Retracted: Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury.

This publication has been retracted by the Editor due to non-original content and deficiencies in the conduct of the study. Reference: Xiao-Bin Zhang, Gong-Ping Chen, Mao-Hong Huang, Xiang-Xing Chen, Feng-Fu Zhan, Xiu-Zhen He, Ling Cai, Hui-Qing Zeng Med. Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury. Med Sci Monit, 2022; 28: e936760. DOI: 10.12659/MSM.936760.

Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury.

BACKGROUND As a novel pathophysiological characteristic of obstructive sleep apnea, intermittent hypoxia (IH) contributes to human renal tubular epithelial cells impairment. The underlying pathological mechanisms remain unrevealed. The present study aimed to evaluate the influence of Bcl-2 19-kDa interacting protein 3 (BNIP3)-mediated mitophagy on IH-induced renal tubular epithelial cell impairment. MATERIAL AND METHODS Human kidney proximal tubular (HK-2) cells were exposed to IH condition. IH cycles were as follows: 21% oxygen for 25 min, 21% descended to 1% for 35 min, 1% oxygen sustaining for 35 min, and 1% ascended to 21% for 25 min. The IH exposure lasted 24 h with 12 cycles of hypoxia and re-oxygenation. Both the siBNIP3 and BNIP3 vector were transfected to cells. Cell viability and apoptosis, mitochondrial morphology and function, and mitophagy were detected by cell counting kit-8, flow cytometry and TUNEL staining, transmission electron microscopy, western blotting, and immunofluorescence, respectively. RESULTS In the IH-induced HK-2 cells, inhibition of BNIP3 further aggravated mitochondrial structure damage, and decreased mitophagy level, leading to increased cell apoptosis and decreased cell viability. While overexpression of BNIP3 enhanced mitophagy, which protected mitochondrial structure, it can decrease cell death in HK-2 cells exposed to IH. CONCLUSIONS The present study showed that BNIP3-mediated mitophagy plays a protective role against IH-induced renal tubular epithelial cell impairment.

[Advances in clinical prediction scores for prognosis of coronavirus disease-2019].

Coronavirus Disease-2019 (COVID-19) has been a major public health issue all over the world, placing a significant burden on available healthcare resources. The most common types of COVID-19 are the mild and common forms. Although the proportion of the severe-critical types is smaller, the rate of death is significantly higher and the medical resources required tend to be greater. Thus, a variety of scores based on other disease and COVID-19 were used to assess the risk of poor prognosis on the COVID-19, including the common scores for community-acquired pneumonia, sepsis and viral pneumonia. Unfortunately, the above scores often lacked an adequate description of the applicable population or were at high risk of bias with unknown applicability. Therefore, the article summarized the existing scores, aiming to provide a reference for clinical prognostic risk assessment.

UFL1 regulates cellular homeostasis by targeting endoplasmic reticulum and mitochondria in NEFA-stimulated bovine mammary epithelial cells via the IRE1α/XBP1 pathway.

Elevated levels of NEFA caused by negative energy balance in transition cows induce cellular dyshomeostasis. Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1) can maintain cellular homeostasis and act as a critical regulator of stress responses besides functioning in the ubiquitin-like system. The objective of this study was to elucidate the UFL1 working mechanism on promoting cellular adaptations in bovine mammary epithelial cells (BMECs) in response to NEFA challenge, with an emphasis on the ER and mitochondrial function. The results showed that exogenous NEFA and UFL1 depletion resulted in the disorder of ER and mitochondrial homeostasis and the damage of BMEC integrity, overexpression of UFL1 effectively alleviated the NEFA-induced cellular dyshomeostasis. Mechanistically, our study found that UFL1 had a strong interaction with IRE1α and could modulate the IRE1α/XBP1 pathway of unfolded protein response in NEFA-stimulated BMECs, thereby contributing to the modulation of cellular homeostasis. These findings imply that targeting UFL1 may be a therapeutic alternative to relieve NEB-induced metabolic changes in perinatal dairy cows.

H2O2-induced oxidative stress impairs meat quality by inducing apoptosis and autophagy via ROS/NF-κB signaling pathway in broiler thigh muscle.

Oxidative stress is the downstream of various adverse stresses which impairs meat quality of broiler chickens. Yet, the specific molecular mechanisms of oxidative stress in meat quality of broiler thigh muscle remains unclear. This study investigated the effects and mechanisms of H2O2-induced oxidative stress on meat quality of broiler thigh muscle, with particular emphasis on apoptosis and autophagy and the ROS/NF-κB signaling pathway. The results showed that 10%H2O2-treated broilers exhibited significantly higher drip loss and shear force and lower pH24h and muscle weight. Moreover, the ROS formation, the contents of oxidation products, the expressions of caspases (3, 6, 8, 9), Beclin1, and LC3-II/LC3-I were significantly increased, whereas the levels of antioxidation products and the expression of phosphorylation of NF-κBp65 were significantly decreased. These findings from the present study indicating that H2O2-induced oxidative stress significantly impaired the meat quality by inducing apoptosis and abnormal autophagy via ROS/NF-κB signaling pathway in the broiler thigh muscle.

Transcriptome Analysis Reveals That NEFA and ß-Hydroxybutyrate Induce Oxidative Stress and Inflammatory Response in Bovine Mammary Epithelial Cells.

Non-esterified fatty acids (NEFA) and ß-hydroxybutyrate (BHBA) are the metabolites of fat mobilization initiated by negative energy balance (NEB) during the perinatal period in dairy cows, which have an adverse effect on cell physiology of various bovine cell types. The aim of this study was to explore the biological roles of NEFA and BHBA on provoking oxidative stress and inflammatory responses in bovine mammary epithelial cells (BMECs). RNA sequencing analysis showed that there are 1343, 48, and 1725 significantly differentially expressed genes (DEGs) in BMECs treated with NEFA, BHBA and their combination. GO functional analysis revealed that the DEGs were significantly enriched in "response to oxidative stress" and "inflammatory response". Further study demonstrated that NEFA and BHBA elevated the malondialdehyde (MDA) and reactive oxygen species (ROS) accumulation and reduced the total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activity to cause oxidative stress. In addition, expression of inflammatory markers (NO, TNF-α, IL-6, and IL-1ß) were increased after NEFA and BHBA stimulation. Mechanistically, our data showed that NEFA and BHBA activated the MAPK signaling pathway. Collectively, our results indicate that NEFA and BHBA induce oxidative stress and inflammatory response probably via the MAPK signaling pathway in BMECs.

Dietary taurine attenuates hydrogen peroxide-impaired growth performance and meat quality of broilers via modulating redox status and cell death signaling.

Oxidative stress seriously affects poultry production. Nutritional manipulations have been effectively used to alleviate the negative effects caused by oxidative stress. This study investigated the attenuating effects and potential mechanisms of dietary taurine on the growth performance and meat quality of broiler chickens challenged with hydrogen peroxide (H2O2). Briefly, a total of 192 male Arbor Acres broilers (28 d old) were randomly categorized into three groups: non-injection of birds on basal diets (control), 10.0% H2O2 injection of birds on basal diets (H2O2), and 10.0% H2O2 injection of birds on basal diets supplemented with 5 g/kg taurine (H2O2 + taurine). Each group consisted of eight cages of eight birds per cage. Results indicated that H2O2 administration significantly reduced growth performance and impaired breast meat quality by decreasing ultimate pH and increasing shear force value (P < 0.05). Dietary taurine improved the body weight gain and feed intake and decreased feed/gain ratio of H2O2-challenged broilers. Meanwhile, oxidative stress induced by intraperitoneal injection of H2O2 suppressed the nuclear factor-κB (NF-κB) signaling and initiated autophagy and apoptosis. Compared with the H2O2 group, taurine supplementation restored the redox status in the breast muscle by decreasing levels of reactive oxygen species and contents of oxidative products and increasing antioxidant capacity (P < 0.05). Moreover, upregulated mRNA expression of NF-κB signaling-related genes, including NF-κB subunit 1 (p50) and B-cell CLL/lymphoma 2 (Bcl-2), and enhanced protein expression of NF-κB were observed in the H2O2 + taurine group (P < 0.05). Additionally, dietary taurine decreased the expression of caspase family, beclin1, and microtubule-associated protein 1light chain 3 beta (LC3-II; P < 0.05), thereby rescuing autophagy and apoptosis in breast muscle induced by H2O2. Collectively, dietary supplementation with taurine effectively improves growth performance and breast meat quality of broilers challenged with H2O2, possibly by protecting against oxidative injury and modulating cell death signaling.

Hydrogen Peroxide-Induced Change in Meat Quality of the Breast Muscle of Broilers Is Mediated by ROS Generation, Apoptosis, and Autophagy in the NF-κB Signal Pathway.

We investigated the relationship between meat quality and oxidative damage caused by hydrogen peroxide (H2O2) in the breast muscle of broilers. Moreover, we explored the occurrence of apoptosis and autophagy, as well as the expression of NF-κB in these signaling pathways to provide evidence of possible oxidative damage mechanisms. The broilers received a basal diet and were randomly divided into five treatments (noninjected control, 0.75% saline-injected, and 2.5%, 5.0%, or 10.0% H2O2-injected treatments; 1.0 mL/kg in body weight). The results showed that oxidative stress induced by H2O2 had a negative effect on relative muscle weight, histomorphology, and redox status, while the underlying oxidative damage caused a decline in meat quality (decrease of pH24h, 10% H2O2 treatment; increase of shear force, 5% and 10% H2O2 treatments) of broilers. This could be attributed to the apoptosis and autophagy processes triggered by excessive reactive oxygen species that suppress the NF-κB signaling pathway.

Preslaughter Transport Effect on Broiler Meat Quality and Post-mortem Glycolysis Metabolism of Muscles with Different Fiber Types.

Preslaughter transport has been reported to decrease the quality of breast meat but not thigh meat of broilers. However, tissue-specific difference in glycogen metabolism between breast and thigh muscles of transported broilers has not been well studied. We thus investigated the differences in meat quality, adenosine phosphates, glycolysis, and bound key enzymes associated with glycolysis metabolism in skeletal muscles with different fiber types of preslaughter transported broilers during summer. Compared to a 0.5 h transport, a 3 h transport during summer decreased ATP content, increased AMP content and AMP/ATP ratio, and accelerated glycolysis metabolism via the upregulation of glycogen phosphorylase expression accompanied by increased activities of bound glycolytic enzymes (hexokinase, pyruvate kinase, and lactate dehydrogenase) in pectoralis major muscle, which subsequently increased the likelihood of pale, soft, and exudative-like breast meat. On the other hand, a 3 h transport induced only a moderate glycolysis metabolism in tibialis anterior muscle, which did not cause any noticeable changes in the quality traits of the thigh meat.