Pomegranate polyphenol punicalagin as a nutraceutical for mitigating mild cognitive impairment: An overview of beneficial properties.

Dementia treatment has become a global research priority, driven by the increase in the aging population. Punicalagin, the primary polyphenol found in pomegranate fruit, exhibits a variety of benefits. Today, a growing body of research is showing that punicalagin is a nutraceutical for the prevention of mild cognitive impairment (MCI). However, a comprehensive review is still lacking. The aim of this paper is to provide a comprehensive review of the physicochemical properties, origin and pharmacokinetics of punicalagin, while emphasizing the significance and mechanisms of its potential role in the prevention and treatment of MCI. Preclinical and clinical studies have demonstrated that Punicalagin possesses the potential to effectively target and enhance the treatment of MCI. Potential mechanisms by which punicalagin alleviates MCI include antioxidative damage, anti-neuroinflammation, promotion of neurogenesis, and modulation of neurotransmitter interactions. Overall, punicalagin is safer and shows potential as a therapeutic compound for the prevention and treatment of MCI, although more rigorous randomized controlled trials involving large populations are required.

Vertically spliced tabletop light field cave display with extended depth content and separately optimized compound lens array.

Tabletop three-dimensional light field display is a kind of compelling display technology that can simultaneously provide stereoscopic vision for multiple viewers surrounding the lateral side of the device. However, if the flat panel light field display device is simply placed horizontally and displayed directly above, the visual frustum will be tilted and the 3D content outside the display panel will be invisible, the large oblique viewing angle will also lead to serious aberrations. In this paper, we demonstrate what we believe to be a new vertical spliced light field cave display system with an extended depth content. A separate optimization of different compound lens array attenuates the aberration from different oblique viewing angles, and a local heating fitting method is implemented to ensure the accuracy of fabrication process. The image coding method and the correction of the multiple viewpoints realize the correct construction of spliced voxels. In the experiment, a high-definition and precisely spliced 3D city terrain scene is demonstrated on the prototype with a correct oblique perspective in 100-degree horizontal viewing range. We envision that our research will provide more inspiration for future immersive large-scale glass-free virtual reality display technologies.

Lumen-apposing metal stents versus traditional self-expanding metal stents for endoscopic ultrasound-guided drainage of pancreatic fluid collections: a systematic review and meta-analysis.

BACKGROUND: Endoscopic drainage has become the preferred treatment for pancreatic fluid collections (PFCs). There is still a lack of reliable evidence to prove which metal stent is the best choice for endoscopic ultrasound (EUS)-guided drainage of PFCs. In this study, we aimed to evaluate the efficacy and safety of lumen-apposing metal stents (LAMS) compared to traditional self-expanding metal stents (SEMS) in meta-analysis. METHODS: We systematically searched PubMed, Embase, Web of Science, and Cochrane Library up to July 15, 2023. Relevant publications that compared LAMS with traditional SEMS for drainage of patients' PFCs under EUS-guidance were included. This meta-analysis assessed endpoints using Review Manager 5.3 and Stata 14.0 statistical software. RESULT: Nine citations comprising 707 patients with PFCs were included. The clinical success rate of LAMS tended to be higher than that of SEMS (RR = 1.07, 95%CI [1.00, 1.15], P = 0.05). LAMS had a lower technical success rate (RR = 0.97, 95%CI [0.94, 0.99], P = 0.02) and faster procedure time (minutes) (MD = - 24.29, 95%CI [- 25.59, - 22.99], P < 0.00001) compared to SEMS. In addition, LAMS had fewer overall adverse events (RR = 0.64, 95%CI [0.48, 0.87], P = 0.004). For specific adverse events, LAMS had fewer migration (RR = 0.37, 95%CI [0.19, 0.72], P = 0.003), occlusion (RR = 0.43, 95%CI [0.22, 0.82], P = 0.01) and infection (RR = 0.38, 95%CI [0.20, 0.70], P = 0.002). There was no significant difference in bleeding and perforation between the two stents. For hospital stay (days), LAMS group was similar to SEMS group (MD = - 3.34, 95%CI [- 7.71, - 1.03], P = 0.13). Regarding recurrence, LAMS group was fewer than SEMS group (RR = 0.41, 95%CI [0.21, 0.78], P = 0.007). CONCLUSION: Compared to traditional SEMS, LAMS has a higher clinical success rate, faster procedure time, fewer adverse events, similar hospital stay and lower recurrence rate in EUS-guided drainage of PFCs. LAMS is a good choice with a high technical success rate over 95%, and using a shorter length or "one-step" operation can further improve it. Richer placement experience is required for LAMS placement under EUS-guidance.

Major Indole Alkaloids in Evodia Rutaecarpa: The Latest Insights and Review of Their Impact on Gastrointestinal Diseases.

Evodia rutaecarpa, the near-ripe fruit of Euodia rutaecarpa (Juss.) Benth, Euodia rutaecarpa (Juss.) Benth. var. officinalis (Dode) Huang, or Euodia rutaecarpa (Juss.) Benth. var. bodinieri (Dode) Huang, is a famous herbal medicine with several biological activities and therapeutic values, which has been applied for abdominalgia, abdominal distension, vomiting, and diarrhea as a complementary and alternative therapy in clinic. Indole alkaloids, particularly evodiamine (EVO), rutaecarpine (RUT), and dedhydroevodiamine (DHE), are received rising attention as the major bioactivity compounds in Evodia rutaecarpa. Therefore, this review summarizes the physicochemical properties, pharmacological activities, pharmacokinetics, and therapeutic effects on gastrointestinal diseases of these three indole alkaloids with original literature collected by PubMed, Web of Science Core Collection, and CNKI up to June 2023. Despite sharing the same parent nucleus, EVO, RUT, and DHE have different structural and chemical properties, which result in different advantages of biological effects. In their wide range of pharmacological activities, the anti-migratory activity of RUT is less effective than that of EVO, and the neuroprotection of DHE is significant. Additionally, although DHE has a higher bioavailability, EVO and RUT display better permeabilities within blood-brain barrier. These three indole alkaloids can alleviate gastrointestinal inflammatory in particular, and EVO also has outstanding anti-cancer effect, although clinical trials are still required to further support their therapeutic potential.

Insights into the potential benefits of triphala polyphenols toward the promotion of resilience against stress-induced depression and cognitive impairment.

In response to environmental challenges, stress is a common reaction, but dysregulation of the stress response can lead to neuropsychiatric disorders, including depression and cognitive impairment. Particularly, there is ample evidence that overexposure to mental stress can have lasting detrimental consequences for psychological health, cognitive function, and ultimately well-being. In fact, some individuals are resilient to the same stressor. A major benefit of enhancing stress resilience in at-risk groups is that it may help prevent the onset of stress-induced mental health problems. A potential therapeutic strategy for maintaining a healthy life is to address stress-induced health problems with botanicals or dietary supplements such as polyphenols. Triphala, also known as Zhe Busong decoction in Tibetan, is a well-recognized Ayurvedic polyherbal medicine comprising dried fruits from three different plant species. As a promising food-sourced phytotherapy, triphala polyphenols have been used throughout history to treat a variety of medical conditions, including brain health maintenance. Nevertheless, a comprehensive review is still lacking. Here, the primary objective of this review article is to provide an overview of the classification, safety, and pharmacokinetics of triphala polyphenols, as well as recommendations for the development of triphala polyphenols as a novel therapeutic strategy for promoting resilience in susceptible individuals. Additionally, we summarize recent advances demonstrating that triphala polyphenols are beneficial to cognitive and psychological resilience by regulating 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) receptors, gut microbiota, and antioxidant-related signaling pathways. Overall, scientific exploration of triphala polyphenols is warranted to understand their therapeutic efficacy. In addition to providing novel insights into the mechanisms of triphala polyphenols for promoting stress resilience, blood brain barrier (BBB) permeability and systemic bioavailability of triphala polyphenols also need to be improved by the research community. Moreover, well-designed clinical trials are needed to increase the scientific validity of triphala polyphenols' beneficial effects for preventing and treating cognitive impairment and psychological dysfunction.

Probiotics improve symptoms of patients with COVID-19 through gut-lung axis: a systematic review and meta-analysis.

Background: Multi system symptoms such as gastrointestinal tract and respiratory tract exist in coronavirus disease 2019 (COVID-19) patients. There is a lack of reliable evidence to prove that probiotics are effective in improving these symptoms. In this study, we aimed to evaluate the efficacy of probiotics in meta-analysis. Methods: We systematically searched PubMed, Embase, Web of Science, and Cochrane Library up to February 15, 2023. Randomized controlled trials or high quality retrospective studies comparing the efficacy of probiotics as supplementation with non-probiotics in improving symptoms for patients with COVID-19 were included. This meta-analysis assessed endpoints using Review Manager 5.3. Result: Ten citations comprising 1198 patients with COVID-19 were included. The results showed that probiotics could increase the number of people with overall symptom improvement (RR = 1.62, 95% CI [1.10, 2.38], P = 0.01) and shorten the duration (days) of overall symptoms (MD = -1.26, 95% CI [-2.36, -0.16], P = 0.02). For the duration (days) of specific symptoms, probiotics could improve diarrhea (MD = -2.12, 95% CI [-2.41, -1.83], P < 0.00001), cough (MD = -2.21, 95% CI [-4.56, 0.13], P = 0.06) and shortness of breath (MD = -1.37, 95% CI [-2.22, -0.53], P = 0.001). Probiotics had no obvious effect on fever, headache and weakness. For inflammation, probiotics could effectively reduce C-reactive Protein (CRP) serum level (mg/L) (MD = -4.03, 95% CI [-5.12, -2.93], P < 0.00001). Regarding hospital stay (days), probiotics group was shorter than non-probiotics group (MD = -0.98, 95% CI [-1.95, -0.01], P = 0.05). Conclusion: To some extent probiotics could improve the overall symptoms, inflammatory reaction and shorten hospital stay of patients with COVID-19. Probiotics may improve gastrointestinal symptoms (such as improving intestinal flora and reducing the duration of diarrhea) and further improve respiratory symptoms through the gut-lung axis. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=398309, identifier: CRD42023398309.

Identification of hub genes and potential ceRNA networks of diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM), a common complication of diabetes, is defined as ventricular dysfunction in the absence of underlying heart disease. Noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), play a crucial role in the development of DCM. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify key modules in DCM-related pathways. DCM-related miRNA-mRNA network and DCM-related ceRNA network were constructed by miRNA-seq to identify hub genes in these modules. We identified five hub genes that are associated with the onset of DCM, including Troponin C1 (Tnnc1), Phospholamban (Pln), Fatty acid binding proteins 3 (Fabp3), Popeye domain containing 2 (Popdc2), and Tripartite Motif-containing Protein 63 (Trim63). miRNAs that target the hub genes were mainly involved in TGF-ß and Wnt signaling pathways. GO BP enrichment analysis found these miRNAs were involved in the signaling of TGF-ß and glucose homeostasis. Q-PCR results found the gene expressions of Pln, Fabp3, Trim63, Tnnc1, and Popdc2 were significantly increased in DCM. Our study identified five hub genes (Tnnc1, Pln, Fabp3, Popdc2, Trim63) whose associated ceRNA networks are responsible for the onset of DCM.

Efficacy and Safety of Direct Oral Anticoagulants Compared With Heparin for Preventing Thromboembolism in Hospitalized Patients With COVID-19: A Systematic Review and Meta-Analysis.

A high rate of thromboembolism and a high risk of death have been reported regarding hospitalized patients with coronavirus disease 2019 (COVID-19). Recently, we noticed that clinicians in some comparative studies used direct oral anticoagulants (DOACs) to prevent thromboembolism in patients with COVID-19. However, it is uncertain whether DOACs are better than recommended heparin for hospitalized patients with COVID-19. Therefore, a direct comparison of the prophylactic effects and safety between DOACs and heparin is needed. We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from 2019 to December 1, 2022. Randomized controlled trials or retrospective studies comparing the efficacy or safety of DOACs with that of heparin in preventing thromboembolism for hospitalized patients with COVID-19 were included. We assessed endpoints and publication bias using Stata 14.0. Five studies comprising 1360 hospitalized COVID-19 patients with mild to moderate cases were identified in the databases. Comparing the embolism incidence, we found that DOACs had a better effect than heparin, mainly low-molecular-weight heparin (LMWH), in preventing thromboembolism (risk ratio [RR] = 0.63, 95% confidence interval [CI] [0.43-0.91], P = 0.014). Considering safety, DOACs resulted in less bleeding than heparin during hospitalization (RR = 0.52, 95% CI [0.11-2.44], P = 0.411). Similar mortality was discovered in the 2 groups (RR = 0.94, 95% CI [0.59-1.51], P = 0.797). In noncritically hospitalized patients with COVID-19, DOACs are superior to heparin, even LMWH, in preventing thromboembolism. Compared with heparin, DOACs have a lower trend of bleeding and yield a similar mortality rate. Therefore, DOACs may be a better alternative for patients with mild to moderate COVID-19.

Exosomes incorporated with black phosphorus quantum dots attenuate retinal angiogenesis via disrupting glucose metabolism.

Black phosphorus quantum dots (BPQDs) have shown potential in tumor therapy, however, their anti-angiogenic functions have not been studied. Although BPQDs are easily degraded to non-toxic phosphrous, the reported toxicity, poor stability, and non-selectivity largely limit their further application in medicine. In this study, a vascular targeting, biocompatible, and cell metabolism-disrupting nanoplatform is engineered by incorporating BPQDs into exosomes modified with the Arg-Gly-Asp (RGD) peptide (BPQDs@RGD-EXO nanospheres, BREs). BREs inhibit endothelial cells (ECs) proliferation, migration, tube formation, and sprouting in vitro. The anti-angiogenic role of BREs in vivo is evaluated using mouse retinal vascular development model and oxygen-induced retinopathy model. Combined RNA-seq and metabolomic analysis reveal that BREs disrupt glucose metabolism, which is further confirmed by evaluating metabolites, ATP production and the c-MYC/Hexokinase 2 pathway. These BREs are promising anti-angiogenic platforms for the treatment of pathological retinal angiogenesis with minimal side effects.

A macrophage membrane-coated mesoporous silica nanoplatform inhibiting adenosine A2AR via in situ oxygen supply for immunotherapy.

Immunotherapy has achieved remarkable research outcomes and shows the potential to cure cancer. However, its therapeutic response is limited in terms of the immunosuppressive tumor microenvironment induced by hypoxia, in which the adenosinergic A2A receptor (A2AR) pathway is mainly participated. Here, we developed a novel core/shell structured nanoplatform composed of macrophage membrane-coated mesoporous silica nanoparticles which loaded catalase, doxorubicin (Dox), and resiquimod (R848), to promote the efficacy of immunotherapy. The nanoplatform is able to actively target the tumor site via ligand binding, and the A2AR of T regulatory (Treg) cells can further be blocked due to in situ oxygen production by hydrogen peroxide catalysis. Meanwhile, Dox and R848 released from the nanoplatform can induce immunogenic cell death and enhance the activation of dendritic cells (DCs), respectively. Thus, the improved microenvironment by A2AR blockade and the stimulation of the DCs to enhance the CD8+ T cells mediated immune response were achieved. Consequently, the expression of Treg cells decreased to 9.79% in tumor tissue and the inhibition rate of tumor growth reached 73.58%. Therefore, this nanoplatform provides a potential strategy for clinical application in cancer immunotherapy.

Angelica sinensis Polysaccharide and Astragalus membranaceus Polysaccharide Accelerate Liver Regeneration by Enhanced Glycolysis via Activation of JAK2/STAT3/HK2 Pathway.

The promotion of liver regeneration is crucial to avoid liver failure after hepatectomy. Angelica sinensis polysaccharide (ASP) and Astragalus membranaceus polysaccharide (AMP) have been identified as being associated with hepatoprotective effects. However, their roles and specific mechanisms in liver regeneration remain to be elucidated. In the present study, it suggested that the respective use of ASP or AMP strikingly promoted hepatocyte proliferation in vitro with a wide range of concentrations (from 12.5 µg/mL to 3200 µg/mL), and a stronger promoting effect was observed in combined interventions. A significantly enhanced liver/body weight ratio (4.20%) on day 7 and reduced serum transaminase (ALT 243.53 IU/L and AST 423.74 IU/L) and total bilirubin (52.61 IU/L) levels on day 3 were achieved by means of ASP-AMP administration after partial hepatectomy in mice. Metabonomics showed that differential metabolites were enriched in glycolysis with high expression of beta-d-fructose 6-phosphate and lactate, followed by significantly strengthened lactate secretion in the supernatant (0.54) and serum (0.43) normalized to control. Upon ASP-AMP treatment, the knockdown of hexokinase 2 (HK2) or inhibited glycolysis caused by 2-deoxy-d-glucose decreased hepatocyte proliferation in vitro and in vivo. Furthermore, pathway analysis predicted the role of JAK2/STAT3 pathway in ASP-AMP-regulated liver regeneration, and phosphorylation of JAK2 and STAT3 was proven to be elevated in this promoting process. Finally, downregulated expression of HK2, an attenuated level of lactate secretion, and reduced hepatocyte proliferation were displayed when STAT3 was knocked out in vitro. Therefore, it can be concluded that ASP-AMP accelerated liver regeneration and exerted a hepatoprotective effect after hepatectomy, in which the JAK2/STAT3/HK2 pathway was actively involved in activating glycolysis.

Multifunctional biomaterial platforms for blocking the fibrosis process and promoting cellular restoring effects in myocardial fibrosis therapy.

Myocardial fibrosis is the result of abnormal healing after acute and chronic myocardial damage and is a direct cause of heart failure and cardiac insufficiency. The clinical approach is to preserve cardiac function and inhibit fibrosis through surgery aimed at dredging blood vessels. However, this strategy does not adequately address the deterioration of fibrosis and cardiac function recovery. Therefore, numerous biomaterial platforms have been developed to address the above issues. In this review, we summarize the existing biomaterial delivery and restoring platforms, In addition, we also clarify the therapeutic strategies based on biomaterial platforms, including general strategies to block the fibrosis process and new strategies to promote cellular restoring effects. The development of structures with the ability to block further fibrosis progression as well as to promote cardiomyocytes viability should be the main research interests in myocardial fibrosis, and the reestablishment of structures necessary for normal cardiac function is central to the treatment of myocardial fibrosis. Finally, the future application of biomaterials for myocardial fibrosis is also highlighted.

The role of post-translational modifications in driving abnormal cardiovascular complications at high altitude.

The high-altitude environment is characterized by hypobaric hypoxia, low temperatures, low humidity, and high radiation, which is a natural challenge for lowland residents entering. Previous studies have confirmed the acute and chronic effects of high altitude on the cardiovascular systems of lowlanders. Abnormal cardiovascular complications, including pulmonary edema, cardiac hypertrophy and pulmonary arterial hypertension were commonly explored. Effective evaluation of cardiovascular adaptive response in high altitude can provide a basis for early warning, prevention, diagnosis, and treatment of altitude diseases. At present, post-translational modifications (PTMs) of proteins are a key step to regulate their biological functions and dynamic interactions with other molecules. This process is regulated by countless enzymes called "writer, reader, and eraser," and the performance is precisely controlled. Mutations and abnormal expression of these enzymes or their substrates have been implicated in the pathogenesis of cardiovascular diseases associated with high altitude. Although PTMs play an important regulatory role in key processes such as oxidative stress, apoptosis, proliferation, and hypoxia response, little attention has been paid to abnormal cardiovascular response at high altitude. Here, we reviewed the roles of PTMs in driving abnormal cardiovascular complications at high altitude.

ACSL4 as a Potential Target and Biomarker for Anticancer: From Molecular Mechanisms to Clinical Therapeutics.

Cancer is a major public health problem around the world and the key leading cause of death in the world. It is well-known that glucolipid metabolism, immunoreaction, and growth/death pattern of cancer cells are markedly different from normal cells. Recently, acyl-CoA synthetase long-chain family 4 (ACSL4) is found be participated in the activation of long chain fatty acids metabolism, immune signaling transduction, and ferroptosis, which can be a promising potential target and biomarker for anticancer. Specifically, ACSL4 inhibits the progress of lung cancer, estrogen receptor (ER) positive breast cancer, cervical cancer and the up-regulation of ACSL4 can improve the sensitivity of cancer cells to ferroptosis by enhancing the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS). However, it is undeniable that the high expression of ACSL4 in ER negative breast cancer, hepatocellular carcinoma, colorectal cancer, and prostate cancer can also be related with tumor cell proliferation, migration, and invasion. In the present review, we provide an update on understanding the controversial roles of ACSL4 in different cancer cells.

Proteomic and Morphological Profiling of Mice Ocular Tissue During High-altitude Acclimatization Process: An Animal Study at Lhasa.

Purpose: High-altitude environment mainly with hypobaric hypoxia could induce pathological alterations in ocular tissue. Previous studies have mostly focused on sporadic case reports and simulated high-altitude hypoxia experiments. This aim of this study was to explore the proteomic and morphological changes of ocular tissue in mice at real altitude environment. Methods: In this study, mice were flown from Chengdu (elevation: 500 m) to Lhasa (elevation: 3600 m). After exposure for 1day, 3, 6, 10, 20, 30, and 40days, the mice were euthanatized to obtain blood and ocular tissue. Serological tests, ocular pathological examinations, integral ocular proteomics analysis, and Western blot were conducted. Results: We focused on acute phase (1-3 days) and chronic phase (>30 days) during high-altitude acclimatization. Serum interleukin-1 was increased at 3 days, while superoxide dismutase, interleukin-6, and tumor necrosis factor-α showed no statistical changes. H&E staining demonstrated that the cornea was edematous at 3 days and exhibited slower proliferation at 30 days. The choroid showed a consistently significant thickening, while there existed no noticeable changes in retinal thickness. Overall, 4073 proteins were identified, among which 71 and 119 proteins were detected to have significant difference at 3 days and 40 days when compared with the control group. Functional enrichment analysis found the differentiated proteins at 3 days exposure functionally related with response to radiation, dephosphorylation, negative regulation of cell adhesion, and erythrocyte homeostasis. Moreover, the differential profiles of the proteins at 40 days exposure exhibited changes of regulation of complement activation, regulation of protein activation cascade, regulation of humoral immune response, second-messenger-mediated signaling, regulation of leukocyte activation, and cellular iron homeostasis. Interestingly, we found the ocular proteins with lactylation modification were increased along high-altitude adaptation. Conclusion: This is the first work reporting the ocular proteomic and morphological changes at real high-altitude environment. We expect it would deep the understanding of ocular response during altitude acclimatization.

Advances in research on the protective mechanisms of traditional Chinese medicine (TCM) in myocardial ischaemia-reperfusion injury.

CONTEXT: Developing effective drugs to treat myocardial ischaemia-reperfusion (MI/R) injury is imperative. Traditional Chinese medicines (TCMs) have had considerable success in the treatment of cardiovascular diseases. Elucidating the mechanisms by which TCMs improve MI/R injury can supplement the literature on MI/R prevention and treatment. OBJECTIVE: To summarise TCMs and their main protective mechanisms against MI/R injury reported over the past 40 years. METHODS: Relevant literature published between 1980 and 2020 in Chinese and English was retrieved from the Web of Science, PubMed, SpringerLink, PubMed Central, Scopus, and Chinese National Knowledge Infrastructure (CNKI) databases. Search terms included 'medicinal plants', 'myocardial ischaemia reperfusion injury', 'Chinese medicine prescriptions', 'mechanisms', 'prevention', 'treatment' and 'protection'. For inclusion in the analysis, medicinal plants had to be searchable in the China Medical Information Platform and Plant Database. RESULTS: We found 71 medicinal species (from 40 families) that have been used to prevent MI/R injury, of which Compositae species (8 species) and Leguminosae species (7 species) made up the majority. Most of the effects associated with these plants are described as antioxidant and anti-inflammatory. Furthermore, we summarised 18 kinds of Chinese compound prescriptions, including the compound Danshen tablet and Baoxin pill, which mainly reduce oxidative stress and regulate mitochondrial energy metabolism. DISCUSSION AND CONCLUSIONS: We summarised TCMs that protect against MI/R injury and their pharmacological mechanisms. This in-depth explanation of the roles of TCMs in MI/R injury protection provides a theoretical basis for the research and development of TCM-based treatment drugs.

Long non-coding RNA MIAT is involved in the regulation of pyroptosis in diabetic cardiomyopathy via targeting miR-214-3p.

Diabetic cardiomyopathy (DCM) is one of the most common complications of diabetes without effective treatment options. Its pathogenesis is complex and remains unclear. Long non-coding RNA (lncRNA) MIAT allele has been reported to be enriched in DCM patients and activate a pyroptosis program in hypoxia-induced H9c2 cells. Thus, whether MIAT played a role in DCM pyroptosis remains to be clarified. In the study, the expression of MIAT was found elevated in the serum of diabetic patients, as well as in high-glucose induced cardiomyocytes and diabetic mice. Further, the expression levels of CASP1 and pyroptosis correlation factors (IL-1 and IL-18) were downregulated after silencing MIAT. Through modeling and validation experiments, we then confirmed that the MIAT-miR-214-3p-CASP1 axis serves as an essential point in pyroptosis of DCM mice. These results suggested that silencing MIAT would be a potential treatment strategy for DCM.