Insulin-like growth factor-1 in myocardial ischemia-reperfusion injury: A review.

Myocardial ischemia-reperfusion injury (MIRI) is a severe damage inflicted on the ischemic myocardium when blood flow is restored, and it commonly occurs in a wide range of cardiovascular diseases. Presently, no effective clinical treatment exists for MIRI. Accumulating evidence indicates that insulin-like growth factor-1 (IGF-1) plays a role in the intricate chain of cardiovascular events, in addition to its well-recognized growth-promoting and metabolic effects. IGF-1, a member of the insulin family, exhibits a broad spectrum of protective effects against ischemia/reperfusion injury in various tissues, especially the myocardium. In particular, earlier research has demonstrated that IGF-1 reduces cellular oxidative stress, improves mitochondrial function, interacts with noncoding RNAs, and activates cardiac downstream protective genes and protective signaling channels. This review aimed to summarize the role of IGF-1 in MIRI and elucidate its related mechanisms of action. In addition, IGF-1-related interventions for MIRI, such as ischemic preconditioning and post-conditioning, were discussed. The purpose of this review was to provide evidence supporting the activation of IGF-1 in MIRI and advocate its use as a therapeutic target.

Kaempferol and nicotiflorin ameliorated alcohol-induced liver injury in mice by miR-138-5p/SIRT1/FXR and gut microbiota.

Aims: Excessive alcohol consumption can lead to alcoholic liver diseases (ALDs). Tetrastigma hemsleyanum Diels et Gilg is a rare Chinese medicinal herb. Tetrastigma hemsleyanum Diels et Gilg has been validated to be highly effective for treating hepatitis. Kaempferol and nicotiflorin are two highly representative flavonoids, which have exhibit therapeutic effects on liver disease. Therefore, the protective mechanism of kaempferol and nicotiflorin on alcohol-induced liver injury were investigated. Main methods: Forty mice were used in this study. After treatment of Kaempferol and nicotiflorin, serum and liver were collected and used for determination of biochemical indicators, H&E staining, and molecular detection. The interaction of miRNAs from serum extracellular vehicles (EVs) with mRNAs and 16S rRNA sequencing of gut microbiota were also investigated. Key findings: The results showed that kaempferol and nicotiflorins significantly ameliorated alcohol-induced liver damage and observably regulated gut microbiota. Specifically, the levels of malondialdehyde (MDA) and CYP2E1 in the liver significantly reduced, and the activity of superoxide dismutase (SOD) and glutathione (GSH) in the liver evidently increased. They also significantly relieved liver oxidative stress and lipid accumulation by suppressing miR-138-5p expression, inversely enhancing deacetylase silencing information regulator 2 related enzyme-1 (SIRT1) levels and then decreasing farnesoid X receptor (FXR) acetylation, which then modulated Nrf2 and SREBP-1c signaling pathways to regulate oxidative stress and lipid metabolism induced by alcohol. Significance: Kaempferol and nicotiflorin reduced alcohol-induced liver damage by enhancing alcohol metabolism and reducing oxidative stress and lipid metabolism. The intestinal microorganism disorder was also ameliorated after oral kaempferol and nicotiflorin.

TTK inhibition activates STING signal and promotes anti-PD1 immunotherapy in breast cancer.

Despite progress in the application of checkpoint immunotherapy against various tumors, attempts to utilize immune checkpoint blockade (ICB) agents in triple negative breast cancer (TNBC) have yielded limited clinical benefits. The low overall response rate of checkpoint immunotherapy in TNBC may be attributed to the immunosuppressive tumor microenvironment (TME). In this study, we investigated the role of mitogen-associated kinase TTK in reprogramming immune microenvironment in TNBC. Notably, TTK inhibition by BAY-1217389 induced DNA damage and the formation of micronuclei containing dsDNA in the cytosol, resulting in elicition of STING signal pathway and promoted antitumor immunity via the infiltration and activation of CD8+ T cells. Moreover, TTK inhibition also upregulated the expression of PD-L1, demonstrating a synergistic effect with anti-PD1 therapy in 4T1 tumor-bearing mice. Taken together, TTK inhibition facilitated anti-tumor immunity mediated by T cells and enhanced sensitivity to PD-1 blockade, providing a rationale for the combining TTK inhibitors with immune checkpoint blockade in clinical trials.

Mushrooms Adapted to Seawater: Two New Species of Candolleomyces (Basidiomycota, Agaricales) from China.

Marine fungi have been studied for a long history in many realms, but there are few reports on marine mushrooms. In this study, marine fungi with conspicuous subglobose sequestrate basidioma were discovered from mangrove forests in South China. They grow on the deadwood of mangroves in the intertidal zone, periodically submerging into seawater due to the tide. Some marine animals were observed to nest in their basidiomata or consume them as food. The pileus-gleba-inner veil complex (PGI) of the basidioma was observed to be detached from the stipe and transferred into seawater by external forces, and drifting on sea to spread spores after maturity. The detachment mechanism of their PGIs was revealed through detailed microscopic observations. The contrast culturing experiment using freshwater and seawater potato dextrose agar media showed they have probably obligately adapted to the marine environment. Based on morphological and molecular phylogenetic evidence, two new species of Candolleomyces (Basidiomycota, Agaricales), namely C. brunneovagabundus and C. albovagabundus, were described. They are similar and close to each other, but can be distinguished by the size and color of the basidioma, and the size of the basidiospores.

Fingerprinting and source identification of an oil spill in China Bohai Sea by gas chromatography-flame ionization detection and gas chromatography-mass spectrometry coupled with multi-statistical analyses.

This paper describes a case study in which advanced chemical fingerprinting and data interpretation techniques were used to characterize the chemical composition and determine the source of an unknown spilled oil reported on the beach of China Bohai Sea in 2005. The spilled oil was suspected to be released from nearby platforms. In response to this specific site investigation need, a tiered analytical approach using gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detection (GC-FID) was applied. A variety of diagnostic ratios of "source-specific marker" compounds, in particular isomers of biomarkers, were determined and compared. Several statistical data correlation analysis methods were applied, including clustering analysis and Student's t-test method. The comparison of the two methods was conducted. The comprehensive analysis results reveal the following: (1) The oil fingerprinting of three spilled oil samples (S1, S2 and S3) positively match each other; (2) The three spilled oil samples have suffered different weathering, dominated by evaporation with decrease of the low-molecular-mass n-alkanes at different degrees; (3) The oil fingerprinting profiles of the three spilled oil samples are positive match with that of the suspected source oil samples C41, C42, C43, C44 and C45; (4) There are significant differences in the oil fingerprinting profiles between the three spilled oil samples and the suspected source oil samples A1, B1, B2, B3, B4, C1, C2, C3, C5 and C6.

[Identification of crude oils in Bohai Sea by polycyclic aromatic hydrocarbon fingerprinting].

Crude oils from different sources have quite different polycyclic aromatic hydrocarbon (PAH) distributions. Also, many PAH compounds are more resistant to weathering than their saturated counterparts (n-alkanes and isoprenoids) and volatile alkylbenzene compounds, thus PAils become one of the most valuable classes of hydrocarbons for oil identification using fingerprinting. A reliable, effective, and accurate gas chromatography/mass spectrometry (GC/MS) method for the differentiation and source identification of crude oils by the use of PAH compounds is described. PAll components of 6 crude oil samples from 5 different platforms in 4 different oil fields in Bohal Sea were analyzed by GC/MS. Using different methods, such as the comparisons of original fingerprinting, characteristic information, and diagnostic ratios of PAHs, 6 crude oil samples were identified completely, which showed distinctive characteristics of the same platform oils. Although distinction was diminutive, it can still be identified by GC/MS. PAHs could be used in weathering check of spilled oils in identification and to ensure the correctness of the identification.

Stearic acid protects primary cultured cortical neurons against oxidative stress.

AIM: To observe the effects of stearic acid against oxidative stress in primary cultured cortical neurons. METHODS: Cortical neurons were exposed to glutamate, hydrogen peroxide (H2O2), or NaN3 insult in the presence or absence of stearic acid. Cell viability of cortical neurons was determined by MTT assay and LDH release. Endogenous antioxidant enzymes activity[superoxide dismutases (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT)] and lipid peroxidation in cultured cortical neurons were evaluated using commercial kits. {3-[1(p-chlorobenzyl)- 5-(isopropyl)-3-t-butylthiondol-2-yl]-2,2-dimethylpropanoic acid, Na} [MK886; 5 micromol/L; a noncompetitive inhibitor of proliferator-activated receptor (PPAR) alpha], bisphenol A diglycidyl ether (BADGE; 100 micromol/L; an antagonist of PPAR gamma), and cycloheximide (CHX; 30 micromol/L, an inhibitor of protein synthesis) were tested for their effects on the neuroprotection afforded by stearic acid. Western blotting was used to determine the PPAR gamma protein level in cortical neurons. RESULTS: Stearic acid dose-dependently protected cortical neurons against glutamate or H2O2 injury and increased glutamate uptake in cultured neurons. This protection was concomitant to the inhibition of lipid peroxidation and to the promotion activity of Cu/Zn SOD and CAT in cultured cortical neurons. Its neuroprotective effects were completely blocked by BADGE and CHX. After incubation with H2O2 for 24 h, the expression of the PPAR gamma protein decreased significantly (P<0.05), and the inhibitory effect of H2O2 on the expression of PPAR gamma can be attenuated by stearic acid. CONCLUSION: Stearic acid can protect cortical neurons against oxidative stress by boosting the internal antioxidant enzymes. Its neuroprotective effect may be mainly mediated by the activation of PPAR gamma and new protein synthesis in cortical neurons.

Neuroprotective effects of arachidonic acid against oxidative stress on rat hippocampal slices.

Arachidonic acid (AA), 5,8,11,14-eicosateraenoic acid is abundant, active and necessary in the human body. In the present study, we reported the neuroprotective effects and mechanism of arachidonic acid on hippocampal slices insulted by glutamate, NaN(3) or H(2)O(2)in vitro. Different types of models of brain injury in vitro were developed by 1mM glutamate, 10mM NaN(3) or 2mM H(2)O(2). After 30 min of preincubation with arachidonic acid or linoleic acid, hippocampal slices were subjected to glutamate, NaN(3) or H(2)O(2), then the tissue activities were evaluated by using the 2,3,5-triphenyltetrazolium chloride method. Endogenous antioxidant enzymes activities (SOD, GSH-PX and catalase) in hippocampal slices were evaluated during the course of incubation. MK886 (5 microM; a noncompetitive inhibitor of proliferator-activated receptor [PPAR]alpha), BADGE (bisphenol A diglycidyl ether; 100 microM; an antagonist of PPARgamma) and cycloheximide (CHX; 30 microM; an inhibitor of protein synthesis) were tested for their effects on the neuroprotection afforded by arachidonic acid. Population spikes were recorded in randomly selected hippocapal slices. Arachidonic acid (1-10 microM) dose dependently protected hippocampal slices from glutamate and H(2)O(2) injury (P<0.01), and arachidonic acid (10 microM) can significantly improve the activities of Cu/Zn-SOD in hippocampal slices after 1h incubation. In addition, 10 microM arachidonic acid significantly increased the activity of Mn-SOD and catalase, and decreased the activities of Cu/Zn-SOD to control value after 3h incubation. These secondary changes of SOD during incubation can be reversed by indomethacine (10 microM; a nonspecific cyclooxygenase inhibitor) or AA 861 (20 microM; a 5-lipoxygenase inhibitor). Its neuroprotective effect was completely abolished by BADGE and CHX. These observations reveal that arachidonic acid can defense against oxidative stress by boosting the internal antioxidant system of hippocampal slices. Its neuroprotective effect may be mainly mediated by the activation of PPARgamma and synthesis of new protein in tissue.

Neuroprotective effect of the stearic acid against oxidative stress via phosphatidylinositol 3-kinase pathway.

Stearic acid is a long-chain saturated fatty acid consisting of 18 carbon atoms without double bonds. In the present study, we reported the neuroprotective effects and mechanism of stearic acid on cortical or hippocampal slices insulted by oxygen-glucose deprivation, NMDA or hydrogen peroxide (H(2)O(2)) in vitro. Different types of models of brain slice injury in vitro were developed by 10 min of oxygen/glucose deprivation, 0.5 mM NMDA or 2 mM H(2)O(2), respectively. After 30 min of preincubation with stearic acid (3-30 microM), cortical or hippocampal slices were subjected to oxygen-glucose deprivation, NMDA or H(2)O(2). Then the tissue activities were evaluated by using the 2,3,5-triphenyltetrazolium chloride (TTC) method. Population spikes were recorded in randomly selected hippocampal slices. Stearic acid (3-30 microM) dose-dependently protected brain slices from oxygen-glucose deprivation, NMDA and H(2)O(2) insults. Its neuroprotective effect against H(2)O(2) insults can be completely blocked by wortmannin (inhibitor of PI3K) and partially blocked by H7 (inhibitor of PKC) or genistein (inhibitor of TPK). Treatment of cortical or hippocampal slices with 30 microM stearic acid resulted in a significant increase in PI3K activity at 5, 10, 30 and 60 min. These observations reveal that stearic acid can protect cortical or hippocampal slices against injury induced by oxygen-glucose deprivation, NMDA or H(2)O(2), and its neuroprotective effects are via phosphatidylinositol 3-kinase dependent mechanism.

Neuroprotective effects of stearic acid against toxicity of oxygen/glucose deprivation or glutamate on rat cortical or hippocampal slices.

AIM: To observe the effects of stearic acid, a long-chain saturated fatty acid consisting of 18 carbon atoms, on brain (cortical or hippocampal) slices insulted by oxygen-glucose deprivation (OGD), glutamate or sodium azide (NaN3) in vitro. METHODS: The activities of hippocampal slices were monitored by population spikes recorded in the CA1 region. In vitro injury models of brain slice were induced by 10 min of OGD, 1 mmol/L glutamate or 10 mmol/L NaN3. After 30 min of pre-incubation with stearic acid (3-30 micromol/L), brain slices (cortical or hippocampal) were subjected to OGD, glutamate or NaN3, and the tissue activities were evaluated by using the 2,3,5-triphenyltetrazolium chloride method. MK886 [5 mmol/L; a noncompetitive inhibitor of proliferator-activated receptor (PPAR-alpha)] or BADGE (bisphenol A diglycidyl ether; 100 micromol/L; an antagonist of PPAR-gamma) were tested for their effects on the neuroprotection afforded by stearic acid. RESULTS: Viability of brain slices was not changed significantly after direct incubation with stearic acid. OGD, glutamate and NaN3 injury significantly decreased the viability of brain slices. Stearic acid (3-30 micromol/L) dose-dependently protected brain slices from OGD and glutamate injury but not from NaN3 injury, and its neuroprotective effect was completely abolished by BADGE. CONCLUSION: Stearic acid can protect brain slices (cortical or hippocampal) against injury induced by OGD or glutamate. Its neuroprotective effect may be mainly mediated by the activation of PPAR-gamma.