Adenosine Triphosphate Content Research Articles

Electric field coupled with Fe3O4 modified biochar to enhance anaerobic degradation of phenolic compounds in coal gasification wastewater (CGW)

Anaerobic treatment of coal gasification wastewater is usually limited by the inhibition of high concentration of phenolics. In this study, the Fe3O4 loaded biochar (FeBC) coupled with electric field (E-FB) was used to enhance anaerobic phenolics degradation. E-FB significantly accelerated anaerobic removal of phenol, p-cresol and 3,5-xylenol with methane production improved by 84.2 % compared to the control, where FeBC contributed most. E-FB improved anodic oxidation capacity, adsorption-biodegradation and Fe (III) reduction process, which resulted from the synergistic effects between electric field and FeBC. E-FB significantly enhanced the microbial activity and extracellular electron transfer (EET) in the suspended sludge with the maximum electron transfer system activity (132.9 %), cytochrome C (7.2 nmol/g MLSS) and adenosine triphosphate contents (87.8 nmol/ g MLSS) obtained. Compared with FB, E-FB stimulated the secretion of proteins and humic acid-like substances in extracellular polymeric substance, which could contribute to higher EET efficiency. More abundant phenol degrading bacteria, dissimilatory iron reducing bacteria, electroactive bacteria and potential direct interspecies electron transfer (DIET) partners (e.g., Geobacter and Methanobacterium) were enriched in E-FB especially on the anode. The benzoyl-CoA pathway on the anode and CO2-reduction methanogenesis (possibly via DIET) in the suspended sludge and anode were improved in E-FB.

New Tiaoxin Recipe Alleviates Energy Metabolism Disorders in an APPswe/PS1DE9 Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a typical neurodegenerative disease with a complex etiology. Until now, there has been no effective treatment available for AD; however, improving energy dysmetabolism, the key pathological event in the early stage of AD, can effectively delay the progression of AD. This paper aims to investigate the therapeutic effect and potential mechanism of the new Tiaoxin recipe on early AD. APP/PS1 mice were divided into a model group, a new Tiaoxin recipe group, and a donepezil group, and C57/BL mice were used for the control group. Mouse cognitive and learning abilities were tested using the Morris water maze test and a new object-recognition experiment. The 42 amino acid form of amyloid β peptide (Aβ1-42) content was detected by enzyme-linked immunosorbent assay, the senile plaque area was detected by thioflavin S staining, and the senescence- associated β-galactosidase (SA-β-gal)-positive area was detected by chemical staining. Also, the adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD+), and nicotinamide adenine dinucleotide hydride (NADH) contents were detected using a biochemical method, and the cluster of differentiation 38 (CD38) and silent mating-type information regulation 2 homolog 3 (SIRT3) protein expression levels were detected by immunofluorescence and Western blot analysis. Compared with those of the control group, the learning and memory abilities of the model group were impaired; the senile plaque deposition, Aβ1-42 content, and SA-βgal-positive staining area were increased; the ATP concentration, NAD+ concentration, and NAD+/NADH ratio were decreased; the CD38 protein expression level was increased; and the SIRT3 protein expression level was decreased. Following intervention with the new Tiaoxin recipe, the learning and memory abilities were improved; the senile plaque deposition, Aβ1-42 content, and SA-βgal-positive area were reduced; the ATP concentration, NAD+ concentration, and NAD+/NADH ratio were increased; CD38 protein expression was decreased, and SIRT3 protein expression was increased. This study shows that the new Tiaoxin Recipe can improve cognitive ability and reduce the Aβ1-42 content and senile plaque deposition in APP/PS1 mice, which may occur through the downregulation of CD38 protein expression, upregulation of SIRT3 protein expression, restoration of the NAD+ level, promotion of ATP synthesis, mitigation of energy metabolism disorders.

Silencing KLF6 Alleviates Cigarette Smoke Extract-Induced Mitochondrial Dysfunction in Bronchial Epithelial Cells by SIRT4 Upregulation.

The incidence of chronic obstructive pulmonary disease (COPD) is increasing year by year. Kruppel-like factor 6 (KLF6) plays an important role in inflammatory diseases. However, the regulatory role of KLF6 in COPD has not been reported so far. The viability of human bronchial epithelial cells BEAS-2B induced by cigarette smoke extract (CSE) was detected by CCK-8 assay. The protein expression of KLF6 and sirtuin 4 (SIRT4) was appraised with Western blot. RT-qPCR and Western blot were applied to examine the transfection efficacy of sh-KLF6 and Oe-KLF6. Cell apoptosis was detected using flow cytometry. The levels of inflammatory factors IL-6, TNF-α and IL-1β were assessed with ELISA assay. DCFH-DA staining was employed for the detection of ROS activity and the levels of oxidative stress markers SOD, CAT and MDA were estimated with corresponding assay kits. The mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content and Complex I activity were evaluated with JC-1 staining, ATP colorimetric/fluorometric assay kit and Complex I enzyme activity microplate assay kit. With the application of mitochondrial permeability transition pore detection kit, mPTP opening was measured. Luciferase report assay was employed to evaluate the activity of SIRT4 promoter and chromatin immunoprecipitation (ChIP) to verify the binding ability of KLF6 and SIRT4 promoter. KLF6 expression was significantly elevated in CSE-induced cells. KLF6 was confirmed to suppress SIRT4 transcription. Interference with KLF6 expression significantly inhibited cell viability damage, cell apoptosis, inflammatory response, oxidative stress and mitochondrial dysfunction in CSE-induced BEAS-2B cells, which were all reversed by SIRT4 overexpression. Silencing KLF6 alleviated CSE-induced mitochondrial dysfunction in bronchial epithelial cells by SIRT4 upregulation.

Red Blood Cell Adenylate Energetics Is Related to Endothelial and Microvascular Function in Long COVID.

Adenine nucleotides play a critical role in maintaining essential functions of red blood cells (RBCs), including energy metabolism, redox status, shape fluctuations and RBC-dependent endothelial and microvascular functions. Recently, it has been shown that infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) might lead to morphological and metabolic alterations in erythrocytes in both mild and severe cases of coronavirus disease (COVID-19). However, little is known about the effects of COVID-19 on the nucleotide energetics of RBCs nor about the potential contribution of nucleotide metabolism to the long COVID syndrome. This study aimed to analyze the levels of adenine nucleotides in RBCs isolated from patients 12 weeks after mild SARS-CoV-2 infection who suffered from long COVID symptoms and to relate them with the endothelial and microvascular function parameters as well as the rate of peripheral tissue oxygen supply. Although the absolute quantities of adenine nucleotides in RBCs were rather slightly changed in long COVID individuals, many parameters related to the endothelial and microcirculatory function showed significant correlations with RBC adenosine triphosphate (ATP) and total adenine nucleotide (TAN) concentration. A particularly strong relationship was observed between ATP in RBCs and the serum ratio of arginine to asymmetric dimethylarginine-an indicator of endothelial function. Consistently, a positive correlation was also observed between the ATP/ADP ratio and diminished reactive hyperemic response in long COVID patients, assessed by the flow-mediated skin fluorescence (FMSF) technique, which reflected decreased vascular nitric oxide bioavailability. In addition, we have shown that patients after COVID-19 have significantly impaired ischemic response parameters (IR max and IR index), examined by FMSF, which revealed diminished residual bioavailability of oxygen in epidermal keratinocytes after brachial artery occlusion. These ischemic response parameters revealed a strong positive correlation with the RBC ATP/ADP ratio, confirming a key role of RBC bioenergetics in peripheral tissue oxygen supply. Taken together, the outcomes of this study indicate that dysregulation of metabolic processes in erythrocytes with the co-occurring endothelial and microvascular dysfunction is associated with diminished intracellular oxygen delivery, which may partly explain long COVID-specific symptoms such as physical impairment and fatigue.

Nanoparticle drug delivery systems responsive to tumor microenvironment: Promising alternatives in the treatment of triple-negative breast cancer.

The conventional therapeutic treatment of triple-negative breast cancer (TNBC) is negatively influenced by the development of tumor cell drug resistant, and systemic toxicity of therapeutic agents due to off-target activity. In accordance with research findings, nanoparticles (NPs) responsive to the tumor microenvironment (TME) have been discovered for providing opportunities to selectively target tumor cells via active targeting or Enhanced Permeability and Retention (EPR) effect. The combination of the TME control and therapeutic NPs offers promising solutions for improving the prognosis of the TNBC because the TME actively participates in tumor growth, metastasis, and drug resistance. The NP-based systems leverage stimulus-responsive mechanisms, such as low pH value, hypoxic, excessive secretion enzyme, concentration of glutathione (GSH)/reactive oxygen species (ROS), and high concentration of Adenosine triphosphate (ATP) to combat TNBC progression. Concurrently, NP-based stimulus-responsive introduces a novel approach for drug dosage design, administration, and modification of the pharmacokinetics of conventional chemotherapy and immunotherapy drugs. This review provides a comprehensive examination of the strengths, limitations, applications, perspectives, and future expectations of both novel and traditional stimulus-responsive NP-based drug delivery systems for improving outcomes in the medical practice of TNBC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Sodium butyrate activates the KATP channels to regulate the mechanism of Parkinson's disease microglia model inflammation.

Parkinson's disease (PD) is a common neurodegenerative disorder. Microglia-mediated neuroinflammation has emerged as an involving mechanism at the initiation and development of PD. Activation of adenosine triphosphate (ATP)-sensitive potassium (KATP ) channels can protect dopaminergic neurons from damage. Sodium butyrate (NaB) shows anti-inflammatory and neuroprotective effects in some animal models of brain injury and regulates the KATP channels in islet β cells. In this study, we aimed to verify the anti-inflammatory effect of NaB on PD and further explored potential molecular mechanisms. We established an in vitro PDmodel in BV2 cells using 1-methyl-4-phenylpyridinium (MPP+ ). The effects of MPP+ and NaB on BV2 cell viability were detected by cell counting kit-8 assays. The morphology of BV2 cells with or without MPP+ treatment was imaged via an optical microscope. The expression of Iba-1 was examined by the immunofluorescence staining. The intracellular ATP content was estimated through the colorimetric method, and Griess assay was conducted to measure the nitric oxide production. The expression levels of pro-inflammatory cytokines and KATP channel subunits were evaluated by reverse transcription-quantitativepolymerase chain reaction and western blot analysis. NaB (5 mM) activated the KATP channels through elevating Kir6.1 and Kir6.1 expression in MPP+ -challenged BV2 cells. Both NaB and pinacidil (a KATP opener) suppressed the MPP+ -induced activation of BV2 cells and reduced the production of nitrite and pro-inflammatory cytokines in MPP+ -challenged BV2 cells. NaB treatment alleviates the MPP+ -induced inflammatory responses in microglia via activation of KATP channels.

Yinhuang granule alleviates carbon tetrachloride-induced liver fibrosis in mice and its mechanism.

Liver fibrosis is a formidable global medical challenge, with no effective clinical treatment currently available. Yinhuang granule (YHG) is a proprietary Chinese medicine comprising Scutellariae Radix and Lonicerae Japonicae Flos. It is frequently used for upper respiratory tract infections, pharyngitis, as well as acute and chronic tonsillitis. To investigate the potential of YHG in alleviating carbon tetrachloride (CCl4)-induced liver fibrosis in mice. To induce a hepatic fibrosis model in mice, this study involved intraperitoneal injections of 2 mL/kg of CCl4 twice a week for 4 wk. Meanwhile, liver fibrosis mice in the low dose of YHG (0.4 g/kg) and high dose of YHG (0.8 g/kg) groups were orally administered YHG once a day for 4 wk. Serum alanine/aspartate aminotransferase (ALT/AST) activity and liver hydroxyproline content were detected. Sirius red and Masson's trichrome staining assay were conducted. Real-time polymerase chain reaction, western-blot and enzyme-linked immunosorbent assay were conducted. Liver glutathione content, superoxide dismutase activity level, reactive oxygen species and protein carbonylation amount were detected. The administration of YHG ameliorated hepatocellular injury in CCl4-treated mice, as reflected by decreased serum ALT/AST activity and improved liver histological evaluation. YHG also attenuated liver fibrosis, evident through reduced liver hydroxyproline content, improvements in Sirius red and Masson's trichrome staining, and lowered serum hyaluronic acid levels. Furthermore, YHG hindered the activation of hepatic stellate cells (HSCs) and ameliorated oxidative stress injury and inflammation in liver from CCl4-treated mice. YHG prompted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated the expression of Nrf2-dependent downstream antioxidant genes. In addition, YHG promoted mitochondrial biogenesis in liver from CCl4-treated mice, as demonstrated by increased liver adenosine triphosphate content, mitochondrial DNA levels, and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and nuclear respiratory factor 1. YHG effectively attenuates CCl4-induced liver fibrosis in mice by inhibiting the activation of HSCs, reducing inflammation, alleviating liver oxidative stress damage through Nrf2 activation, and promoting liver mitochondrial biogenesis.

Effects of cations on biofilms in gravity-driven membrane system: Filtration performance and mechanism investigation

The gravity-driven membrane (GDM) system is desirable for energy-efficient water treatment. However, little is known about the influence of cations on biofilm properties and GDM performance. In this study, typical cations (Ca2+ and Na+) were used to reveal the combined fouling behavior and mechanisms. Results showed that Ca2+ improved the stable flux and pollutant removal efficiency, while Na+ adversely affected the flux. Compared with GDM control, the concentration of pollutants was lower in Ca-GDM, as indicated by the low biomass, proteins, and polysaccharides. A heterogeneous and loose biofilm was observed in the Ca-GDM system, with roughness and porosity increasing by 43.06 % and 32.60 %, respectively. However, Na+ induced a homogeneous and dense biofilm, with porosity and roughness respectively reduced by 17.48 % and 22.04 %. The richness of bacterial communities increased in Ca-GDM systems, while it decreased in Na-GDM systems. High adenosine triphosphate (ATP) concentration in Ca-GDM system was consistent with the abundant bacteria and their high biological activity, which was helpful for the efficient removal of pollutants. The abundance of Apicomplexa, Platyhelminthes, Annelida and Nematoda increased after adding Ca2+, which was related to the formation of loose biofilms. Computational simulations indicated that the free volumes of the biofilms in Ca-GDM and Na-GDM were 13.7 and 13.2 nm3, respectively. The addition of cations changed intermolecular forces, Ca2+ induced bridging effects led to large and loose floc particles, while the significant dehydration of hydrated molecules in the Na-GDM caused obvious aggregation. Overall, microbiological characteristics and contaminant molecular interactions were the main reasons for differences in GDM systems.

Изменение ИК-спектров метаболитов энергетического обмена в крови крыс с гепатоцеллюлярной карциномой при воздействии гипертермии и апитоксина

There is a need to develop and improve conservative treatment methods for malignant liver tumours, since only in a small percentage of cases (10–30 %) radical treatments can be applied. Therefore, of relevance are studies into the effect of hyperthermia on the absorption of antitumour drugs and the effect of bee venom as a physiological therapeutic agent on the energy metabolism of tumour cells. Infrared spectroscopy could potentially be used to study changes in energy metabolism parameters in the blood plasma. The purpose of this article is to assess changes in the concentrations of energy metabolism metabolites in the blood of tumour-bearing animals during hyperthermia under the action of apitoxin using infrared spectroscopy. Materials and methods. The research involved 50 white non-linear female rats, divided into an intact, control and three experimental groups. The control and experimental groups were inoculated with hepatocellular carcinoma. The experimental groups were injected intraperitoneally with honey bee venom followed by hyperthermia sessions at different temperatures (42.5; 43.5 and 44.5 °С). Blood plasma was studied using a spectrophotometer in the wavenumber range of 1170–1025 cm–1. Results. We found a statistically significant increase in adenosine triphosphate concentrations (by 54 %) and a decrease in adenosine monophosphate (by 54 %), adenosine diphosphate (by 18 %) and glucose (by 87 %) levels compared to the control at 42.5 °C hyperthermia under the action of bee venom by the 7th day; however, on the 28th day the opposite effect was observed: an increase in adenosine monophosphate, adenosine diphosphate and glucose concentrations and a decrease in adenosine triphosphate levels. No positive dynamic was detected at other hyperthermia regimens. It is concluded that infrared spectroscopy can be used to assess energy changes in animals with hepatocellular carcinoma at different hyperthermia regimens under the therapeutic effect of bee venom. The optimal conditions for bee venom effects on the body are achieved at 42.5 °C.

Energy Metabolism in Residents in the Low- and Moderate Altitude Regions of Central Asia with MAFLD and Type 2 Diabetes Mellitus.

The knowledge about the features of energy metabolism in MAFLD in the population living at different climatic and geographic heights is lacking. The goal of this study is to explore the biochemical parameters of blood and erythrocyte energy consumption in patients with MAFLD with and without DM2 living in the low- and moderate-altitude regions of Central Asia. Our study was carried out on patients living in low-altitude mountains: Bishkek, altitude=750-800 m; n=67 (MAFLD with DM 2: n=24; MAFLD without DM2: n=25; control: n=18), and At-Bashy District, Naryn Region, altitude=2046-2300 m; n=58 (MAFLD with DM2: n=28; MAFLD without DM2: n=18; control: n=12). Non-alcoholic fatty liver disease was diagnosed according to history, laboratory tests, liver ultrasound, and exclusion of other liver diseases. The level of liver fibrosis was determined using the FIB-4 score. Blood adenosine 5'-triphosphate (ATP) was determined using the CellTiter-Glo method. Healthy residents living in moderate altitudes have significantly higher levels of cytosolic ATP in their blood (p+≤+0.05) than residents living in low mountains. MAFLD is characterized by an increase in the level of ATP concentration in their blood. ATP concentration decreased significantly in patients with MAFLD with DM2 living in moderate-altitude in comparison to those living in low-altitude mountains. The results suggest that chronic altitude hypoxia leads to a breakdown in adaptive mechanisms of energy metabolism of ATP in patients with MAFLD with type 2 DM.

Exosomes from porcine serum as endogenous additive maintain function of boar sperm during liquid preservation at 17 °C in vitro

The supplementation of sperm culture media with serum is quite common, and improves both sperm survival and motility. However, the link between serum and sperm remains poorly understood. The present study is the first investigation of the effects on sperm quality and function of endogenous porcine serum exosomes in medium used for culturing boar sperm. Scanning electron microscopy (SEM) confirmed that serum-derived exosomes from both castrated boars (cbsExos) and sows (ssExos) exhibited typical nanostructural morphology and expressed CD63, CD9, and Alix, as shown by Western blotting. At 17 °C, the progressive motility and membrane integrity of sperm were significantly increased after incubation of fresh boar semen for 7 days with cbsExos-4 (8 × 1010 particles/mL) or ssExos-16 (32 × 1010 particles/mL). Moreover, cbsExos-4 and ssExos-16 were found to be effective sperm additives, improving mitochondrial transmembrane potential (ΔΨm) and adenosine triphosphate (ATP) content, total antioxidant activity (T-AOC), superoxide dismutase (SOD) activity, and glutathione peroxidase (GPx) activity while reducing reactive oxygen species (ROS) levels, and malondialdehyde (MDA) content following preservation at 17 °C after a 5-day incubation. Both fluorescence and SEM showed that the serum exosomes bound directly to the sperm membrane, suggesting an interaction that could influence sperm-zona pellucida binding. Overall, this study provides new insights into the potential benefits of adding cbsExos and ssExos to enhance the quality of boar sperm during ambient temperature preservation, which may lead to advancements in sperm preservation strategies.

Cultivar-dependent grape berry dehydration in later ripening phases may be associated with energy regulation and ionic homeostasis

Climate warming and drought may alter the progression of sugar accumulation by the grape berry, and contribute to pre-harvest berry shrivel and cell vitality loss which were hypothesised to be associated with solute accumulation cessation and energy status in the berries. To explore the relationship between energy and cultivar-dependent berry cell death, we characterised the variations of pericarp constituents and energy status across five time points, five ripening phases, and three cultivars with various levels of berry shrivel and cell death. Grape berries of Shiraz, Chardonnay and Flame Seedless at the Eichorn-Lorenz stages 33 to 39 were sampled at 5:00, 9:00, 13:00, 17:00 and 21:00 on each sampling day, which were used in the analysis of water percentage, adenosine triphosphate (ATP), ethanol, sugar, L-malic acid, as well as elements with vascular mobility, including potassium (K) and sodium (Na). Shiraz and Chardonnay ceased accumulating sugar and phloem mobile elements during the later ripening phase, while Flame Seedless did not undergo water loss or cease to accumulate solutes in pericarps. Shiraz berry ripening was distinguished by greater pericarp water loss, ATP reduction, increased ion disorder susceptibility as indicated by a lower K/Na ratio, and higher ethanol concentration in the later ripening phase. The Chardonnay pericarp contained the highest ATP concentration and K/Na ratio among the three cultivars. The Flame Seedless pericarp maintained a low but stable K/Na ratio throughout berry ripening. Berry ripening phase impacted the diurnal variations of pericarp water percentage and ATP concentration. The results indicated that energy regulation and ionic homeostasis may be associated with cultivar-dependent grape pericarp hydration, solute accumulation and cell vitality during berry ripening.

Exploring the Role of Surface and Mitochondrial ATP-Sensitive Potassium Channels in Cancer: From Cellular Functions to Therapeutic Potentials.

ATP-sensitive potassium (KATP) channels are found in plasma membranes and mitochondria. These channels are a type of ion channel that is regulated by the intracellular concentration of adenosine triphosphate (ATP) and other nucleotides. In cell membranes, they play a crucial role in linking metabolic activity to electrical activity, especially in tissues like the heart and pancreas. In mitochondria, KATP channels are involved in protecting cells against ischemic damage and regulating mitochondrial function. This review delves into the role of KATP channels in cancer biology, underscoring their critical function. Notably responsive to changes in cellular metabolism, KATP channels link metabolic states to electrical activity, a feature that becomes particularly significant in cancer cells. These cells, characterized by uncontrolled growth, necessitate unique metabolic and signaling pathways, differing fundamentally from normal cells. Our review explores the intricate roles of KATP channels in influencing the metabolic and ionic balance within cancerous cells, detailing their structural and operational mechanisms. We highlight the channels' impact on cancer cell survival, proliferation, and the potential of KATP channels as therapeutic targets in oncology. This includes the challenges in targeting these channels due to their widespread presence in various tissues and the need for personalized treatment strategies. By integrating molecular biology, physiology, and pharmacology perspectives, the review aims to enhance the understanding of cancer as a complex metabolic disease and to open new research and treatment avenues by focusing on KATP channels. This comprehensive approach provides valuable insights into the potential of KATP channels in developing innovative cancer treatments.

TFR1 knockdown alleviates iron overload and mitochondrial dysfunction during neural differentiation of Alzheimer’s disease-derived induced pluripotent stem cells by interacting with GSK3B

Iron metabolism disorders are implicated in the pathogenesis of Alzheimer’s disease (AD). It was previously reported that transferrin receptor (TFR1) expression was upregulated in AD mouse model. However, the precise biological functions of TFR1 in AD progression remains unclear. Herein, we observed a gradual increase in TFR1 protein expression during the differentiation of AD patient-derived induced pluripotent stem cells (AD-iPS). TFR1 knockdown inhibited the protein expression of ferritin and ferritin heavy chain 1 (FTH1), enhanced the expression of ferroportin 1 (FPN1), and decreased intracellular levels of total iron, labile iron, and reactive oxygen species (ROS). Moreover, TFR1 knockdown improved mitochondrial membrane potential (MMP), increased adenosine triphosphate (ATP) content, downregulated mitochondrial fission proteins, and upregulated mitochondrial fusion proteins. TFR1 knockdown alleviated iron overload and mitochondrial dysfunction in neural cells differentiated from AD-iPS, while TFR1 overexpression showed the opposite results. Additionally, TFR1interacted with glycogen synthase kinase 3 beta (GSK3B) and promoted GSK3B expression. GSK3B overexpression reversed the inhibitory effects of TFR1 knockdown on iron overload and mitochondrial dysfunction in AD-iPS differentiated neural cells. In conclusion, TFR1 knockdown alleviated iron overload and mitochondrial dysfunction in neural cells differentiated from AD-iPS by promoting GSK3B expression. Our findings provide a potential therapeutic target for the treatment of AD.Graphical

Effect of Erchen Decoction on liver mitochondrial function by inhibiting mTORC1/SREBP1/CAV1 pathway in mice with high-fat diet

This study aims to investigate the effect of Erchen Decoction(ECD) on liver mitochondrial function in mice with a high-fat diet and its possible mechanism. A total of sixty C57BL/6J mice were randomly divided into a normal group, high-fat group, ECD group, mTORC1 activator(MHY) group, ECD+MHY group, and polyene phosphatidyl choline(PPC) group, with 10 rats in each group. The normal group was given a normal diet, and the other groups were fed a high-fat diet for 20 weeks. At the 17th week, the ECD group and ECD+MHY group were given ECD(8.7 g·kg~(-1)) daily, and the PPC group was given PPC(0.18 g·kg~(-1)) daily, while the remaining groups were given normal saline(0.01 mL·g~(-1)) daily for four weeks. In the 19th week, the MHY group and ECD+MHY group were injected intraperitoneally with MHY(5 mg·kg~(-1)) every other day for two weeks. During the experiment, the general conditions of the mice were observed. The contents of triglyceride(TG) and total cholesterol(TC) in serum were measured. Morphological changes in liver tissue were examined through HE and oil red O staining. The content of adenosine triphosphate(ATP) was determined using chemiluminescence, and mitochondrial membrane potential was assessed using a fluorescence probe(JC-1). Western blot was performed to detect the expression of rapamycin target protein complex 1(mTOR1), ribosomal protein S6 kinase B1(S6K), sterol regulatory element binding protein 1(SREBP1), and caveolin 1(CAV1). RESULTS:: revealed that compared with the normal group, the mice in the high-fat group exhibited significant increases in body weight and abdominal circumference(P<0.01). Additionally, there were significant increases in TG and TC levels(P<0.01). HE and oil red O staining showed that the boundaries of hepatic lobules were unclear; hepatocytes were enlarged, round, and irregularly arranged, with obvious lipid droplet deposition and inflammatory cell infiltration. The liver ATP content and mitochondrial membrane potential decreased significantly(P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 increased significantly(P<0.01), while the expression of CAV1 decreased significantly(P<0.01). Compared with the high-fat group, the body weight and TG content of mice in the ECD group and PPC group decreased significantly(P<0.05). Improvements were observed in hepatocyte morphology, lipid deposition, and inflammatory cell infiltration. Furthermore, there were significant increases in ATP content and mitochondrial membrane potential(P<0.05 or P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly in the ECD group(P<0.01), while CAV1 expression increased significantly(P<0.01). However, the indices mentioned above did not show improvement in the MHY group. When the ECD+MHY group was compared with the MHY group, there were significant reductions in body weight and TG contents(P<0.05). The morphological changes of hepatocytes, lipid deposition, and inflammatory cell infiltration were recovered. Moreover, there were significant increases in liver ATP content and mitochondrial membrane potential(P<0.05 or P<0.05). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly(P<0.01), while CAV1 expression increased significantly(P<0.01). In conclusion, ECD can improve mitochondrial function by regulating the mTORC1/SREBP1/CAV1 pathway. This mechanism may be involved in the resolution of phlegm syndrome and the regulation of lipid metabolism.

Correction of mitochondrial dysfunction with trimethoxy-substituted monocarbonyl curcumin analogues in experimental Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disease that is a terminal form of dementia with an alarming spread rate. The treatment of AD usually involves symptomatic therapy, but the research field for new medicines to correct AD focus on the pathogenetic keys of the disease, i.e., a mitochondrial dysfunction.The aim of the work was to evaluate the effect of trimethoxy-substituted monocarbonyl curcumin analogues on changes in the mitochondrial function of the hippocampus in AD rats.Materials and methods. AD was modeled in female Wistar rats by the injection of β-amyloid aggregates 1-42 into the CA1 part of the hippocampus. The tested compounds AZBAX4 and AZBAX6 at a dose of 20 mg/kg each, as well as the reference donepezil at a dose of 50 mg/kg, were administered orally for 30 days after the surgery. After the specified time had passed, the changes in the cellular respiration, a citrate synthase activity, cytochrome-c-oxidase, succinate dehydrogenase, and adenosine triphosphate (ATP) concentrations were evaluated in the mitochondrial fraction of the rat hippocampus.Results. During the study, it was shown that the use of AZBAX4 and AZBAX6 compounds contributed to an increase in the intensity of aerobic metabolism by 83.9 (p <0.05) and 35.9% (p <0.05), respectively, while reducing the activity of anaerobic one by 27.7 (p <0.05) and 20.6% (p <0.05), respectively. Against the background of the tested compounds AZBAX4 and AZBAX6 administration, there was also a significant increase in the activity of citrate synthase, succinate dehydrogenase and cytochrome-c-oxidase, as well as the level of ATP in the hippocampal tissue by 112.8 (p <0.05) and 117.1% (p <0.05), respectively. The use of donepezil led to a significant increase in the intensity of aerobic reactions – by 24.0% (p <0.05), a citrate synthase activity– by 80.0% (p <0.05) and the ATP concentration – by 68.5% (p <0.05). Against the background of the use of the analyzed substances, a decrease in the apoptosis-inducing factor and mitochondrial hydrogen peroxide is also worth noting.Conclusion. Based on the obtained data, it can be assumed that the use of AZBAX4 and AZBAX6 compounds contributes to an increase in the functional activity of the mitochondria of hippocampal cells of AD rats, while surpassing the reference donepezil. It is perspective to continue a further study of AZBAX4 and AZBAX6 compounds as possible medicines of a pathogenetic correction of AD.

NH2-MIL-101(Fe)-mediated photo-Fenton reaction enhanced simultaneous removal of nitrogen and refractory organics in anammox process through interfacial electron transfer

In this study, H2O2 (0.1 ‰) and NH2-MIL-101(Fe)-driven (150 mg/L) photo-Fenton-coupled anammox were proposed to simultaneously improve the removal efficiency of nitrogen and humic acid. Long-term experiments showed that the total nitrogen removal efficiency was increased by the photo-Fenton reaction to 91.9 ± 1.5 % by altering the bioavailability of refractory organics. Correspondingly, the total organic carbon removal efficiency was significantly increased. Microbial community analyses indicated that Candidatus_Brocadia maintained high activity during photo-Fenton reaction and was the most abundant genus in the reactor. Dissimilatory nitrate reduction to ammonium process and denitrification process were enhanced, resulting in reduced NO3–-N production. The establishment of electron transfer between microorganisms and NH2-MIL-101 (Fe) improved the charge separation efficiency of the quantum dots and increased the intracellular adenosine triphosphate content of anammox bacteria. These results indicated that photo-Fenton-anammox process promoted the removal of nitrogen and refractory organics in one reactor which had good economic value and application prospects.

Mitochonic Acid 5 Increases Ram Sperm Quality by Improving Mitochondrial Function during Storage at 4 °C

Semen preservation involves lengthening sperm’s fertile lifespan without any detrimental effects on its biochemical, functional, and ultrastructural properties. Liquid storage at 4 °C is a ram sperm preservation method. However, this method of storage causes irreversible damage due to cold shocks, osmotic stresses, oxidative stresses, and reductions in sperm metabolism. The present study aims to investigate whether the supplementation of mitochonic acid 5 (MA-5) in a sperm extender could improve chilled ram sperm quality and elucidate its mechanism of action. Ram sperm were diluted with a tris-citrate-glucose extender containing different concentrations of MA-5 (0, 0.1, 1, 10, and 100 nM) and stored at 4 °C for up to 48 h. Sperm motility, membrane integrity, acrosome integrity, mitochondrial membrane potential, reactive oxygen species (ROS) level, ATP content, and the expression of NADPH dehydrogenase subunits 1 (MT-ND1) and NADPH dehydrogenase subunits 6 (MT-ND6) were evaluated. It was observed that compared to the control, the 10 nM MA-5 treatment significantly (p < 0.05) increased total motility (82 ± 3.5% vs. 76 ± 5.9%), progressive motility (67.6 ± 8.2% vs. 51 ± 8.3%), and other parameters (straight-line velocity (VSL), average path velocity (VAP), and curvilinear velocity (VCL)). In addition, 10 nM MA-5 supplementation also improved ram sperm membrane integrity and acrosomal integrity as well increased mitochondrial membrane potential (51.1 ± 0.7% vs. 37.7 ± 1.3%), reduced ROS levels, and elevated adenosine triphosphate (ATP) contents. Furthermore, a Western blot analysis demonstrated that the addition of MA-5 significantly (p < 0.05) increased the expression of MT-ND1 and MT-ND6 proteins in ram sperm, with the 10 nM MA-5 treatment resulting in the highest expression level. These results suggest that MA-5 improves ram sperm quality by maintaining high sperm mitochondrial function during liquid storage at 4 °C.

Rosa roxburghii Tratt Pomace Crude Extract Inactivates Cronobacter sakazakii Isolated from Powdered Infant Formula.

Cronobacter sakazakii is an important foodborne pathogen in powder infant formula (PIF). The objective of this study was to evaluate the inactivation effect of Rosa roxburghii Tratt pomace crude extract (RRPCE) on C. sakazakii isolated from PIF and to reveal the mechanism of action. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were used to evaluate the inhibitory activity of RRPCE against C. sakazakii. The inhibitory mechanism was revealed from the perspective of effects of RRPCE on intracellular adenosine 5'-triphosphate (ATP), reactive oxygen species (ROS), membrane potential, protein and nucleic acid leakage, and cell morphology of C. sakazakii. The inactivation effects of RRPCE on C. sakazakii in biofilms on stainless steel, tinplate, glass, silica gel, polyethylene terephthalate, and polystyrene to evaluate its potential as a natural disinfectant. The results showed that the MIC and MBC of RRPCE against C. sakazakii were 7.5 and 15 mg/mL, respectively. After treatments with RRPCE, intracellular ATP content decreased significantly while intracellular ROS level increased significantly (p < 0.05). The cell membrane depolarization, large leakage of proteins and nucleic acids, and severely damaged cell morphology also occurred in C. sakazakii treated with RRPCE. In addition, a 20-minute treatment with 2 MIC (15 mg/mL) of RRPCE could inactivate all C. sakazakii (from 6.10 to 6.40 CFU/mL) in biofilms on all six contact surfaces. Our findings suggest that RRPCE is ideal for the inactivation of C. sakazakii and has the potential to be used as a natural disinfectant for the inactivation of PIF packaging materials and containers.

Thioredoxin-2 suppresses hydrogen peroxide–activated nuclear factor kappa B signaling via alleviating oxidative stress in bovine adipocytes

During the periparturient period, both oxidative stress, and inflammation of adipose tissue are considered high risk factors for metabolic disorder of dairy cows. Oxidative stress can activate transcription factor nuclear factor kappa B (NF-κB), which lead to the upregulation of genes involved in inflammatory pathways. Thioredoxin-2 (TXN2) is a mitochondrial protein that regulates cellular redox by suppressing mitochondrial reactive oxygen species (ROS) generation in nonruminant, whereas the function of TXN2 in bovine adipocytes was unclear. Thus, the objective of this study was to evaluate how or by which mechanisms TXN2 regulates oxidative stress and NF-κB signaling pathway in bovine adipocytes. Bovine pre-adipocytes isolated from 5 healthy Holstein cows were differentiated and used for (1) treatment with different concentrations of hydrogen peroxide (H2O2; 0, 25, 50, 100, 200, or 400 μM) for 2 h; (2) transfection with or without TXN2 small interfering RNA (si-TXN2) for 48 h and then treated with or without 200 μM H2O2 for 2 h; (3) transfection with scrambled negative control siRNA (si-control) or si-TXN2 for 48 h, and then treatment with or without 10 mM N-acetylcysteine (NAC) for 2 h; (4) transfection with or without TXN2-overexpressing plasmid for 48 h and then treatment with or without 200 μM H2O2 for 2 h. High concentrations of H2O2 (200 and 400 μM) decreased protein and mRNA abundance of TXN2, reduced total antioxidant capacity (T-AOC) and ATP content in adipocytes. Moreover, 200 and 400 μM H2O2 reduced protein abundance of inhibitor of kappa B α (IκBα), increased phosphorylation of NF-κB and upregulated mRNA abundance of tumor necrosis factor-α (TNFA) and interleukin-1B (IL-1B), suggesting that H2O2-induced oxidative stress and activated NF-κB signaling pathway. Silencing of TXN2 increased intracellular ROS content, phosphorylation of NF-κB and mRNA abundance of TNFA and IL-1B, decreased ATP content and protein abundance of IκBα in bovine adipocytes. Knockdown of TXN2 aggravated H2O2-induced oxidative stress and inflammation. In addition, treatment with antioxidant NAC ameliorated oxidative stress and inhibited NF-κB signaling pathway in adipocytes transfected with si-TXN2. In bovine adipocytes treated with H2O2, overexpression of TXN2 reduced the content of ROS and elevated the content of ATP and T-AOC. Overexpression of TXN2 alleviated H2O2-induced inflammatory response in adipocytes, as demonstrated by decreased expression of phosphorylated NF-κB, TNFA, IL-1B, as well as increased expression of IκBα. Furthermore, the protein and mRNA abundance of TXN2 was lower in adipose tissue of dairy cows with clinical ketosis. Overall, our studies contribute to the understanding of the role of TXN2 in adipocyte oxidative stress and inflammatory response.