF in Xiamen City. Results: For the transmission model of DF, when the community population is between 10,000 and 25,000, changing the number of imported DF cases and the mortality rate of mosquitoes will have an impact on the spread of indigenous DF cases, however, changing the birth rate of mosquitoes did not gain more effect on the spread of local DF transmission. Conclusions: Through the quantitative evaluation of the model, this study determined that the mosquito resistance index has an important influence on the local transmission of dengue fever caused by imported cases in Xiamen, and the Brayton index can also affect the local transmission of the disease.

Nrf2 plays protective role during intermittent hypoxia-induced ferroptosis in rat liver (BRL-3A) cells.

PURPOSE: Ferroptosis is reported to be involved in the chronic intermittent hypoxia (CIH)-related liver damage in vivo. Nuclear factor E2-related factor 2 (Nrf2) has an essential role in the regulation of ferroptosis. This study tested the hypothesis that intermittent hypoxia (IH) could lead to hepatocyte ferroptosis in vitro and the function of Nrf2 in IH-induced hepatocyte ferroptosis. METHODS: BRL-3A cells (rat liver cells) were exposed to normoxia or IH. The protocol of IH consisted of 32 cycles of 60-min hypoxic exposure with 30-min reoxygenation phase (nadir of 1% oxygen to peak of 20% oxygen). Ferroptosis was evaluated by cell viability, iron concentration, lipid reactive oxygen species (ROS), protein content of ferritin heavy chain (FTH1), and glutathione peroxidase 4 (GPX4). Both ferrostatin-1 (a ferroptosis inhibitor) and Nrf2 interfering RNA were applied to treat BRL-3A cells, respectively. RESULTS: IH exposure induced ferroptosis in BRL-3A cells with decreased cell viability and increased total iron content and lipid ROS levels. The protein contents of GPX4 and FTH1 in IH group were markedly lower than that in normoxic control. Ferroptosis inhibitor ferrostatin-1 alleviated IH-induced ferroptosis in BRL-3A cells. IH treatment enhanced expression of Nrf2, and Nrf2 knockdown augmented IH-induced ferroptosis in BRL-3A cells. CONCLUSIONS: The results revealed that Nrf2 played a protective role during IH-induced ferroptosis in BRL-3A cells. The finding provides a therapeutic target for obstructive sleep apnea-related liver injury.

Association Between Metabolic-Associated Fatty Liver Disease and Obstructive Sleep Apnea: A Cross-Sectional Study.

Aim: Emerging evidence has revealed that obstructive sleep apnea (OSA) is an independent risk factor for the development of a variety of adverse metabolic disease states. In this study, we evaluated the association between OSA severity and metabolic dysfunction-associated fatty liver disease (MAFLD) among Asian populations. Materials and Methods: This was a cross-sectional, single-center study. The study cohort consisted of patients undergoing polysomnography and abdominal ultrasonography. Logistic regression analysis was used to evaluate the independent risk factors of MAFLD in patients with OSA. Results: A total of 1065 patients (277 non-MAFLD and 788 MAFLD) were included in the study. The prevalence of MAFLD in non-OSA, mild-moderate OSA, and severe OSA patients was 58.16%, 72.41%, and 78.0%, respectively (p < 0.001). We identified significant differences in body mass index (BMI), apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and lowest O2 saturation (LaSO2) between non-MAFLD and MAFLD patients (all p < 0.001). After adjusting for confounding variables, we used multivariate regression analysis to show that BMI, ODI, and triglyceride (TG) levels independently predicted the occurrence of MAFLD (odds ratio [OR] = 1.234, p < 0.001; OR = 1.022, p = 0.013; OR = 1.384, p = 0.001, respectively). Moreover, stratified analysis according to BMI indicated that TG levels were the predominant risk factor for MAFLD in a group of patients with a BMI < 23 kg/m2, while BMI, ODI, TG levels, and total cholesterol (TC) were the major risk factors for MAFLD in a group of patients with a BMI ≥ 23 kg/m2 (all p < 0.05). Conclusion: OSA-associated chronic intermittent hypoxia was independently associated with the risk of MAFLD, especially in OSA patients with a BMI ≥ 23 kg/m2, suggesting that oxidative stress might play an important role in the pathogenesis of MAFLD in patients with OSA.