Myocardial Ischemia/Reperfusion Injury: Mechanism and Targeted Treatment for Ferroptosis.

Myocardial ischemia/reperfusion injury (MIRI) is a pathophysiological process connected to the onset of numerous heart disorders. The pathogenesis of MIRI is complex, and it mainly involves calcium overload, classic oxidative stress, mitochondrial disorder, inflammation, microvascular disorder, and cell death. The clinical treatment options for MIRI are presently constrained, making it imperative to develop new treatment modalities. Recent studies have demonstrated that ferroptosis is the main cause of MIRI. Ferroptosis is a new type of regulated iron-dependent cell death whose mechanism and targeted therapy are anticipated to be novel therapeutic techniques for MIRI. Herein, the primary mechanism underlying ferroptosis (the 3 major metabolic routes involving iron, amino acids, and lipids, and in MIRI, the specific mechanism and therapeutic target of ferroptosis) are discussed to determine the potential therapeutic approach for MIRI.

Immuno-protective effect of neuropeptide Y immersion on the juvenile tilapia infected by Streptococcus agalactiae.

Neuropeptide Y (NPY), an important neurotransmitter, is widely distributed in the nervous systems of vertebrates. Multiple functions of NPY in mammals include the regulation of brain activity, emotion, stress response, feeding, digestion, metabolism and immune function. In the present study, we used synthetic NPY to immerse juvenile tilapia, thus firstly exploring the dose and time effect of this immersion. The results showed that the expression level of y8b and serum glucose increased after NPY immersion. When juvenile tilapia was challenged with Streptococcus agalactiae (S. agalactiae), no matter before or after the administration of NPY-immersion, it was found that NPY immersion could inhibit the expression of il-1ß induced by S. agalactiae in telencephalon, hypothalamus, spleen and head kidney, and then promote the expression of il-10. In addition, NPY-immersion could reduce the activity of serum SOD but increase that of lysozyme, and ameliorate tissue damage in the head kidney and spleen of juvenile tilapia caused by S. agalactiae infection. This study firstly proposes the potential of NPY to be an immune protect factor in juvenile fish, and the results can provide a reference for the application of immersion administration in the immune protection of juvenile fish.

Metabolic changes of Issatchenkia orientalis under acetic acid stress by transcriptome profile using RNA-sequencing / Cambios metabólicos de Issatchenkia orientalis bajo estrés con ácido acético por perfil de transcriptoma usando secuenciación de ARN

Issatchenkia orientalis (I. orientalis) is tolerant to various environmental stresses especially acetic acid stress in wine making. However, limited literature is available on the transcriptome profile of I. orientalis under acetic acid stress. RNA-sequence was used to investigate the metabolic changes due to underlying I. orientalis 166 (Io 166) tolerant to acetic acid. Transcriptomic analyses showed that genes involved in ergosterol biosynthesis are differentially expressed under acetic acid stress. Genes associated with ribosome function were downregulated, while energy metabolism-related genes were upregulated. Moreover, Hsp70/Hsp90 and related molecular chaperones were upregulated to recognize and degrade misfolded proteins. Compared to Saccharomyces cerevisiae, transcriptomic changes of Io 166 showed many similarities under acetic acid stress. There were significant upregulation of genes in ergosterol biosynthesis and for the application of wine production.(AU)

Structural integrity is essential for the protective effect of mitochondrial transplantation against UV-induced cell death.

Mitochondrial transplantation (MT) is a new technology developed in recent years, which injects healthy mitochondria directly into damaged tissues or blood vessels to play a therapeutic role. This technology has been studied in many animal models of various diseases including myocardial ischemia, cerebral stroke, liver and lung injury, and even has been successfully used in the treatment of childhood heart disease. MT can quickly improve tissue function within a few minutes after injection. The speed with which MT improves tissue function is frequently questioned, for it is hard to understand how the whole mitochondrion transports to the damaged sites, enters cells and functions within such a short period of time. Are there small molecules of mitochondrial component responsible for the function of MT? To test this hypothesis, we established an ultra-violet (UV)-irradiated HeLa cell model. The results of colony formation, sulforhodamine B (SRB), and Hoechst 33342/PI double staining assay strongly indicated that MT exhibited a significant protective effect against UV irradiation damage. The UV irradiation-induced cell cycle arresting at S phase, apoptosis, mitochondrial membrane potential (MMP) decreasing, and the related apoptosis signaling factors p-IKKα, p-p65, I-κB and the activation of caspase3 were all reversed by MT treatments to some extent. The mechanisms of MT were evaluated through comparing the effect of thermal inactivation, ultrasonic crushing, and repeated freezing and thawing treatments on MT function. These results denied the above hypothesis that mitochondrial component may be responsible for MT, excluded the function of ATP, mtDNA and other small molecules, and indicated that the mitochondria structural integrity is essential. We also evaluated the effect of Ca2+ concentrations (1 and 1.8 mM) on MT, and the results showed no effect was found in this UV-irradiated HeLa cell model. Our data support a potent anti-UV irradiation effect of MT, and that structural integrity of the mitochondria is critical for its function.

Metabolic changes of Issatchenkia orientalis under acetic acid stress by transcriptome profile using RNA-sequencing.

Issatchenkia orientalis (I. orientalis) is tolerant to various environmental stresses especially acetic acid stress in wine making. However, limited literature is available on the transcriptome profile of I. orientalis under acetic acid stress. RNA-sequence was used to investigate the metabolic changes due to underlying I. orientalis 166 (Io 166) tolerant to acetic acid. Transcriptomic analyses showed that genes involved in ergosterol biosynthesis are differentially expressed under acetic acid stress. Genes associated with ribosome function were downregulated, while energy metabolism-related genes were upregulated. Moreover, Hsp70/Hsp90 and related molecular chaperones were upregulated to recognize and degrade misfolded proteins. Compared to Saccharomyces cerevisiae, transcriptomic changes of Io 166 showed many similarities under acetic acid stress. There were significant upregulation of genes in ergosterol biosynthesis and for the application of wine production.

Integrated transcriptomic and proteomic analysis of the acetic acid stress in Issatchenkia orientalis.

Issatchenkia orientalis known as a multi-tolerant non-Saccharomyces yeast, which tolerant environmental stresses, exhibits potential in wine making and bioethanol production. It is essential for the growth of I. orientalis to tolerant acetic acid in the mixed cultures with Saccharomyces cerevisiae. In this work, RNA-sequence and TMT (Tandem Mass Tag) were used to examine the comprehensive transcriptomic and proteomic profiles of I. orientalis in response to acetic acid. The results showed that 876 genes were identified differentially transcribed in I. orientalis genome and 399 proteins expressed in proteome after 4 hr acetic acid (90 mM, pH 4.5). The comprehensive analysis showed a series of determinants of acetic acid tolerance: Glycolysis and TCA cycle provide enough nicotinamide adenine dinucleotide to effectively convert acetic acid. Genes associated with potassium, iron, zinc, and glutathione synthesis were upregulated. The same changes of differentially expressed genes and proteins were mainly concentrated in chaperones, coenzyme, energy production, and transformation. PRACTICAL APPLICATIONS: In addition to the main fermentation products, wine yeast also produces metabolite acetic acid in the fermentation process, and yeast cells are exposed to acetic acid stress, which restrains cell proliferation. Issatchenkia orientalis exhibits great potential in winemaking and bioethanol production. The yeast is known as a multi-tolerant non-Saccharomyces yeast that can tolerate a variety of environmental stresses. In this study, RNA-Seq and TMT were conducted to investigate the changes in transcriptional and proteomic profile of I. orientalis under acetic acid stress. The knowledge of the transcription and expression changes of the I. orientalis is expected to understand the tolerance mechanisms in I. orientalis and to guide traditional fermentation processes by Saccharomyces cerevisiae improving its high resistance to acetic acid stress.

Potential of Immune-Related Therapy in COVID-19.

At the beginning of 2020, a sudden outbreak of new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infections led to anxiety, panic, and crisis among people worldwide. The outbreak first occurred in Wuhan, China, in late December 2019 and then spread rapidly across the globe, thus becoming a major public health emergency. Although the current epidemic situation in China tends to be stable, coronavirus disease 2019 (COVID-19) continues to spread globally. At present, no specific therapeutic drugs and vaccines are available against COVID-19. Also, the pathogenesis of the SARS-CoV-2 is not fully clear. Human immunity is important in SARS-CoV-2 infection. Studies have shown that excessive inflammation caused by SARS-CoV-2 infection and subsequent induced uncontrolled cytokine storm are the main causes of disease deterioration and death of severe patients. Therefore, immune-related research is of great significance for the prevention, control, and prognosis of COVID-19. This study aimed to review the latest research on immune-related treatment of COVID-19.

Integrated transcriptomic and proteomic analysis of the ethanol stress response in Saccharomyces cerevisiae Sc131.

The molecular mechanism of Saccharomyces cerevisiae tolerant to ethanol stress remains to be further elucidated. In this study, a comprehensive analysis based on RNA-seq and iTRAQ LC-MS/MS was used to investigate the global mechanism of S. cerevisiae strain Sc131 in response to ethanol stress at transcriptomic and proteomic levels. Totally, 937 differentially expressed genes (DEGs) and 457 differentially expressed proteins (DEPs) were identified in Sc131 under ethanol stress. Results revealed that 4-h ethanol stress (10% v/v) can induce filamentous growth, sexual reproduction. Mitochondria and endoplasmic reticulum (ER) were proved to be two important organelles in resisting ethanol stress. Signal transduction such as G-protein coupled receptor signaling and metal ion regulation were remarkably activated at the presence of ethanol. Moreover, silent information regulator (Sir) proteins and aromatic amino acids especially tryptophan were involved in response to ethanol and might be helpful for cell survival. This study provides a global perspective on the mechanism of S. cerevisiae tolerant to ethanol stress and sheds light on the potential application of Sc131 in Chinese bayberry wine brewing. BIOLOGICAL SIGNIFICANCE: It is of great importance for S. cerevisiae to tolerate high levels of ethanol during wine fermentation. However, the molecular mechanism of S. cerevisiae tolerant to ethanol stress remains to be further elucidated at transcriptomic and proteomic levels. In present study, we employed a comprehensive analysis based on RNA-seq and iTRAQ and found several potential pathways involving in the response of Sc131 to ethanol stress. To our knowledge, this is the first integrated analysis combining transcriptomic and proteomic technologies to study the mechanism of Sc131 under ethanol stress.

Transcriptome profiling of Issatchenkia orientalis under ethanol stress.

Issatchenkia orientalis, a non-Saccharomyces yeast that can resist a wide variety of environmental stresses, has potential use in winemaking and bioethanol production. Little is known about gene expression or the physiology of I. orientalis under ethanol stress. In this study, high-throughput RNA sequencing was used to investigate the transcriptome profile of I. orientalis in response to ethanol. 502 gene transcripts were differentially expressed, of which 451 were more abundant, and 51 less abundant, in cells subjected to 4 h of ethanol stress (10% v/v). Annotation and statistical analyses suggest that multiple genes involved in ergosterol biosynthesis, trehalose metabolism, and stress response are differentially expressed under these conditions. The up-regulation of molecular chaperones HSP90 and HSP70, and also genes associated with the ubiquitin-proteasome proteolytic pathway suggests that ethanol stress may cause aggregation of misfolded proteins. Finally, ethanol stress in I. orientalis appears to have a nitrogen starvation effect, and many genes involved in nutrient uptake were up-regulated.

Investigating the underlying mechanism of Saccharomyces cerevisiae in response to ethanol stress employing RNA-seq analysis.

Saccharomyces cerevisiae has been widely used for wine fermentation and bio-fuels production. A S. cerevisiae strain Sc131 isolated from tropical fruit shows good fermentation properties and ethanol tolerance, exhibiting significant potential in Chinese bayberry wine fermentation. In this study, RNA-sequence and RT-qPCR was used to investigate the transcriptome profile of Sc131 in response to ethanol stress. Scanning Electron Microscopy were carried out to observe surface morphology of yeast cells. Totally, 937 genes were identified differential expressed, including 587 up-regulated and 350 down-regulated genes, after 4-h ethanol stress (10% v/v). Transcriptomic analysis revealed that, most genes involved in regulating filamentous growth or pseudohyphal growth were significantly up-regulated in response to ethanol stress. The complex protein quality control machineries, Hsp90/Hsp70 and Hsp104/Hsp70/Hsp40 based chaperone system combining with ubiquitin-proteasome proteolytic pathway were both activated to recognize and degrade misfolding proteins. Genes related to biosynthesis and metabolism of two well-known stress-responsive substances trehalose and ergosterol were generally up-regulated, while genes associated with amino acids biosynthesis and metabolism processes were differentially expressed. Moreover, thiamine was also important in response to ethanol stress. This research may promote the potential applications of Sc131 in the fermentation of Chinese bayberry wine.