Proteomics and ß-hydroxybutyrylation Modification Characterization in the Hearts of Naturally Senescent Mice.

Aging is widely accepted as an independent risk factor for cardiovascular disease (CVD), which contributes to increasing morbidity and mortality in the elderly population. Lysine ß-hydroxybutyrylation (Kbhb) is a novel post-translational modification (PTM), wherein ß-hydroxybutyrate is covalently attached to lysine ε-amino groups. Recent studies have revealed that histone Kbhb contributes to tumor progression, diabetic cardiomyopathy progression, and postnatal heart development. However, no studies have yet reported a global analysis of Kbhb proteins in aging hearts or elucidated the mechanisms underlying this modification in the process. Herein, we conducted quantitative proteomics and Kbhb PTM omics to comprehensively elucidate the alterations of global proteome and Kbhb modification in the hearts of aged mice. The results revealed a decline in grip strength and cardiac diastolic function in 22-month-old aged mice compared to 3-month-old young mice. High-throughput liquid chromatogram-mass spectrometry analysis identified 1710 ß-hydroxybutyrylated lysine sites in 641 proteins in the cardiac tissue of young and aged mice. Additionally, 183 Kbhb sites identified in 134 proteins exhibited significant differential modification in aged hearts (fold change (FC) > 1.5 or <1/1.5, p < 0.05). Notably, the Kbhb-modified proteins were primarily detected in energy metabolism pathways, such as fatty acid elongation, glyoxylate and dicarboxylate metabolism, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, these Kbhb-modified proteins were predominantly localized in the mitochondria. The present study, for the first time, provides a global proteomic profile and Kbhb modification landscape of cardiomyocytes in aged hearts. These findings put forth novel possibilities for treating cardiac aging and aging-related CVDs by reversing abnormal Kbhb modifications.

Quantification and Proteomic Characterization of ß-Hydroxybutyrylation Modification in the Hearts of AMPKα2 Knockout Mice.

AMP-activated protein kinase alpha 2 (AMPKα2) regulates energy metabolism, protein synthesis, and glucolipid metabolism myocardial cells. Ketone bodies produced by fatty acid ß-oxidation, especially ß-hydroxybutyrate, are fatty energy-supplying substances for the heart, brain, and other organs during fasting and long-term exercise. They also regulate metabolic signaling for multiple cellular functions. Lysine ß-hydroxybutyrylation (Kbhb) is a ß-hydroxybutyrate-mediated protein posttranslational modification. Histone Kbhb has been identified in yeast, mouse, and human cells. However, whether AMPK regulates protein Kbhb is yet unclear. Hence, the present study explored the changes in proteomics and Kbhb modification omics in the hearts of AMPKα2 knockout mice using a comprehensive quantitative proteomic analysis. Based on mass spectrometry (LC-MS/MS) analysis, the number of 1181 Kbhb modified sites in 455 proteins were quantified between AMPKα2 knockout mice and wildtype mice; 244 Kbhb sites in 142 proteins decreased or increased after AMPKα2 knockout (fold change >1.5 or <1/1.5, p < 0.05). The regulation of Kbhb sites in 26 key enzymes of fatty acid degradation and tricarboxylic acid cycle was noted in AMPKα2 knockout mouse cardiomyocytes. These findings, for the first time, identified proteomic features and Kbhb modification of cardiomyocytes after AMPKα2 knockout, suggesting that AMPKα2 regulates energy metabolism by modifying protein Kbhb.

Pulmonary interstitial lesions in pemphigus mouse model: Verifying pemphigus may not be only limited to skin and mucosa.

Interstitial lung disease (ILD) has been identified as a prevalent complication and significant contributor to mortality in individuals with pemphigus. In this study, a murine model of pemphigus was developed through the subcutaneous administration of serum IgG obtained from pemphigus patients, allowing for an investigation into the association between pemphigus and ILD. Pulmonary interstitial lesions were identified in the lungs of a pemphigus mouse model through histopathology, RT-qPCR and Sircol assay analyses. The severity of these lesions was found to be positively associated with the concentration of IgG in the injected serum. Additionally, DIF staining revealed the deposition of serum IgG in the lung tissue of pemphigus mice, indicating that the subcutaneous administration of human IgG directly impacted the lung tissue of the mice, resulting in damage. This study confirms the presence of pulmonary interstitial lesions in the pemphigus mouse model and establishes a link between pemphigus and ILD.

Amino acid starvation-induced LDLR trafficking accelerates lipoprotein endocytosis and LDL clearance.

Mammalian cells utilize Akt-dependent signaling to deploy intracellular Glut4 toward cell surface to facilitate glucose uptake. Low-density lipoprotein receptor (LDLR) is the cargo receptor mediating endocytosis of apolipoprotein B-containing lipoproteins. However, signaling-controlled regulation of intracellular LDLR trafficking remains elusive. Here, we describe a unique amino acid stress response, which directs the deployment of intracellular LDLRs, causing enhanced LDL endocytosis, likely via Ca2+ and calcium/calmodulin-dependent protein kinase II-mediated signalings. This response is independent of induction of autophagy. Amino acid stress-induced increase in LDL uptake in vitro is comparable to that by pravastatin. In vivo, acute AAS challenge for up to 72 h enhanced the rate of hepatic LDL uptake without changing the total expression level of LDLR. Reducing dietary amino acids by 50% for 2 to 4 weeks ameliorated high fat diet-induced hypercholesterolemia in heterozygous LDLR-deficient mice, with reductions in both LDL and VLDL fractions. We suggest that identification of signaling-controlled regulation of intracellular LDLR trafficking has advanced our understanding of the LDLR biology, and may benefit future development of additional therapeutic strategies for treating hypercholesterolemia.

Integrated metabolomics and phosphoproteomics reveal the protective role of exosomes from human umbilical cord mesenchymal stem cells in naturally aging mouse livers.

BACKGROUND: Aging is characterized by a general decline in cellular function, which ultimately affects whole body homeostasis. This study aimed to investigate the effects and underlying mechanisms of exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSC-exos) on the livers of naturally aging mice. METHOD: Twenty-two-month-old C57BL6 mice were used as a natural aging animal model, divided into a saline-treated wild-type aged control group (WT-AC) and a hUCMSC-exo-treated group (WT-AEX), and then detected by morphology, metabolomics and phosphoproteomics. RESULTS: Morphological analysis showed that hUCMSC-exos ameliorated structural disorder and decreased markers of senescence and genome instability in aging livers. Metabolomics showed that hUCMSC-exos decreased the contents of saturated glycerophospholipids, palmitoyl-glycerols and eicosanoid derivatives associated with lipotoxicity and inflammation, consistent with the decreased phosphorylation of metabolic enzymes, such as propionate-CoA ligase (Acss2), at S267 detected by phosphoproteomics. Moreover, phosphoproteomics indicated that hUCMSC-exos reduced the phosphorylation of proteins participating in nuclear transport and cancer signaling, such as heat shock protein HSP90-beta (Hsp90ab1) at S226 and nucleoprotein TPR (Tpr) at S453 and S379, while increasing those involved in intracellular communication, such as calnexin (Canx) at S563 and PDZ domain-containing protein 8 (Pdzd8). Finally, phosphorylated HSP90ß and Tpr were verified predominantly in hepatocytes. CONCLUSION: HUCMSC-exos improved metabolic reprogramming and genome stability mainly associated with phosphorylated HSP90ß in hepatocytes in natural aging livers. This work provides a comprehensive resource of biological data by omics to support future investigations of hUCMSC-exos in aging.

D-pinitol alleviates diabetic cardiomyopathy by inhibiting the optineurin-mediated endoplasmic reticulum stress and glycophagy signaling pathway.

Diabetic cardiomyopathy (DCM) is an important complication resulting in heart failure and death of diabetic patients. However, there is no effective drug for treatments. This study investigated the effect of D-pinitol (DP) on cardiac injury using diabetic mice and glycosylation injury of cardiomyocytes and its molecular mechanisms. We established the streptozotocin-induced SAMR1 and SAMP8 mice and DP (150 mg/kg/day) intragastrically and advanced glycation end-products (AGEs)-induced H9C2 cells. H9C2 cells were transfected with optineurin (OPTN) siRNA and overexpression plasmids. The metabolic disorder indices, cardiac dysfunction, histopathology, immunofluorescence, western blot, and immunoprecipitation were investigated. Our results showed that DP reduced the blood glucose and AGEs, and increased the expression of heart OPTN in diabetic mice and H9C2 cells, thereby inhibiting the endoplasmic reticulum stress (GRP78, CHOP) and glycophagy (STBD1, GABARAPL1), and alleviating the myocardial apoptosis and fibrosis of DCM. The expression of filamin A as an interaction protein of OPTN downregulated by AGEs decreased OPTN abundance. Moreover, OPTN siRNA increased the expression of GRP78, CHOP, STBD1, and GABARAPL1 and inhibited the expression of GAA via GSK3ß phosphorylation and FoxO1. DP may be helpful to treat the onset of DCM. Targeting OPTN with DP could be translated into clinical application in the fighting against DCM.

Small DNAs That Specifically and Tightly Bind Transition Metal Ions.

Specific DNA-binding to metal ions is a long-standing fundamental research topic with great potential to transform into nano/biotechnology and therapeutics applications. Herein, based on the mobility change of DNA in denaturing gels, we develop a selection strategy to discover a series of 40-45 nt small DNAs that can bind Zn2+ and Cd2+ specifically and tightly. The Zn2+- and Cd2+-bound DNA complexes can even tolerate harsh denaturing conditions of 8 M urea and 50 mM EDTA. The discovery not only exposes a new class of transition metal ion-binding DNAs but also provides potentially a new tool for targeting drug therapies based on metal ions.

Photosensitivity is an important cause of refractory facial erythema in atopic dermatitis: A retrospective study of 82 Chinese patients.

BACKGROUND: Ultraviolet radiation can aggravate facial erythema in atopic dermatitis (AD) patients. OBJECTIVE: To investigate the photobiological testing results of Chinese AD patients with refractory facial erythema. METHODS: We conducted a retrospective analysis of 82 AD patients with refractory facial erythema who visited our department during 2004-2021. All of them completed phototesting and photopatch testing. RESULTS: 82 patients were enrolled in the study, and 53 (64.6%) were between 18 and 30 years old. 51.2% (42/82) had positive phototesting results and were considered photosensitive AD (PhAD) patients. One-third of them were both allergic to ultraviolet A and ultraviolet B. 65.9% (54/82) suffered from photoallergic contact dermatitis. Chlorpromazine (50.7%), potassium dichromate (13.2%), and thimerosal (11.8%) were the top three common photoallergens. Overall, 86.3% of AD patients with refractory facial erythema had direct photoallergy or photocontact allergy. PhAD patients had fewer allergic comorbidities than the other group (p = .007). More non-PhAD patients (55.0%) suffered from AD at 2-14 years old (p = .015). CONCLUSIONS: Photosensitivity contributes a lot to the facial lesions of AD patients, especially in their 20s. 86.3% of these patients had direct photoallergy or photocontact allergy. Therefore, AD patients with facial erythema should undergo phototesting and photopatch testing routinely.

Chronic actinic dermatitis: A 5-year clinical analysis of 488 patients in China.

BACKGROUND/PURPOSE: Chronic actinic dermatitis (CAD) is a spectrum of diseases with chronic photosensitivity occurring mostly among middle-aged and older men. We seek to explore the characteristics and pathogenesis of CAD among the Chinese population. METHODS: The medical records of 488 CAD cases diagnosed by phototesting at Huashan Hospital, Fudan University from January 2014 to December 2018 were analyzed retrospectively. RESULTS: Among the 488 patients, 344 were male and 144 were female. 84.8% of the cases were over 40 years old at the age of onset, while the remaining with an early age of onset had a prevalence of atopic history of 21.6%. Up to 45.0% of the patients reported excessive sun exposure and outdoor activities before the initiation of symptoms. The typical skin lesions were erythema, papules and plaques laid predominantly in sun-exposed areas. 42.8% of the cases showed sensitivity to UVB only, 20.7% were both sensitive to UVA and UVB, and 18.2% had UVA sensitivity only. The most predominant photoallergens were chlorpromazine (80.1%), thimerosal (17.2%), potassium dichromate (12.7%), etc. The most prevalent patch test allergens were potassium dichromate (24.4%), thimerosal (20.5%), formaldehyde (16.8%), etc. CONCLUSIONS: CAD was more commonly seen in males over 40 years old. The action spectrum of Chinese patients is primarily in the UVB range. Exposure to excessive sunlight or contact allergens and photoallergens are important risk factors. Photobiology tests are essential in detecting photosensitivity and recognizing potential photosensitizers. Early avoidance of confirmed photoallergens and sun exposure may prevent photosensitive reactions from progressing into persistent photosensitivity.

S100A9 promotes inflammatory response in diabetic nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) has been previously shown to be associated with diabetes mellitus (DM) which is one of the most decisive risk factors for the faster progression of NAFLD to nonalcoholic steatohepatitis (NASH), fibrosis or advanced cirrhosis. However, the critical molecular pathway involved in the development of diabetic-induced liver injury is unclear. By the proteomic study of liver from high-fat diet (HFD)/streptozotocin(STZ)-induced diabetic mice, we revealed that the upregulation of S100A9 was involved in the development of NAFLD with DM. Moreover, we found that S100A9 silencing decreased proinflammatory response and inhibited the TLR4-NF-κB signaling in in-vitro study. Our findings provide new perspectives into the pivotal role of S100A9 for development of diabetic NAFLD and revealed that S100A9 is a critical molecule that links liver injury to inflammation of NAFLD with DM.

Exosomes from human umbilical cord mesenchymal stem cells protect aortas in Db/db mice characterized by combination of metabolomics and proteomics.

Diabetic cardiovascular complication is a common systemic disease with high morbidity and mortality worldwide. We hypothesise that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs-exos) can rescue these disorders and alleviate vascular remodeling in diabetes. Morphological, non-targeted metabolomics and 4D label-free proteomics techniques were used to analyze the aortas of db/m mice as normal control group (NCA), saline treated db/db mice (DMA), and hUCMSCs-exos treated db/db mice (DMTA), and to clarify the molecular mechanism of the protection of hUCMSCs-exos in vascular remodeling from a new point of view. The results showed that 74 metabolites were changed significantly in diabetic aortas, of which 15 were almost restored by hUCMSCs-exos. In proteomics, 30 potential targets such as Stromal cell-derived factor 2-like protein 1, Leukemia inhibitory factor receptor, Peroxisomal membrane protein and E3 ubiquitin-protein ligase MYCBP2 were detected. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based analysis showed that Central carbon metabolism in cancer and Galactose metabolism pathway were up-regulated to near normal by hUCMSCs-exos in metabolomics, with janus associated kinase-signal transducer and activator of transcription (JAK-STAT) pathway displayed in proteomics. According to bioinformatics and integrated analysis, these targeted molecules of hUCMSCs-exos to attenuate the vascular remodeling were mainly associated with regulation of energy metabolism, oxidative stress, inflammation, and cellular communications. This study provided a reference for the therapy of diabetes-induced cardiovascular complications.

CX-5461 is a potent immunosuppressant which inhibits T cell-mediated alloimmunity via p53-DUSP5.

CX-5461 is a first-in-class selective RNA polymerase I inhibitor. Previously we found that CX-5461 had anti-inflammatory activities. In this study we characterized potential immunosuppressive effects of CX-5461 and explored the underlying mechanisms. Allogeneic skin transplantation model (BALB/c to C57BL/6 mice) and heterotopic heart transplantation model (F344 to Lewis rats) were used. We showed that CX-5461 was a potent inhibitor of alloimmunity which prevented acute allograft rejections. CX-5461 treatment was invariably associated with expansion of the regulatory T cell population. In vitro, CX-5461 inhibited agonists-induced T cell activation. CX-5461 consistently inhibited the expression of interferon-γ and interleukin - 2, key mediators of T cell-mediated alloimmunity. Mechanistically, CX-5461-induced immunosuppression was, at least partly, dependent on the p53-DUSP5 (dual-specificity phosphatase 5) axis and subsequent antagonism of the Erk1/2 mitogen-activated protein kinase pathway. In conclusion, our results suggest that CX-5461 is a promising candidate of a novel class of immunosuppressant which may be used as an alternative to the currently approved anti-rejection therapies.

Dupilumab combined with low-dose systemic steroid therapy improves efficacy and safety for bullous pemphigoid.

Routine systemic therapy for bullous pemphigoid (BP) has been challenged due to the inevitably adverse effects. According to the successful applications of dupilumab in BP cases reported, therefore, we investigate the real-life efficacy and safety of dupilumab combined with low-dose oral steroid for BP. A cohort of BP patients who received either dupilumab plus low-dose methylprednisolone (dupilumab group) or merely methylprednisolone (control group) was retrospectively reviewed. The time to disease control was investigated. Additionally, the control dose and cumulative dosage of steroids, Bullous Pemphigoid Disease Area Index (BPDAI) scores, pruritus scores, and adverse events were assessed. A total of 40 patients, with 20 in each group, were retrospectively studied. The time to disease control was shorter in the dupilumab group than the control group (14 days vs. 19 days, p = 0.043). When the disease was controlled, the control dose and cumulative dosage of methylprednisolone in the dupilumab group were substantially lower than those of the control (24.6 mg vs. 48.8 mg, 376.8 mg vs. 985.6 mg, both p < 0.01). Compared with the control, the percentage change from baseline in BPDAI scores and pruritus scores were both significantly reduced, and the adverse events were also less frequent in the dupilumab group. The combination therapy of dupilumab plus low-dose methylprednisolone exhibits superior efficacy and safety in comparison with the current first-line systemic therapy for BP.

Examining Chinese Users' Feedback Comments on HIV Self-testing Kits From e-Commerce Platforms: Thematic and Content Analysis.

BACKGROUND: HIV self-testing is preferred by many Chinese people for its convenience and confidentiality. However, most studies on HIV self-testing (HIVST) uptake in China overfocused on men who have sex with men and overrelied on obtrusive methods such as surveys and interviews to collect data. OBJECTIVE: We aimed to explore Chinese HIVST kit users' authentic experience via their feedback comments posted on e-commerce platforms using an unobtrusive approach. METHODS: In total, 21,018 feedback comments about buying and using HIVST kits posted on Chinese e-commerce platforms (Tmall and Pinduoduo) were collected. An inductive thematic analysis based on a random sample of 367 comments yielded several thematic features. These thematic features were developed into coding categories for a quantitative content analysis of another random sample of 1857 comments. RESULTS: Four themes were identified in the first study, including the expression of positive and negative emotions after and before getting the test, respectively, calling for living a clean and moral life in the future, comments on the sellers and HIVST kits, and the reasons for buying HIVST kits. The results from the second study suggested that there were significant associations between different platforms and several thematic features. Nearly 50% of the comments were related to the product itself and the disclosures of HIV-negative test results. More than 25% of the comments showed users' feelings of gratefulness after receiving negative test results such as "thank heavens for sparing my life." CONCLUSIONS: The results suggested that Chinese users relied on HIVST kits to reduce and prevent HIV infection, while they also considered HIV infection a punishment related to moral violation such as being sexually promiscuous. The traditional Chinese health belief that health is influenced by one's morality still persists among some Chinese users. Many users also lacked appropriate knowledge about HIV transmission and self-testing kits.

Benzo(α)pyrene induces oxidative stress and inflammation in human vascular endothelial cells through AhR and NF-κB pathways.

Exposure to polycyclic aromatic hydrocarbons (PAHs) contributes to development and exacerbation of atherosclerosis and cardiovascular disease. However, the underlying molecular mechanisms remain elusive. In the current study, the effect of benzo(α)pyrene (BaP) in human umbilical vein endothelial cells (HUVECs) was investigated, including its impact on apoptosis, cell viability, oxidative stress and inflammatory cytokine release. The role of aryl hydrocarbon receptor (AhR) and NF-κB signaling pathways involved in BaP-induced oxidative stress and inflammation was further investigated. Exposure to BaP induced cell apoptosis and terminal oxidative stress and inflammation responses in HUVECs. BaP also increased the expression of ICAM-1 and VCAM-1. Furthermore, BaP treatment of HUVECs activated AhR and NF-κB signaling pathways, and promoted reactive oxygen species generation and inflammatory cytokine release. The current findings suggest that BaP induced inflammatory cytokine release from HUVECs through oxidative stress accompanied with AhR and NF-κB pathway activation.

The p53 pathway in vasculature revisited: A therapeutic target for pathological vascular remodeling?

Pathological vascular remodeling contributes to the development of restenosis following intraluminal interventions, transplant vasculopathy, and pulmonary arterial hypertension. Activation of the tumor suppressor p53 may counteract vascular remodeling by inhibiting aberrant proliferation of vascular smooth muscle cells and repressing vascular inflammation. In particular, the development of different lines of small-molecule p53 activators ignites the hope of treating remodeling-associated vascular diseases by targeting p53 pharmacologically. In this review, we discuss the relationships between p53 and pathological vascular remodeling, and summarize current experimental data suggesting that drugging the p53 pathway may represent a novel strategy to prevent the development of vascular remodeling.

The protective effects of grape seed procyanidin B2 against asporin mediates glycated low-density lipoprotein induced-cardiomyocyte apoptosis and fibrosis.

The progression of diabetic cardiomyopathy is related to cardiomyocyte dysfunction and apoptosis. Our previous studies showed that asporin (ASPN) was significantly increased in the myocardium of db/db mice through proteomics, and grape seed procyanidin B2 (GSPB2) significantly inhibited the expression of ASPN in the heart of db/db mice. We report here that ASPN played a critical role in glycated low-density lipoproteins (gly-LDL) induced-cardiomyocyte apoptosis. We found that gly-LDL upregulated ASPN expression. ASPN increased H9C2 cardiomyocyte apoptosis with down-regulation of Bcl-2, upregulation of transforming growth factor-ß1, Bax, collagen III, fibronectin, and phosphorylation of smad2 and smad3. However, GSPB2 treatment reversed ASPN-induced impairments in H9C2 cardiomyocytes. These results provide evidence for the cardioprotective action of GSPB2 against ASPN injury, and thus suggest a new target for fighting against diabetic cardiomyopathy.

Synthesis of 'dual-key-and-lock' drug carriers for imaging and improved drug release.

In this work, a 'dual-key-and-lock' drug carrier was designed to respond to the tumor microenvironment (TME). A core-shell Fe-MOF@ZIF-8 was synthesized, with ZIF-8 as the shell (the first lock) to encapsulate catalase (CAT), and the Fe metal-organic framework (MOF) as the core (the second lock) to encapsulate the anticancer drug doxorubicin (DOX). Fe-MOF@ZIF-8 takes advantage of the TME-which includes a high concentration of H2O2, a weakly acidic environment and hypoxia-to achieve efficient cancer therapy. With the pH response, ZIF-8 and Fe-MOF are degraded in turn to release CAT and DOX, just like 'pH stimulation', as a key to open the two locks in turn. The released CAT reacts with the rich H2O2 in the tumor to produce O2 to regulate hypoxia, thereby improving the anticancer efficiency of the released DOX. The different cytotoxicity to L-02 cells and HeLa cells of Fe-MOF@ZIF-8 shows Fe-MOF@ZIF-8 is only harmful to cancer cells and is not harmful to normal cells. The reason is that the Fe2+/Fe3+ in Fe-MOF interact with the rich H2O2 in cancer cells to generate hydroxyl radicals (cOH), which is proved by the color of the solution of 3,3',5,5'-tetramethylbenzidine turning blue. After loading of the drug and CAT, Fe-MOF@ZIF-8 can release CAT, DOX and cOH in response to the TME, thus killing more HeLa cells. Therefore, synthesis of 'dual-key-and-lock' drug carriers responsive to the TME is a promising strategy for cancer treatment.

Low-dose phloretin alleviates diabetic atherosclerosis through endothelial KLF2 restoration.

We investigated whether low-dose phloretin served as daily dietary supplements could ameliorate diabetic atherosclerosis and the role of kruppel-like factor 2 (KLF2). HUVECs cultured in high glucose medium were treated with different concentrations of phloretin and KLF2 mRNA, and protein level was detected. Diabetes was induced using streptozotocin in Apoe-/- mice after which they were fed a high-cholesterol diet for 8 weeks. Diabetic mice injected with KLF2 shRNA-lentivirus or control virus were treated with 20 mg/kg phloretin. Glucose, lipid profile, aortic atheroma, and endothelial nitric oxide synthase (eNOS) expression were detected. Phloretin retained endothelial function by KLF2-eNOS activation under hyperglycemia. Low-dose phloretin helped with lipid metabolism, and blocked the acceleration of atherosclerosis in STZ-induced diabetic mice since the early stage, which was diminished by KLF2 knockdown. Low-dose phloretin exhibited athero-protective effect in diabetic Apoe-/- mice dependent on KLF2 activation. This finding makes phloretin for diabetic atherosclerosis.

Overexpression of lncRNA Gm2691 attenuates apoptosis and inflammatory response after myocardial infarction through PI3K/Akt signaling pathway.

Acute myocardial infarction is one of the most threatening disease in the world. In previous studies, numerous dysregulated lncRNAs exposed to ischemic reperfusion injury have been identified. In this differential lncRNAs, Gm2691 attracted our attention due to its high fold change. The aim of the study was to investigate the function and mechanism of lncRNA Gm2691 in ischemic reperfusion injury. AnaeroPack anaerobic system treated neonatal rat ventricular cardiomyocytes were used to analyze the function of lncRNA Gm2691 in vitro. Tunel, Caspase3, and inflammation markers were detected to evaluate apoptosis and inflammatory response. Rat acute myocardial infarction was performed to elucidate the function of lncRNA Gm2691 in vivo. The results showed that LncRNA Gm2691 improved the cardiac function and attenuated the inflammatory response in vivo. We also found that lncRNA Gm2691 reduced the apoptosis and improved cell survival rates in anaeroPack anaerobic system treated neonatal rat ventricular cardiomyocytes. Western blot analysis revealed that lncRNA Gm2691 decreased Akt and ERK1/2 activities, suggesting that lncRNA Gm2691 may functioned through Akt signaling pathway. We verified the function and mechanism of lncRNA Gm2691 and provide evidence that lncRNA Gm2691 may play important role in ischemic reperfusion injury, and understanding the precise role of Gm2691 will undoubtedly shed new light on the clinical treatment.