Energy Metabolism Disorder Research Articles

Potential Applications of Thyroid Hormone Derivatives in Obesity and Type 2 Diabetes: Focus on 3,5-Diiodothyronine (3,5-T2) in Psammomys obesus (Fat Sand Rat) Model.

3,5-Diiodothyronine (3,5-T2) has been shown to exert pleiotropic beneficial effects. In this study we investigated whether 3,5-T2 prevent several energy metabolism disorders related to type 2 diabetes mellitus (T2DM) in gerbils diabetes-prone P. obesus. 157 male gerbils were randomly to Natural Diet (ND-controlled) or a HED (High-Energy Diet) divided in: HED- controlled, HED-3,5-T2 and HED- Placebo groups. 3,5-T2 has been tested at 25 µg dose and was administered under subcutaneous pellet implant during 10 weeks. Isolated hepatocytes were shortly incubated with 3,5-T2 at 10−6 M and 10−9 M dose in the presence energetic substrates. 3,5-T2 treatment reduce visceral adipose tissue, prevent the insulin resistance, attenuated hyperglycemia, dyslipidemia, and reversed liver steatosis in diabetes P. obesus. 3,5-T2 decreased gluconeogenesis, increased ketogenesis and enhanced respiration capacity. 3,5-T2 potentiates redox and phosphate potential both in cytosol and mitochondrial compartment. The use of 3,5-T2 as a natural therapeutic means to regulate cellular energy metabolism. We suggest that 3,5-T2 may help improve the deleterious course of obesity and T2DM, but cannot replace medical treatment.

Systematic impacts of fluoride exposure on the metabolomics of rats

Fluoride is widely present in the environment. Excessive fluoride exposure leads to fluorosis, which has become a global public health problem and will cause damage to various organs and tissues. Only a few studies focus on serum metabolomics, and there is still a lack of systematic metabolomics associated with fluorosis within the main organs. Therefore, in the current study, a non-targeted metabolomics method using gas chromatography-mass spectrometry (GC-MS) was used to research the effects of fluoride exposure on metabolites in different organs, to uncover potential biomarkers and study whether the affected metabolic pathways are related to the mechanism of fluorosis. Male Sprague-Dawley rats were randomly divided into two groups: a control group and a fluoride exposure group. GC-MS technology was used to identify metabolites. Multivariate statistical analysis identified 16, 24, 20, 20, 24, 13, 7, and 13 differential metabolites in the serum, liver, kidney, heart, hippocampus, cortex, kidney fat, and brown fat, respectively, in the two groups of rats. Fifteen metabolic pathways were affected, involving toxic mechanisms such as oxidative stress, mitochondrial damage, inflammation, and fatty acid, amino acid and energy metabolism disorders. This study provides a new perspective on the understanding of the mechanism of toxicity associated with sodium fluoride, contributing to the prevention and treatment of fluorosis.

The Metabolomic Characterization of Different Types of Coronary Atherosclerotic Heart Disease in Male.

Background In clinical practice, many patients with coronary atherosclerotic heart disease (CAD) have atypical clinical symptoms. It is difficult to accurately identify stable CAD or unstable CAD early through clinical symptoms and coronary angiography. This study aimed to screen the potential metabolite biomarkers in male patients with stable CAD and unstable CAD. Methods In this work, the metabolomic characterization of the male patients with healthy control (n = 42), stable coronary artery disease (n = 60), non-ST-elevation acute coronary syndrome (n = 45), including prepercutaneous corona intervention (n = 14), and postpercutaneous coronary intervention (n = 31) were performed by using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The serum samples of patients were analyzed by multivariate statistics. Results Results showed that 17 altered metabolites were identified to have a clear distinction between the stable CAD group and the healthy subjects. Compared with the stable coronary artery disease group, 15 specific metabolite markers were found in the acute coronary syndrome group. The percutaneous coronary intervention also affected the metabolic behavior of patients with CAD. Conclusions In summary, CAD is closely related to energy metabolism, lipid metabolism, and amino acid metabolism disorders. The different metabolic pattern characteristics of healthy, stable coronary artery disease and acute coronary syndrome are constructed, which brings a novel theoretical basis for the early diagnosis of patients with stable and unstable CAD.

Super-Resolution Quantification of T2DM-Induced Mitochondrial Morphology Changes and Their Implications in Pharmacodynamics of Metformin and Sorafenib.

Mitochondria, as the powerhouse of cells, are involved in various processes of cellular homeostasis, especially energy metabolism. The morphology of mitochondria is a critical indicator for their functions, referring to mitochondrial fusion and fission. Here, we performed structured illumination microscopy (SIM) to measure the mitochondrial morphology in living cells. Benefitting from its nano-scale resolution, this SIM-based strategy can quantify the fusion and fission of mitochondria with high sensitivity. Furthermore, as type 2 diabetes mellitus (T2DM) is caused by a disorder of energy substrate utilization, this strategy has the potential to study T2DM by analyzing the mitochondrial morphology of insulin-resistant (IR) cells. With SIM, we found that mitochondrial fission was increased in IR MRC-5, LO2, FHs 74 Int, and HepG2 cells but not in IR Huh7 cells with high-invasiveness ability. Furthermore, we found that metformin could inhibit mitochondrial fission in IR cells, and sorafenib could promote mitochondrial fusion in HepG2 cancer cells, especially in those IR cells. To conclude, mitochondrial fission is involved in T2DM, and cancer cells with high-invasiveness ability may be equipped with stronger resistance to energy metabolism disorder. In addition, the pharmacodynamics of metformin and sorafenib in cancer may be related to the inhibition of mitochondrial fission, especially for patients with T2DM.

Molluscicidal activity of the secondary metabolites from Streptomyces nigrogriseolus XD 2-7 against Oncomelania hupensis and its preliminary mechanisms of molluscicidal actions

To evaluate the storage stability of metabolites from actinomycetes Streptomyces nigrogriseolus XD 2-7 and the mollcuscicidal activity against Oncomelania hupensis in the laboratory, and to preliminarily explore the mechanisms of the molluscicidal activity. The fermentation supernatant of S. nigrogriseolus XD 2-7 was prepared and stored at -20, 4 °C and 28 °C without light for 10 d; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation supernatant was boiled in a 100 °C water bath for 30 min and recovered to room temperature, and then the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The pH values of the fermentation supernatant were adjusted to 4.0, 6.0 and 9.0 with concentrated hydrochloric acid and sodium hydroxide, and the fermentation supernatant was stilled at room temperature for 12 h, with its pH adjusted to 7.0; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation product of S. nigrogriseolus XD 2-7was isolated and purified four times with macroporous resin, silica gel and octadecylsilane bonded silica gel. The final products were prepared into solutions at concentrations of 10.00, 5.00, 2.50, 1.25 mg/L and 0.63 mg/L, and the molluscicidal effect of the final productswas tested against O. hupensis following immersion for 72 h, while dechlorination water served as blank controls, and 0.10 mg/L niclosamide served as positive control. The adenosine triphosphate (ATP) and adenosine diphosphate (ADP) levels were measured in in O. hupensis soft tissues using high performance liquid chromatography (HPLC) following exposure to the final purified fermentation products of S. nigrogriseolus XD 2-7. After the fermentation supernatant of S. nigrogriseolus XD 2-7 was placed at -20, 4 °C and 28 °C without light for 10 d, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100% (30/30) O. hupensis mortality. Following boiling at 100 °C for 30 min, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100.00% (30/30) O. hupensis mortality. Following storage at pH values of 4.0 and 6.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 100.00% (30/30) O. hupensis mortality, and following storage at a pH value of 9.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 33.33% (10/30) O. hupensis mortality (χ2 = 30.000, P < 0.05). The minimum concentration of the final purified fermentation products of S. nigrogriseolus XD 2-7 was 1.25 mg/L for achieving a 100% (30/30) O. hupensis mortality. The ATP level was significantly lower in O. hupensis soft tissues exposed to 0.10 mg/L and 1.00 mg/L of the final purified fermentation products of S. nigrogriseolus XD 2-7 than in controls (F = 7.274, P < 0.05), while no significant difference was detected in the ADP level between the treatment group and controls (F = 2.485, P > 0.05). The active mollcuscicidal ingredients of the S. nigrogriseolus XD 2-7 metabolites are maintained stably at -20, 4 °C and 28 °C for 10 d, and are heat and acid resistant but not alkali resistant. The metabolites from S. nigrogriseolus XD 2-7 may cause energy metabolism disorders in O. hupensis, leading to O. hupensis death.

Effect of Dihydroquercetin on Energy Metabolism in LPS-Induced Inflammatory Mice.

This study investigated the effects and alterations of dihydroquercetin on the growth performance, nutriment metabolism, antioxidant and immune function, and energy substrate utilization in lipopolysaccharide-challenged mice. A total of 0, 50, and 200 mg/kg of dihydroquercetin were intragastrically administered once a day for 21 days. After the pretreatment with dihydroquercetin, each group was subjected to a lipopolysaccharide challenge (except for the control group). After lipopolysaccharide injection, food intake, body weight, metabolic indexes of blood and liver nutrients, blood inflammatory factors, and liver oxidative stress indexes were measured at 6, 12, 24, and 48 h, respectively. Indirect calorimetry analysis was performed by respiratory gas analysis for 48 h to calculate the energy substrate metabolism of carbohydrate, fat, and protein. Urinary nitrogen excretion was measured to evaluate the urinary protein metabolism to calculate the substrate utilization. The results showed that dihydroquercetin pretreatment can significantly increase the weight gain and average food intake and decrease the mortality rate in lipopolysaccharide-induced inflammation mice. Furthermore, dihydroquercetin pretreatment can alleviate the negative effects of lipopolysaccharides by increasing levels of superoxide dismutase and glutathione peroxidase and by decreasing the malondialdehyde and serum inflammatory cytokines (interleukin-1β, nuclear factor κB, and interleukin-6). Dihydroquercetin pretreatment also can relieve nutrient metabolic disorder by increasing blood glucose, serum total protein, and liver glycogen levels and reducing serum and liver triglycerides, serum cholesterol, serum lactate dehydrogenase, and serum urea nitrogen levels. Meanwhile, it increases the relative utilization of carbohydrate, reducing relative utilization of protein and lipid, alleviating the change in energy metabolism pattern from glucose-predominant to lipid-predominant caused by lipopolysaccharide stimulation. In addition, the degree of metabolic pattern transformation depends on the dose of dihydroquercetin supplement. Finally, according to principal component analysis, we found that the inflammation was strongest in the mice at 24 h and was subsequently relieved in the LPS-stimulated group, whereas in the dihydroquercetin-pretreated group, the inflammation was initially relieved. To summarize, dihydroquercetin pretreatment can improve energy metabolism disorder and attenuate the negative effects of lipopolysaccharide challenge in mice from the initial stage of inflammation.

Effect of Rehmanniae Radix Praeparata on energy metabolism in prefrontal cortex of rats with attention deficit hyperactivity disorder based on "static Yin and dynamic Yang" theory

The present study investigated the effect of Rehmanniae Radix Praeparata(RRP) on the energy metabolism of prefrontal cortex(PFC) of spontaneously hypertensive rats with attention deficit hyperactivity disorder(ADHD) based on the &quot;static Yin and dynamic Yang&quot; theory.Thirty spontaneously hypertensive male rats aged 3 weeks were randomly divided into a model group, a methylphenidate(MPH) group(2 mg·kg~(-1)), and an RRP group(2.4 g·kg~(-1)).Wistar-Kyoto(WKY) male rats of the same age were assigned to the normal group.Rats were treated with corresponding drugs twice per day, and those in the model group and the normal group received the same volume of 0.9% sodium carboxymethyl cellulose(CMC-Na) solution by gavage.The open-field test was performed to evaluate the spontaneous and impulsive behaviors of rats before treatment and on the 4~(th) week after treatment.Four weeks after treatment, PFC was isolated and mitochondria were prepared.The content of adenosine triphosphate(ATP), adenosine diphosphate(ADP), and adenosine monophosphate(AMP) in the PFC was determined by high-performance liquid chromatography(HPLC), and energy charge(EC) was calculated.The parameters related to mitochondrial respiratory function were measured by the Clark oxygen electrode, specifically, state 3 respiration(ST3), state 4 respiration(ST4), and respiratory control rate(RCR).Enzymatic activities of succinate dehydrogenase(SDH), cytochrome C oxidase(COX), Na~+-K~+-ATPase, and Ca~(2+)-Mg~(2+)-ATPase were measured by chemical colorimetry.Mitochondrial permeability transition pore(mPTP) opening was measured by spectrophotometry.Protein expression of glucose transporter 1(GLUT1) and GLUT3 in PFC was tested by Western blot.Compared with the results in the model group, RRP could significantly reduce the total distance of movement, vertical times, and distance in the central area in the open field test(P&lt;0.05 or P&lt;0.01), increase the content of ATP and EC, decrease the content of AMP(P&lt;0.05), elevate ST3 and RCR(P&lt;0.05), potentiate activities of SDH, COX, Na~+-K~+-ATPase, and Ca~(2+)-Mg~(2+)-ATPase(P&lt;0.05 or P&lt;0.01), inhibit the opening of mPTP, and increase the expression levels of GLUT1 and GLUT3 proteins(P&lt;0.05).It was inferred that RRP could inhibit hyperacti-vity and impulsivity by improving the energy metabolism disorder in PFC of ADHD rats, and its mechanism may be related to the improvement of mitochondrial respiratory function, potentiation of Na~+-K~+-ATPase, Ca~(2+)-Mg~(2+)-ATPase, and mitochondrial respiratory enzymes, inhibition of the opening of mPTP, and up-regulation of the expression of glucose transporter proteins.This study initially reveals the biological connotation of the &quot;static Yin and dynamic Yang&quot; theory in ADHD.

Dietary adenosine 5'-monophosphate supplementation increases food intake and remodels energy expenditure in mice.

BackgroundDietary nucleotides [inclusion adenosine 5’-monophosphate (AMP)] supplementation was shown to promote the feed intake of sows and increase the AMP content in their milk in our previous work, but whether AMP shapes the energy expenditure and lipid metabolism in mammals remains unknown. Here, we aimed to explore the effects and the related mechanism of dietary AMP supplementation on food intake, body composition, energy expenditure, and lipid metabolism in male mice.Methods4-week-old C57BL/6 mice (After a 1-wk adaptation) were fed with basal diet and basal diet supplemented with 0.1% AMP, respectively. Animal food intake and body weight were monitored and after 4 weeks all animals were sacrificed to measure the body composition, energy expenditure and lipid metabolism changes.ResultsCompared with the control, the 0.1% AMP fed mice showed higher food intake while lower adipose weight. Intriguingly, dietary AMP supplementation was found to stimulate brown adipose tissue thermogenesis as evidenced by the increase in the uncoupling protein-1 level and the core temperature. Moreover, AMP supplementation was shown to promote white adipose tissue lipolysis as indicated by smaller lipid droplet size in mice. These results demonstrate that dietary AMP supplementation could enhance oxygen consumption and energy expenditure.ConclusionsThis study highlights the physiological importance of AMP supplementation in mediating food intake and energy expenditure and suggests its potential as an adjuvant therapy in preventing energy metabolic disorders (mainly obesity and diabetes).

Study on the pharmacodynamic effect of Rhizoma Dioscoreae polysaccharides on cerebral ischemia-reperfusion injury in rats and the possible mechanism

Ethnopharmacological relevanceRhizoma Dioscoreae (RD) is the rhizome of Dioscorea opposita Thunb., a traditional Chinese medicine, which can treat hypertension, diabetes, cerebral vasospasm headache and Alzheimer's disease. Meanwhile, RD is the main component of Liuwei Dihuang pill, a Chinese patent medicine. Rhizoma Dioscoreae polysaccharides (RDPS) are the primary active ingredient of RD. Modern medical research confirmed RDPS has multiple pharmacological effects, including neuroprotection, immunoregulation, antioxidant effect in many organs. The primary ischemia/hypoxia injury and secondary reperfusion injury are mainly caused by oxidative stress, which caused by hypoxia, such as free radical generation, energy metabolism disorder, intracellular calcium overload, excitatory amino acid release and inflammatory reaction. Aim of the studyWe have investigated the pharmacodynamic effect of RDPS on cerebral ischemia-reperfusion (IR) injury in rats and the possible mechanism in vitro. Materials and methodsThe pharmacodynamic effect of RDPS on IR injury in rats was studied by the construction of the occlusion of middle cerebral artery (MCAO) model, measuring the volume of cerebral infarct area, the content of oxidation index, inflammatory cytokines, and the expression of CaMMKβ in brain tissue. The in vitro study was explored by oxygen-glucose deprivation/glycogen reoxygenation (OGD/R) model, construction of the CaMMKβ interference sequence, measuring the expression of CaMMKβ in BV2 cells before and after inhibition of CaMMKβ, and the influence of RDPS on Nrf2/HO-1 signal pathway, in order to investigate the possible mechanism. ResultsCompared with the model group, the present study showed that RDPS with high-dose and low-dose groups could significantly reduce the volume of cerebral infarction. The content of MDA decreased and the activities of GSH and SOD increased in the two dose groups of RDPS. We confirmed that after RDPS treatment, the levels of IL-6, IL-1 β and TNF-α in brain tissue were lower than those in model group, and the expression of CaMMKβ in brain tissue of rats decreased in the model group, but increased in the groups of RDPS. In the in vitro study, compared with the control group, RDPS could regulate the OGD/R-induced apoptosis of BV2 cells and increase the level of CaMMKβ, Nrf2 and HO-1 induced by OGD/R. To our surprise, these therapeutic effects are no longer present after the inhibition of CaMMKβ protein. The activity of BV2 induced by OGD/R could not be enhanced by RDPS after the inhibition of CaMMKβ protein. ConclusionsRDPS has the pharmacodynamic effect in IR injury, which reduce the area of cerebral infarction, up-regulate the activity of anti-oxidant kinase, and down-regulate the inflammatory cytokine. Additionally, RDPS could affect the activation of Nrf2/HO-1 signaling pathway by regulating the expression of CaMMKβ. Our observations justify the RDPS could be a new strategy for IR injury therapy, and the mechanism may be related to the improvement of antioxidant enzyme activity and inhibition of inflammatory reaction.

Protective effect of 5,6,7,8-Tetrahydroxyflavone on high altitude cerebral edema in rats

High altitude cerebral edema (HACE) is a potentially life-threatening disease encountered at high altitudes. However, effective methods for HACE prophylaxis are limited. Convincing evidence confirms that oxidative stress induced by hypobaric hypoxia (HH) is one of the main factors that account for the development of HACE. 5,6,7,8-Tetrahydroxyflavone (THF), a flavone with four consecutive OH groups in ring A, exhibited excellent antioxidant activity in vitro and could attenuate HH induced injury in vivo. The aim of this study was to investigate the protective effect of THF against HACE and its underlying mechanisms. THF administration significantly suppressed HH induced oxidative stress by reducing the formation of hydrogen peroxide and malondialdehyde, by increasing the levels of glutathione and superoxide dismutase in brain tissue. Simultaneously, THF administration inhibited inflammatory responses by decreasing the levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in serum and brain tissue. In addition, THF administration mitigated the energy metabolism disorder induced by HACE as evidenced by decreased levels of lactic acid, lactate dehydrogenase and pyruvate kinase as well as increased ATP levels and ATPase activities. Furthermore, THF administration decreased the expression of matrix metalloproteinase-9, aquaporin 4, hypoxia-inducible factor-1α and vascular endothelial growth factor, which attenuated blood-brain barrier (BBB) disruption and brain edema. Additionally, THF administration improved HACE induced cognitive dysfunction. These results show that THF is a promising agent in the prevention and treatment of HACE.

Energy Metabolic Disorder of Astrocytes May Be an Inducer of Migraine Attack

Migraine is a chronic headache disease, which ranks second in years lost due to disability. However, the mechanism of migraines is still not clear. In migraine patients, fasting can trigger headache attacks. We explored the probable mechanism of why fasting can induce headaches. Nitroglycerin (NTG) was used to induce acute migraine attacks in mice. Primary astrocytes were used to study the pathophysiological mechanism and a Seahorse analyzer was used to detect mitochondrial function. NTG induced more serious headaches in the fasting group. Both the head-scratching times and climbing-cage times in the fasting group were higher than those in normal-diet group. More ROS and inflammatory factors, such as IL-6 and IL-1β, were induced in low-glucose conditions. Seahorse showed that the basal oxygen consumption rate (OCR) and OCR for ATP production were lower in mice who had received NTG with low glucose levels than in other groups. The activity of AMPK was inhibited in this group, which may explain the Seahorse results. We concluded that in the low-glucose state, astrocytes produce more inflammatory factors, ROS, which may be a result of mitochondrial metabolism dysfunction. Improving mitochondrial function and supplying enough substrates may be an option for relieving migraine attacks.

Glycyrrhiza uralensis promote the metabolism of toxic components of Aconitum carmichaeli by CYP3A and alleviate the development of chronic heart failure.

Aconitum, as "the first drug of choice for invigorating Yang and saving lives", has been widely used for the treatment of heart failure. However, toxic components of Aconitum can easily lead to serious arrhythmia, even death (Y. CT., 2009; Zhang XM., 2018). In this study, a High Performance Liquid Chromatography (HPLC) method for the determination of aconitine (AC), mesaconitine (MA) and hypaconitine (HA) was established; The effect of Glycyrrhiza on CYP3A1 / 2 mRNA expression was detected by RT-PCR; SD rats were given Aconitum and compatibility of Glycyrrhizae and Aconitum by gavage respectively, the blood concentration of toxic components were determined by LC-MS / MS; The CHF rat model was established by intraperitoneal injection of adriamycin (2.5 mg / kg), and were randomly divided into model, Aconitum, the compatibility of Glycyrrhizae and Aconitum and Captopril group, 5 mice/group. After 4 weeks of gavage, the corresponding indexes were detected by ELISA and HPLC. The results showed that Ketoconazole significantly inhibited the metabolites of AC, MA and HA; Glycyrrhiza induced CYP3A gene expression; The level of ALD in the compatibility of Glycyrrhizae and Aconitum group was significantly lower than that in Aconitum group. After intervention with the compatibility of Glycyrrhizae and Aconitum, ATP increased, ADP decreased significantly. In conclusion, we found Glycyrrhiza promoted the metabolism of toxic components of Aconitum by up regulating the expression of CYP3A, and reduced the content of BNP, Ang II and ALD, improved the energy metabolism disorder of myocardium, alleviated the development of CHF.

Polystyrene microplastics-induced cardiotoxicity in chickens via the ROS-driven NF-κB-NLRP3-GSDMD and AMPK-PGC-1α axes

Microplastics (MPs) pollution is getting increasingly prominent, and its dangers have attracted widespread attention. The heart is the central hub of the organism's survival, and the mechanism of MPs-induced heart injury in chickens is unknown. Here, we investigated the effects of 5 μm polystyrene microplastics (PS-MPs) on the heart and primary cardiomyocytes of chickens at varied concentrations. We observed that PS-MPs caused severe pathological damage and ultrastructural changes in heart, induced myocardial pyroptosis, inflammatory cell infiltration and mitochondrial lesions. PS-MPs evoked abnormal antioxidant enzyme content and ROS overproduction. Detailed mechanistic investigation indicated that PS-MPs triggered pyroptosis via NF-κB-NLRP3-GSDMD axis and exacerbated myocardial inflammation (NLRP3, Caspase-1, IL-1β, IL-18, ASC, GSDMD, NF-κB, COX-2, iNOS and IL-6 overexpression). Additionally, PS-MPs induced mitochondrial damage (TFAM, OPA1, MFN1 and MFN2 down-expression, DRP1 and Fis1 overexpression) and energy metabolism disorders (HK2, PKM2, PDHX and LDH up-regulation) by inhibiting AMPK-PGC-1α pathway. Interestingly, NAC alleviated these aberrant manifestations in vitro. We suggested that PS-MPs driven alterations in NF-κB-NLRP3-GSDMD and AMPK-PGC-1α pathways via ROS overload, which in turn triggered oxidative stress, myocardial pyroptosis, inflammation, mitochondrial and energy metabolism dysfunction. This provided theoretical bases for protecting chickens from toxic injury by MPs.

Therapeutic Effect of Buyang Huanwu Decoction on the Gut Microbiota and Hippocampal Metabolism in a Rat Model of Cerebral Ischemia.

Buyang Huanwu decoction (BHD) is a well-known Chinese herbal prescription. It has been widely used in the clinical treatment of cerebral ischemia (CI) in China. However, the mechanism underlying the treatment of CI with BHD remains to be elucidated. In this study, we combined microbiomic and metabolomic strategies to explore the therapeutic effects of BHD on middle cerebral artery occlusion (MCAO) in rats. Our results showed that BHD could effectively improve neurological severity scores and alleviate neuronal damage in rats with MCAO. BHD could also reduce the level of peripheral proinflammatory cytokines and inhibit neuroinflammation. 16S rRNA sequencing showed that BHD could increase the relative abundances of the genera Lactobacillus, Faecalibacterium, Ruminococcaceae_UCG-002, etc., while decreasing the relative abundances of the genera Escherichia-Shigella, Klebsiella, Streptococcus, Coprococcus_2, Enterococcus, etc. Untargeted metabolomic analysis of hippocampal samples showed that 17 significantly differentially abundant metabolites and 9 enriched metabolic pathways were linked with BHD treatment. We also found that the regulatory effects of BHD on metabolites were correlated with the differentially abundant microbial taxa. The predicted function of the gut microbiota and the metabolic pathway enrichment results showed that purine metabolism, glutamatergic synapses, arginine and proline metabolism, and alanine, aspartic acid and glutamate metabolism were involved in the effects of BHD. These pathways may be related to pathological processes such as excitotoxicity, neuroinflammation, and energy metabolism disorder in CI. In summary, these findings suggest that regulation of hippocampal metabolism and of the composition and function of the gut microbiota may be important mechanisms underlying the effect of BHD in the treatment of CI.

Metformin alleviates the cognitive impairment caused by aluminum by improving energy metabolism disorders in mice

Long-term exposure to environmental aluminum was found to be related to the occurrence and development of neurodegenerative diseases. Energy metabolism disorders, one of the pathological features of neurodegenerative diseases, may occur in the early stage of the disease and are of potential intervention significance. Here, sub-chronic aluminum exposure mouse model was established, and metformin was used to intervene. We found that sub-chronic aluminum exposure decreased the protein levels of phosphorylation AMPK (p-AMPK), glucose transporter 1 (GLUT1) and GLUT3, taking charge of glucose uptake in the brain, reduced the levels of lactate shuttle-related proteins monocarboxylate transporter 4 (MCT4) and MCT2, as well as lactate content in the cerebral cortex, while increased hypoxia-inducible factor-1α (HIF-1α) level to drive downstream pyruvate dehydrogenase kinase 1 (PDK1) expression, thereby inhibiting pyruvate dehydrogenase (PDH) activity, and ultimately led to ATP depletion, neuronal death, and cognitive dysfunction. However, metformin could rescue these injuries. Thus, it came to a conclusion that aluminum could damage glucose uptake, interfere with astrocyte-neuron lactate shuttle (ANLS), interrupt the balance in energy metabolism, and resulting in cognitive function, while metformin has a neuroprotective effect against the disorder of energy metabolism caused by aluminum in mice.

RNA-Seq and 16S rRNA Analysis Revealed the Effect of Deltamethrin on Channel Catfish in the Early Stage of Acute Exposure.

Deltamethrin (Del) is a widely used pyrethroid insecticide and a dangerous material that has brought serious problems to the healthy breeding of aquatic animals. However, the toxicological mechanisms of Del on channel catfish remain unclear. In the present study, we exposed channel catfish to 0, 0.5, and 5 μg/L Del for 6 h, and analyzed the changes in histopathology, trunk kidney transcriptome, and intestinal microbiota composition. The pathological analyses showed that a high concentration of Del damaged the intestine and trunk kidney of channel catfish in the early stage. The transcriptome analysis detected 32 and 1837 differentially expressed genes (DEGs) in channel catfish trunk kidneys after exposure to 0.5 and 5 μg/L Del, respectively. Moreover, the KEGG pathway and GO enrichment analyses showed that the apoptosis signaling pathway was significantly enriched, and apoptosis-related DEGs, including cathepsin L, p53, Bax, and caspase-3, were also detected. These results suggested that apoptosis occurs in the trunk kidney of channel catfish in the early stage of acute exposure to Del. We also detected some DEGs and signaling pathways related to immunity and drug metabolism, indicating that early exposure to Del can lead to immunotoxicity and metabolic disorder of channel catfish, which increases the risk of pathogenic infections and energy metabolism disorders. Additionally, 16S rRNA gene sequencing showed that the composition of the intestinal microbiome significantly changed in channel catfish treated with Del. At the phylum level, the abundance of Firmicutes, Fusobacteria, and Actinobacteria significantly decreased in the early stage of Del exposure. At the genus level, the abundance of Romboutsia, Lactobacillus, and Cetobacterium decreased after Del exposure. Overall, early exposure to Del can lead to tissue damage, metabolic disorder, immunotoxicity, and apoptosis in channel catfish, and affect the composition of its intestinal microbiota. Herein, we clarified the toxic effects of Del on channel catfish in the early stage of exposure and explored why fish under Del stress are more vulnerable to microbial infections and slow growth.

Ozone preconditioning protects rabbit heart against global ischemia-reperfusion injury in vitro by up-regulating HIF-1α.

Myocardial ischemia-reperfusion injury (MIRI) is a major factor that leads to cardiac dysfunction in cardiovascular surgery during extracorporeal circulation. Recent studies have found that ozone (O3) has protective effect on MIRI caused by the anterior descending branch of the ligated left coronary artery. However, whether O3 preconditioning has the same protective effect on global MIRI and the mechanism underlying this clinical treatment remains elusive. Here, we hypothesized that O3 preconditioning (O3P) could protect rabbit heart against global MIRI in vitro by up-regulating HIF-1α. Rabbits were treated intraperitoneally with O2/O3 mixture with different concentrations and then injected with YC-1 (inhibitor of HIF-1α) before the establishment of the global MIRI model using the Langendorff isolated heart perfusion apparatus. We investigated the effects of O3 preconditioning on cardiac systolic function, myocardial infarction, inflammatory response, mitochondrial function, myocardial pathological changes and arrhythmias. We found that the heart with O3 preconditioning significantly increased HR, LVDP and IL-10 expression, and decreased IL-6 expression, CK-MB, cTnT and cTnI concentration, myocardial infarction area, myocardial pathological injury and the occurrence of ventricular tachycardia and ventricular fibrillation. Meanwhile, the level of HIF-1α was significantly increased. However, after treatment of specific inhibitor of HIF-1α, the protective effect of O3 preconditioning was reversed completely. Our data indicates that O3 preconditioning has protective effect on MIRI and this protective effect is positively associated with dosage of O3. Energy metabolism disorder is the initial stage of MIRI and up-regulation of HIF-1α plays an important role in reducing mitochondrial dysfunction.

Phosphorus metabolism disorders in erythrocytes and lymphocytes among patients with inflammatory breast cancer, infiltrative stomach and colorectal cancer.

Energy and plastic potential dysfunction of erythrocytes and lymphocytes among people with inflammatory breast cancer, infiltrative stomach cancer, and infiltrative colon cancer is characterized by a more aggressive clinical course and poor prognosis. We explored the features of energy metabolism and phosphorus metabolism disorders in the erythrocytes and lymphocytes of patients with inflammatory breast cancer, infiltrative stomach cancer, and infiltrative colon cancer as a predicting factor in the course of the disease. 49 people were examined; the 1st group had infiltrative stomach cancer (n=17); the 2nd group had infiltrative colon cancer (n=11); the 3rd group had inflammatory breast cancer (n=21). Glycerol-3-phosphate dehydrogenase activity was 1.8 times reduced (p≤0.005), and the activity of glyceraldehyde-3-phosphate dehydrogenase in erythrocytes of patients with cancer at the main localization increased 2.5 times, compared with normal. Inflammatory breast cancer patients had a statistically significant decrease (p<0.005) in erythrocytes adenosine triphosphate content by an average of 56.5% compared with the normal ratio, and in cases of patients with gastric and colorectal cancer, a decrease of 67%. Excessive use of phosphorus for energy metabolism and adenosine triphosphate production destroys the balance of energetic and plastic potentials of erythrocytes and lymphocytes in inflammatory breast cancer, infiltrative stomach, and infiltrative colorectal cancers patients.

The Therapeutic Effect and Mechanism of Qishen Yiqi Dripping Pills on Cardiovascular and Cerebrovascular Diseases and Diabetic Complications.

The alterations in vascular homeostasis are deeply involved in the development of numerous diseases, such as coronary heart disease, stroke, and diabetic complications. Changes in blood flow and endothelial permeability caused by vascular dysfunction are the common mechanisms for these three types of diseases. The disorders of glucose and lipid metabolism can bring changes in the energy production patterns in endothelium and surrounding cells which may consequently cause energy metabolic disorders, oxidative stress, and inflammatory responses. Traditional Chinese medicine (TCM) follows the principle of the "treatment by the syndrome differentiation." TCM considers coronary heart disease, stroke, and diabetes complications all as the type of Qi-deficiency and blood stasis syndrome, which mainly occurs in the vascular system. Therefore, the common pathogenesis of these three types of diseases suggests that the treatment strategy by TCM should be in a close manner and referred to as "treating different diseases by the same treatment." Qishen Yiqi dripping pill is a modern Chinese herbal medicine that has been widely used for the treatment of patients with coronary heart disease characterized as Qi-deficiency and blood stasis in China. Recently, many clinical reports have demonstrated the potential therapeutic effects of Qishen Yiqi dripping pills on ischemic stroke and diabetic nephropathy. Based on these reports, we will summarize the clinical applications of Qishen Yiqi dripping pills on coronary heart disease, ischemic stroke, and diabetic nephropathy, including the involved mechanisms discussed in various research works.

Changes in respiration of the mitochondrial fraction of brain homogenates in rats with stepwise incomplete cerebral ischemia

Objective: to conduct a comparative analysis of mitochondrial respiration in brain homogenates of rats with stepwise incomplete cerebral ischemia (SICI) with varying duration between ligations of both common carotid arteries (CCA). Material and methods. The experiments were performed on 24 male mongrel white rats weighing 260±20 g. All rats were distributed among three subgroups. Cerebral ischemia was simulated under intravenous thiopental anesthesia (40-50 mg/kg). The control group (n=6) comprised sham-operated rats of similar gender and weight. To study mitochondrial respiration, the brain was extracted in the cold environment (0-4 °C), dried with filter paper, weighed and homogenized sensu the modified technique in an isolation medium containing 0.32 M sucrose, 10 mM Tris-HCl, 1 mM EDTA, pH of 7.4 (in a ratio of 1:10), using Potter – Elvehjem homogenizer with Teflon pestle. Results. SICI with an interval of 1 and 3 days between ligation of both CCA led to neuronal damage in the parietal cortex and hippocampus of rats, which manifested itself in a reduction of the neuron size, deformation of the perikaryons, an increase in the number of shrunken neurons and shadow cells. The most pronounced changes were observed in the subgroup with one-day interval between ligations. These changes were similar to the changes in incomplete cerebral ischemia (ICI) (p=0.07), except for the absence of cells with pericellular edema in the hippocampus and a smaller number of those in the parietal cortex. ICI with seven-day interval between ССА ligations, on the contrary, was manifested by less pronounced histological changes, especially in the hippocampus. Conclusion. Comparative analysis of mitochondrial respiration in brain homogenates revealed that the severity of brain damage in SSIC depended on the interval between blood flow arrest in both CCA. At the same time, the highest level of energy metabolism disorder was observed during CCA ligation with an interval of one day, which implied insufficient implementation of compensatory mechanisms.