Oxidative stress due to aberrant metabolism is considered as a crucial contributor to diabetes and its complications. Hyperglycemia and hyperlipemia boost excessive reactive oxygen species generation by elevated mitochondrial respiration, increased nicotinamide adenine dinucleotide phosphate oxidase activity, and enhanced pro-oxidative processes, including protein kinase C pathways, hexosamine, polyol, and advanced glycation endproducts, which exacerbate oxidative stress. Oxidative stress plays a significant role in the onset of diabetes and its associated complications by impairing insulin production, increasing insulin resistance, maintaining hyperglycemic memory, and inducing systemic inflammation. A more profound comprehension of the molecular processes that link oxidative stress to diabetes is crucial to new preventive and therapeutic strategies. Therefore, this review discusses the mechanisms underlying how oxidative stress contributes to diabetes mellitus and its complications. We also summarize the current approaches for prevention and treatment by targeting the oxidative stress pathways in diabetes.
Oxidative Stress/physiology* ; Humans ; Diabetes Mellitus/physiopathology* ; Diabetes Complications/metabolism* ; Reactive Oxygen Species/metabolism* ; Glycation End Products, Advanced/metabolism* ; Animals

BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

The construction of"flagship"hospitals of the synergy of Chinese and Western medicine is promoting of quality development of public hospitals and for enhancing the status and effectiveness of integrated Chinese and Western medicines in the treatment of patients.By collecting data from 62"flagship"hospitals in China,it analyzed the current situation of the construction from the aspects of regional layout,practical experience,and practical problems,and proposed the key paths for the future high-quality development of the"flagship"hospitals of the synergy of Chinese and Western medicines in the light of the policy objectives:adhering to the leadership of Party building,constructing the evaluation index system of the"flagship"hospitals of Chinese and Western medicine collaboration,establishing a long-term safeguard mechanism through the collaboration of multiple main bodies,introducing lean management,and promoting the construction of digital intelligence.

The construction of"flagship"hospitals of the synergy of Chinese and Western medicine is promoting of quality development of public hospitals and for enhancing the status and effectiveness of integrated Chinese and Western medicines in the treatment of patients.By collecting data from 62"flagship"hospitals in China,it analyzed the current situation of the construction from the aspects of regional layout,practical experience,and practical problems,and proposed the key paths for the future high-quality development of the"flagship"hospitals of the synergy of Chinese and Western medicines in the light of the policy objectives:adhering to the leadership of Party building,constructing the evaluation index system of the"flagship"hospitals of Chinese and Western medicine collaboration,establishing a long-term safeguard mechanism through the collaboration of multiple main bodies,introducing lean management,and promoting the construction of digital intelligence.

The construction of"flagship"hospitals of the synergy of Chinese and Western medicine is promoting of quality development of public hospitals and for enhancing the status and effectiveness of integrated Chinese and Western medicines in the treatment of patients.By collecting data from 62"flagship"hospitals in China,it analyzed the current situation of the construction from the aspects of regional layout,practical experience,and practical problems,and proposed the key paths for the future high-quality development of the"flagship"hospitals of the synergy of Chinese and Western medicines in the light of the policy objectives:adhering to the leadership of Party building,constructing the evaluation index system of the"flagship"hospitals of Chinese and Western medicine collaboration,establishing a long-term safeguard mechanism through the collaboration of multiple main bodies,introducing lean management,and promoting the construction of digital intelligence.

The construction of"flagship"hospitals of the synergy of Chinese and Western medicine is promoting of quality development of public hospitals and for enhancing the status and effectiveness of integrated Chinese and Western medicines in the treatment of patients.By collecting data from 62"flagship"hospitals in China,it analyzed the current situation of the construction from the aspects of regional layout,practical experience,and practical problems,and proposed the key paths for the future high-quality development of the"flagship"hospitals of the synergy of Chinese and Western medicines in the light of the policy objectives:adhering to the leadership of Party building,constructing the evaluation index system of the"flagship"hospitals of Chinese and Western medicine collaboration,establishing a long-term safeguard mechanism through the collaboration of multiple main bodies,introducing lean management,and promoting the construction of digital intelligence.

The construction of"flagship"hospitals of the synergy of Chinese and Western medicine is promoting of quality development of public hospitals and for enhancing the status and effectiveness of integrated Chinese and Western medicines in the treatment of patients.By collecting data from 62"flagship"hospitals in China,it analyzed the current situation of the construction from the aspects of regional layout,practical experience,and practical problems,and proposed the key paths for the future high-quality development of the"flagship"hospitals of the synergy of Chinese and Western medicines in the light of the policy objectives:adhering to the leadership of Party building,constructing the evaluation index system of the"flagship"hospitals of Chinese and Western medicine collaboration,establishing a long-term safeguard mechanism through the collaboration of multiple main bodies,introducing lean management,and promoting the construction of digital intelligence.

The construction of"flagship"hospitals of the synergy of Chinese and Western medicine is promoting of quality development of public hospitals and for enhancing the status and effectiveness of integrated Chinese and Western medicines in the treatment of patients.By collecting data from 62"flagship"hospitals in China,it analyzed the current situation of the construction from the aspects of regional layout,practical experience,and practical problems,and proposed the key paths for the future high-quality development of the"flagship"hospitals of the synergy of Chinese and Western medicines in the light of the policy objectives:adhering to the leadership of Party building,constructing the evaluation index system of the"flagship"hospitals of Chinese and Western medicine collaboration,establishing a long-term safeguard mechanism through the collaboration of multiple main bodies,introducing lean management,and promoting the construction of digital intelligence.

The construction of"flagship"hospitals of the synergy of Chinese and Western medicine is promoting of quality development of public hospitals and for enhancing the status and effectiveness of integrated Chinese and Western medicines in the treatment of patients.By collecting data from 62"flagship"hospitals in China,it analyzed the current situation of the construction from the aspects of regional layout,practical experience,and practical problems,and proposed the key paths for the future high-quality development of the"flagship"hospitals of the synergy of Chinese and Western medicines in the light of the policy objectives:adhering to the leadership of Party building,constructing the evaluation index system of the"flagship"hospitals of Chinese and Western medicine collaboration,establishing a long-term safeguard mechanism through the collaboration of multiple main bodies,introducing lean management,and promoting the construction of digital intelligence.

The construction of"flagship"hospitals of the synergy of Chinese and Western medicine is promoting of quality development of public hospitals and for enhancing the status and effectiveness of integrated Chinese and Western medicines in the treatment of patients.By collecting data from 62"flagship"hospitals in China,it analyzed the current situation of the construction from the aspects of regional layout,practical experience,and practical problems,and proposed the key paths for the future high-quality development of the"flagship"hospitals of the synergy of Chinese and Western medicines in the light of the policy objectives:adhering to the leadership of Party building,constructing the evaluation index system of the"flagship"hospitals of Chinese and Western medicine collaboration,establishing a long-term safeguard mechanism through the collaboration of multiple main bodies,introducing lean management,and promoting the construction of digital intelligence.