Lactate Dehydrogenase Activity Levels Research Articles

Interplay between Energy Supply and Glutamate Toxicity in the Primary Cortical Culture.

Limited substrate availability because of the blood-brain barrier (BBB) has made the brain develop specific molecular mechanisms to survive, using lactate synthesized by astrocytes as a source of energy in neurons. To understand if lactate improves cellular viability and susceptibility to glutamate toxicity, primary cortical cells were incubated in glucose- or lactate-containing media and toxic concentrations of glutamate for 24 h. Cell death was determined by immunostaining and lactate dehydrogenase (LDH) release. Mitochondrial membrane potential and nitric oxide (NO) levels were measured using Tetramethylrhodamine, methyl ester (TMRM) and 4-Amino-5-Methylamino-2',7'-Difluorofluorescein Diacetate (DAF-FM) live staining, respectively. LDH activity was quantified in single cells in the presence of lactate (LDH substrate) and oxamate (LDH inhibitor). Nuclei of cells were stained with DAPI and neurons with MAP2. Based on the distance between neurons and glial cells, they were classified as linked (<10 µm) and non-linked (>10 µm) neurons. Lactate increased cell death rate and the mean value of endogenous NO levels compared to glucose incubations. Mitochondrial membrane potential was lower in the cells cultured with lactate, but this effect was reversed when glutamate was added to the lactate medium. LDH activity was higher in linked neurons compared to non-linked neurons, supporting the hypothesis of the existence of the lactate shuttle between astrocytes and at least a portion of neurons. In conclusion, glucose or lactate can equally preserve primary cortical neurons, but those neurons having a low level of LDH activity and incubated with lactate cannot cover high energetic demand solely with lactate and become more susceptible to glutamate toxicity.

A Comparative Study of Vitamin D Level and Lactate Dehydrogenase Activity in Relation to Oxidative Stress in Women with Osteoporosis

Background: Osteoporosis (OP) is a silent disease that affects the microarchitecture of the skeleton bones, leading to a drop in mineral levels and an increase in fracture rates. This condition is more common in women than men, especially postmenopausal women, due to decreased production of estrogen, a hormone that regulates bone formation and bone resorption. Oxidative stress is a known factor in the development of OP, resulting from an imbalance in the production of oxidants and antioxidants. Hip and arm fractures are particularly common in women with OP. Objective: The study aimed to evaluate the activity of Lactate Dehydrogenase (LDH) and oxidative stress (OS) levels in postmenopausal women with osteoporosis and varying levels of vitamin D, and to compare these groups based on the measured parameters. Subjects and Methods: This study was conducted at the Baquba Teaching Hospital in Diyala, Iraq, from October 2022 to January 2023. The study involved 100 women whom were divided into two groups, 50 with normal vitamin D levels and 50 with abnormal vitamin D levels. The malondialdehyde (MDA) level was evaluated using the Satoh-modified approach. Results: According to the statistical analysis conducted with the SPSS program, there was a significant difference (P&lt;0.001) in Vitamin D levels between the groups (OPn. D) and (OPab.D). Additionally, significant increases were observed in LDH activity (P&lt;0.001) and MDA levels (P&lt;0.05) for the group (OPab.D) in comparison to (OPn. D). Conclusion: The current study has indicated that women suffering from osteoporosis (OP) have higher levels of LDH and MDA. Additionally, there is an inverse correlation between vitamin D and these two variables; this correlation suggests that vitamin D may possess antioxidant properties that reduce the effects of oxidative stress (OS) in the body. Therefore, vitamin D may help in reducing LDH levels.

"Therapeutic Modulation of Lactate Dehydrogenase Activity Level in Algerian Patients with COVID-19 Infection Associated with Diabetes, Hypertension and Cardiovascular Disease"

"Therapeutic Modulation of Lactate Dehydrogenase Activity Level in Algerian Patients with COVID-19 Infection Associated with Diabetes, Hypertension and Cardiovascular Disease"

Cytoprotective role of human dental pulp stem cell-conditioned medium in chemotherapy-induced alopecia

BackgroundChemotherapy-induced alopecia (CIA) is a distressing adverse effect of chemotherapy, with an estimated incidence of 65% and limited treatment options. Cyclophosphamide (CYP) is a common alopecia-inducing chemotherapy agent. Human dental pulp stem cells (DPSCs) secrete several paracrine factors that up-regulate hair growth. Conditioned medium (CM) collected from DPSCs (DPSC-CM) promotes hair growth; culturing mesenchymal stem cells under hypoxic conditions can enhance this effect.MethodsThe effect of DPSC-CM cultured under normoxic (N-) and hypoxic (H-) conditions against CYP-mediated cytotoxicity in keratinocytes was examined using cell viability assay, lactate dehydrogenase (LDH) cytotoxicity assay, and apoptosis detection. The damage-response pathway was determined in a well-established CIA mouse model by analyzing macroscopic effects, histology, and apoptosis. Reverse transcription-quantitative PCR and Caspase-3/7 activity assay were used to investigate the impact of DPSC-CM on the molecular damage-response pathways in CYP-treated mice. The effect of post-CIA DPSC-CM application on post-CIA hair regrowth was analyzed by macroscopic effects and microstructure observation of the hair surface. Furthermore, to investigate the safety of DPSC-CM as a viable treatment option, the effect of DPSC-CM on carcinoma cell lines was examined by cell viability assay and a subcutaneous tumor model.ResultsIn the cell viability assay, DPSC-CM was observed to increase the number of keratinocytes over varying CYP concentrations. Furthermore, it reduced the LDH activity level and suppressed apoptosis in CYP-treated keratinocytes. DPSC-CM exhibited the cytoprotective role in vivo via the dystrophic anagen damage-response pathway. While both N-CM and H-CM downregulated the Caspase-3/7 activity level, H-CM downregulated Caspase-3 mRNA expression. The proportion of post-CIA H-CM-treated mice with > 90% normal hair was nearly twice that of vehicle- or N-CM-treated mice between days 50 and 59 post-depilation, suggesting that post-CIA H-CM application may accelerate hair regrowth and improve hair quality. Furthermore, DPSC-CM suppressed proliferation in vitro in certain carcinoma cell lines and did not promote the squamous cell carcinoma (SCC-VII) tumor growth rate in mice.ConclusionsThe potentiality of DPSC-CM and H-CM as a promising cytoprotective agent and hair regrowth stimulant, respectively, for CIA needs in-depth exploration.

Long-term consequences of acute toxic prenatal hypoxia induced by sodium nitrite in rat experiments

Introduction. Gestational hypoxia plays an important role in fetal development, as it causes the development of oxidative stress and delayed psychomotor development. The aim of the study was to evaluate the prenatal effect of sodium nitrite on indices characterizing orienting and exploratory activity, mental activity and the degree of hypoxia in rat offspring. Materials and methods. Acute hypoxia was modeled by administration of sodium nitrite at a dose of 30 mg/kg intramuscularly to five pregnant rats during 16–19 days of gestation. Five females constituted a control group. In 50 born rats, orientation and exploration activity, cognitive functions, intensity of lipid peroxidation and glycolysis were studied. Results. The offspring of females that underwent acute hypoxia significantly lagged behind in the positive dynamics of body weight gain compared to control individuals. Thirty-day-old rats showed a pronounced disorder of the structure of behavioral pattern, learning process and long-term memory, increased content of diene conjugates, malonic dialdehyde and the level of lactate dehydrogenase activity in blood. Discussion. It was found that offspring whose mothers suffered acute hypoxia of toxic genesis developed pronounced behavioral disorders of psychomotor agitation and cognitive dysfunction characterized by decreased learning ability and impaired long-term memory. The content of primary and secondary products of lipid peroxidation and lactate dehydrogenase was increased in rats. The development of cellular oxidative stress under conditions of intrauterine hypoxia leads to oxygen deficiency in the fetus and a switch from tissue respiration to glycolysis, which underlies CNS damage. Conclusion. It was shown that sodium nitrite administration during the period from the 16th to the 19th day of gestation caused hyperactivity, depressed emotional status, and decreased orienting and exploratory activity and the ability to learn and retain a memory trace in rat offspring. Increased levels of diene conjugates and malonic dialdehyde, lactate dehydrogenase activity were observed in rats.

The Comparison of the Anti-inflammatory Efficacy of Phytochemical Extracts in Punica granatum and Lawsonia inermis Among Patients Diagnosed With Chronic Periodontitis.

Introduction The oral cavity is the gateway to the human body. Periodontitis is a common inflammatory condition affecting the oral cavity and a known etiological cause of tissue destruction, discomfort, and halitosis. Pomegranate (Punica granatum)and henna (Lawsonia inermis) are herbs known to mankind from timeimmemorial whose extracts are proven to fight inflammation. The current study was done to evaluate the phytochemical anti-inflammatory efficacy of Punica and Lawsonia in patients with chronic periodontitis and test the potency of herbal mouthwashes in fighting the inflammatory condition affecting the oral cavity using distilled water as a control group. Materials and methods A double-blinded randomized control trial was conducted on 60 patients who were recruited and divided into three groups, in which 20 patients were prescribed with pomegranate (Punica: n=20) mouthwash and 20 patients with henna (Lawsonia: n=20) mouthwash along with distilled water (n=20). All patients were randomly allocated using the coin toss methodand advised to use the prescribed mouthwash for a period of two weeks. Unstimulated saliva was collected before using the mouthwash, and salivary enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) and their levels were assessed spectrometrically using the infrared spectrophotoscopy (IFSC) method. Each patientwas assigned a mouthwash and recalled after two weeks. Unstimulated saliva was again collected, and salivary activity levels of enzymes AST, ALT, and LDH were analyzed after using mouthwash in a similar method as done before. Later on, the salivary levels of enzymes AST, ALT, and LDH were compared before and after the usage of mouthwashes. Statistical significance was seen in the salivary enzymatic activity of AST, ALT, and LDH before and after using Punica and Lawsonia mouthwashes due to their potent phytochemical action in fighting inflammation. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS)22 (IBM SPSS Statistics, Armonk, NY). The Shapiro-Wilk test was used to determine the normality and significance; intragroup comparison was done using the Wilcoxon signed-rank test and Mann-Whitney U test. Intergroup comparison was done using the Kruskal-Wallis test. Results Punica patients had much lower levels ofsalivary AST and ALT (p<0.001) and a decrease in LDH (p=0.002) after the usage of mouthwash for a period of two weeks. Also, patients using Lawsonia as herbal mouthwash had reduction in the values of AST (p=0.001) and LDH (p=0.003) and prominent reduction in ALT (p<0.001) aftera period of two weeks. But in the case of patients using distilled water, there was an increase in the salivary enzymatic activity of AST and ALT, which was statistically significant (p<0.001), and LDH (p=0.006)depicting the disease progression even after using mouthwash for the given time period of two weeks. Conclusion This study demonstrated that both Punica and Lawsonia were effective in reducing the inflammation in patients diagnosed with chronic periodontitis. However, when intergroup comparison was done, the anti-inflammatory efficacy was superior in Punica with significant reductionin the parameters such as ofAST, ALT, and LDHwhen compared to Lawsoniaowing to its potent phytochemical constituency in cutting down the inflammation. Hence,Punica can be used as an implicatedeffective anti-inflammatory herbal mouthwash.

Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1.

Norepinephrine (NE) has a certain effect on the improvement of renal function. However, whether NE can alleviate cyclosporin A (CsA)-induced nephrotoxicity needs further study. The effect of CsA (1.25, 2.5, 5, and 10 μM) on the human renal epithelial cell vitality, lactate dehydrogenase (LDH) activity, apoptosis, and secreted frizzled-related protein 1 (SFRP1) level was examined by cell counting kit-8, enzyme-linked immunosorbent assay, flow cytometer, and western blot. The effect of NE on the LDH activity, apoptosis, and SFRP1 level of human renal epithelial cells induced by CsA was examined again. After silencing of SFRP1 in human renal epithelial cells, the SFRP1 level, cell vitality, and apoptosis were examined again. CsA (1.25, 2.5, 5, and 10 μM) attenuated the cell vitality and SFRP1 level but enhanced the LDH activity and apoptosis in human renal epithelial cells, while the above effects were reversed by NE. Moreover, SFRP1 silencing reversed the regulation of NE on the SFRP1 level, cell vitality, and apoptosis in human renal epithelial cells induced by CsA. In conclusion, NE relieved CsA-induced nephrotoxicity via enhancing the expression of SFRP1.

Knockdown of SHP2 attenuated LPS-induced ferroptosis via downregulating ACSL4 expression in acute lung injury.

Acute lung injury (ALI) is a complex disease with a high mortality. Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) is a protein tyrosine phosphatase that participates in pathogenesis of multiple diseases. Nevertheless, the role of SHP2 in ALI remains unknown. The in vivo and in vitro lipopolysaccharide (LPS)-induced ALI models were successfully established. The histopathological changes were evaluated by hematoxylin and eosin staining. The vascular permeability of lungs was assessed by Evans blue assay. The expression of ACSL4 and SHP2 was detected by western blot and qRT-PCR assay. The lactate dehydrogenase (LDH) activity, malondialdehyde (MDA), iron, and glutathione (GSH) levels were measured by commercial kits. The SHP2 was upregulated in LPS-induced ALI mice and LPS-stimulated MLE-12 cells. In loss-of function experiment, the knockdown of SHP2 attenuated LPS-induced lung injury, microvessels damage, pulmonary edema, and increase of lung vascular permeability in vivo. Mechanically, shSHP2-rescued LPS induced increase in LDH activity, MDA, and iron levels, and decrease in GSH levels, as well as the accumulation of reactive oxygen species in vivo and in vitro, leading to an alleviation of LPS-induced ferroptosis. Notably, shSHP2 reduced the expression of Acyl-CoA synthetase long-chain 4 (ACSL4). In the rescued experiments, overexpression of ACSL4 abolished the shSHP2-induced reduction of LDH activity, MDA, and iron levels, and increase in GSH levels, thereby aggravating the LPS-induced ferroptosis. These findings concluded that the knockdown of SHP2 attenuated LPS-induced ferroptosis via downregulation of ACSL4 expression in ALI, providing a novel sight for ALI treatment.

Assessment of WBCs, CRP, LDH and other Biomarkers of Moderate and Severe COVID-19 Patients in Iraq

Background:&#x0D; Though most Iraqi patients who are infected by COVID-19 only suffering from mild symptoms, but in some cases a patient’s condition deteriorates, leading to a negative outcome. This study aims to assess the clinical laboratory features of moderate and severe COVID-19 patients&#x0D; Methods: &#x0D; One hundred diagnosed as moderate and severe COVID-19 patients as well as fifty healthy participants were involved in our current study. Assessment was made for WBCs, Monocytes, Lymphocyte, and Platelets. In addition, serum levels of lactate dehydrogenase (LDH) and C-reactive protein (CRP). &#x0D; Results: &#x0D; A hundred patients aged 33 to 70 years with COVID-19 had severe and moderate cases. Present in DAR AL-SALAM for COVID-19 isolation in Baghdad, Iraq. COVID-19 patients showed increased serum levels LDH and CRP as well as WBCs count and others when compared to healthy individuals. The severe group showed a statistically significant increase in WBCs account, neutrophil activity and LDH levels, compared with moderate group. While the moderate COVID-19 groups displayed a significant rise in lymphocytes activity, CRP, and Platelet. Conclusion: &#x0D; The current investigation found that WBC count, lymphocyte count, LDH activity, and CRP level were effective indicators for determining the severity of COVID-19, making them good assessment indicators.

Predator effects on behavior and anaerobic capacity in the common acorn barnacle (Balanus glandula)

ABSTRACT Differences in the stress experience of sessile organisms across the intertidal zone can differentially influence phenotype. For example, Balanus glandula barnacles from the low intertidal zone have higher lactate levels, greater lactate dehydrogenase (LDH) activity and reduced cirral activity compared to conspecifics from the high intertidal zone. We tested the hypothesis that enhanced anaerobic capacity in lower intertidal B. glandula results from increased predation and hypoxia-inducing shell closure. To investigate this hypothesis, we compared the density of whelk predators across the intertidal zone, and quantified the behavioral response and LDH activity levels of B. glandula exposed to predators in the lab. We consistently found more predators in the low intertidal zone, although the response of B. glandula to predators was short-term operculum closure (<1hr) which did not result in significant differences in LDH activity. Thus, increased predation is not the cause of high anaerobic capacity in lower intertidal B. glandula.

The Chemical Composition Characteristics and Health Risk Assessment of Cooking Fume Condensates from Residential Kitchens in Different Regions of China

The aim of this study was to explore the similarities and differences of volatile organic pollutants (VOCs) in cooking fumes (COF) of residential buildings in different regions of China, as well as to evaluate their potential health risks. COF condensates were collected from 10 representative cities in China and analyzed by a GC-MS method. Their effects on α-glucosidase, acetylcholinesterase (AchE), and lactate dehydrogenase (LDH) activities were then detected to evaluate potential health risks. A total of 174 kinds of VOCs, including aldehydes, esters, hydrocarbons, alcohols, and carboxylic acid, were identified. There were 59 identical compounds in the northern and southern regions, and 56 common compounds in spicy and non-spicy regions. Health risk assessment results showed that COF condensate could inhibit the activity of α-glucosidase to varying degrees (61.73-129.25%), suggesting that it had a potential risk of causing hypoglycemia. Daily and 3 and 6 month intakes of COF in minors, adults, and the elderly had both activated and inhibited effects on AchE. The activated effect in the southern and spicy areas was higher than that in northern and non-spicy areas, revealing that different regions and dietary habits had different effects on the risk of neurological diseases caused by changes in AchE activity. For minors, adults, and the elderly, COF had different degrees of activation of LDH at different exposure times and regions. Activation in the northern and non-spicy areas was higher than that in southern and spicy areas, suggesting that the health risks caused by changes in LDH activity levels were significantly increased.

Increasing the functional capabilities of Mixed Martial Arts athletes in the process of optimizing different regimes of power load

Background and Study Aim. To study the influence of power load regimes different in energy supply and intensity on functional capabilities of Mixed Martial Arts (MMA) athletes.&#x0D; Material and Methods. We examined 75 men aged 19±0.7 who had been practicing MMA for 4±0.8 years. The athletes were divided into 3 groups, 25 participants in each group. The study participants used power load regimes of different intensity in conditions of anaerobic-glycolytic and anaerobic-alactate energy supply of muscle activity. The study lasted 12 weeks. To assess the functional capabilities of athletes in these conditions we used the method of maximum strength development (1 RM). Control of biochemical blood parameters (creatinine, lactate dehydrogenase, testosterone) allowed determining features of adaptive and compensatory body reactions in response to loads.&#x0D; Results. During the study the 3rd group athletes showed the most pronounced increase (by 40.1%; р&lt;0.05) in strength capabilities development. These changes were observed in conditions of anaerobic-alactate mechanism of energy supply. The smallest dynamics in the studied indicators was fixed in group 1 athletes. They used low-intensity training loads in conditions of anaerobic-glycolytic mechanism of energy supply. The results of laboratory studies showed different changes in the studied biochemical parameters of blood. The basal creatinine level in group 3 athletes was 12 times higher than in group 1 athletes. Lactate dehydrogenase (LDH) activity in group 1 athletes increased by 10 times in response to physical load compared to group 3 results. The basal level of LDH activity increased in group 1 (by 14.6%) and 2 (by 6.7%) athletes. The basal testosterone level increased in athletes of group 3 (by 14.4%) and 2 (by 5.6%). The basal level of the studied hormone had no changes in group 1 representatives.&#x0D; Conclusions. Accelerated increase in functional capabilities of MMA athletes was observed during high-intensity power loads in conditions of anaerobic-alactate energy supply mechanism. Using this power load regime will strengthen the adaptive body reserves of athletes at the stage of specialized basic training. Determining characteristics in the studied biochemical indicators in response to stress stimuli will allow to optimize training load regimes. The changes in these indicators will also allow to improve strength training in MMA in the shortest possible time.

Hazelnut Skin in Ewes' Diet: Effects on Colostrum Immunoglobulin G and Passive Transfer of Immunity to the Lambs.

Passive immunity transfer has a pivotal role in newborn lambs, where the colostrum represents the primary source of immunoglobulins. This study hypothesized that the high content in polyphenolic compounds, mono- and poly-unsaturated fatty acids, and vitamin E of hazelnut skin affects blood and colostrum immunoglobulin G (IgG) concentration and related gamma-glutamyl-transferase (GGT) and lactate dehydrogenase (LDH) levels in sheep and their lambs. In the last 45 days of pregnancy, ewes were divided into a control (CTR) and a hazelnut skin supplemented group (HZN). Blood and colostrum were collected from ewes and lambs before the first suckling, at 24 and 48 h after birth, then IgG concentration, GGT and LDH activity levels were measured. IgG concentration in the colostrum and in lamb's serum were significantly greater in HZN than CTR. No significant difference was detected for ewe's blood. A significant positive correlation was found between IgG and GGT in lambs' serum and colostrum, between IgG and LDH, as well as between GGT and LDH in lambs' serum and colostrum. Our results suggest that hazelnut skin supplementation influences IgG colostrum concentration, with improved immune passive transfer to the suckling lambs. The transfer of maternal derived immune factors is confirmed by the GGT and LDH enzyme activity levels.

Protective effects of curcumin/cyclodextrin polymer inclusion complex against hydrogen peroxide-induced LO2 cells damage.

The objective of the present study was to explore the protective effects of the curcumin/cyclodextrin polymer (CUR/CDP) inclusion complex on hydrogen peroxide (H2O2)‐induced LO2 cells damage. In this study, a H2O2‐induced cells oxidative injury model was established to test the protective effects of the CUR/CDP inclusion complex. The cell viability of cells was detected by the thiazolyl blue tetrazolium bromide (MTT) assay. The extracellular lactate dehydrogenase (LDH) activity, catalase (CAT) activity, and malondialdehyde (MDA) level were detected by assay kits. The cellular reactive oxygen species (ROS) level was detected using the dichlorodihydrofluorescein (DCF) fluorescence assay. Western blotting analysis was conducted to assess the changes of phosphorylated‐p53 and caspase‐3. The results showed that 700 μM H2O2‐treated LO2 cells for 3 h resulted in a significant decrease of cell viability to 53.00 ± 1.68%, which established the cell oxidative injury model. Cells treated with H2O2 led to a significant increase of extracellular LDH activity, MDA content, and ROS level, and decreased CAT activity. Treatment with CUR/CDP significantly reversed the changes of the above indicators. Moreover, CUR/CDP treatment at 20 and 40 μg/ml inhibited H2O2‐induced increase in phosphorylated‐p53 and caspase‐3 expression, indicating that CUR/CDP suppressed cell apoptosis to alleviate liver injury. The results of those studies demonstrated that CUR/CDP had a protective effect on the oxidative damage of LO2 cells, and it could be developed as a new type of natural liver protection product to apply in the prevention of liver injury.

Apigenin induces oxidative stress in mouse Sertoli TM4 cells.

Background and Aim:Apigenin (API) is an estrogenic compound found in many plants. Sertoli cells reside in the testis and are a key target of environmental toxicants. This study aimed to examine the cytotoxicity, especially oxidative stress of API in mouse Sertoli TM4 cells.Materials and Methods:Mouse Sertoli TM4 cells were treated with 50 and 100 μM API for 48 h. Cell viability, lactate dehydrogenase (LDH) activities, glutathione reductase (GR) activities, production of reactive oxygen species (ROS), and malondialdehyde (MDA) levels were evaluated using various assays.Results:Treatment with API at both 50 and 100 μM decreased viability and GR activity but increased LDH activity, ROS production, and MDA levels in mouse Sertoli TM4 cells.Conclusion:Exposure to API induced oxidative stress in mouse Sertoli TM4 cells.

Lactate Dehydrogenase A or B Knockdown Reduces Lactate Production and Inhibits Breast Cancer Cell Motility in vitro.

Background: Lactate dehydrogenase (LDH) plays an important role in cancer pathogenesis and enhanced expression/activity of this enzyme has been correlated with poor prognosis. In this study we determined the expression profile of LDH-A and B in normal as well as in endocrine-resistant and -responsive breast cancer cells and the effect of their knockdown on LDH activity, lactate production, proliferation and cell motility. Methods: Knockdown experiments were performed using siRNA and shRNA. The expression profile of LDH and signaling molecules was determined using PCR and western blotting. Intracellular LDH activity and extracellular lactate levels were measured by a biochemical assay. Cell motility was determined using wound healing, while proliferation was determined using MTT assay. Results: LDH-A was expressed in all of the tested cell lines, while LDH-B was specifically expressed only in normal and endocrine-resistant breast cancer cells. This was correlated with significantly enhanced LDH activity and lactate production in endocrine resistant breast cancer cells when compared to normal or endocrine responsive cancer cells. LDH-A or -B knockdown significantly reduced LDH activity and lactate production, which led to reduced cell motility. Exogenous lactate supplementation enhanced cell motility co-incident with enhanced phosphorylation of ERK1/2 and reduced E-cadherin expression. Also, LDH-A or -B knockdown reduced ERK 1/2 phosphorylation. Conclusion: Enhanced cell motility in endocrine resistant breast cancer cells is at least in part mediated by enhanced extracellular lactate levels, and LDH inhibition might be a promising therapeutic target to inhibit cancer cell motility.

Water-in-Water Emulsions, Ultralow Interfacial Tension, and Biolubrication

Water-in-Water Emulsions, Ultralow Interfacial Tension, and Biolubrication

Effects of aerobic interval training on myocardial oxidative stress and inflammation in rats with myocardial infarction and its mechanism

Objective: The present study was to determine the effects of aerobic interval training (AIT) on the expressions of SIRT1, Nox4 and inflammatory factor in the heart of rats with myocardial infarction (MI). Methods: Male Sprague Dawley rats were randomly divided into sham-operated group (C), sedentary MI group (MI) and MI with AIT group (ME) (n=10). The MI model was established by ligation the left anterior descending coronary artery. Rats in C groups were subjected to the same surgery, but only threaded and not ligated. After surgery 1 week, rats in ME groups took adaptability training for 1 week, and then subjected to 4 weeks treadmill exercise training. After training, the hearts were collected for histological observation. The level of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in heart was assessed by ultraviolet spectrophotometry. The activity of lactate dehydrogenase (LDH) was determined by enzyme linked immunosorbent assay. The expression of sirtuin1 (SIRT1) mRNA was examined by real-time quantitative polymerase chain reaction (RT-qPCR). The protein expressions of SIRT1, NADPH oxidase 4 (Nox4), tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) were detected by Western blotting. The levels of reactive oxygen species (ROS) were detected by dihydroethidium (DHE) staining. Results: Compared with the C group, the expression level of cardiac Nox4 protein was increased (P＜0.01), the level of MDA, activity of LDH and the level of ROS were increased significantly (P＜0.01), and the expressions of TNF-α and IL-1β protein were augmented in the heart of rats with MI (P＜0.01). However, the expressions of SIRT1 mRNA and protein and the activity of SOD were obviously decreased in MI group (P＜0.01). Furthermore, compared with the MI group, AIT increased the expressions of SIRT1 mRNA and protein and the activity of SOD in the heart of ME group (P＜0.01); Meanwhile, the expressions of cardiac Nox4, MDA level, LDH activity and ROS level were diminished in ME group (P＜0.01) as well as the decreased expressions of TNF-α and IL-1β protein (P＜0.01). SIRT1 expression was negatively related to the expressions of NOX4 and ROS. Conclusion: AIT obviously inhibited myocardial oxidative stress and inflammatory reaction, improved cardiac function in rats with MI, and the mechanism was closely related to the activation of SIRT1-Nox4-ROS signaling pathway.

ROS and metabolomics-mediated autophagy in rat's testicular tissue alter after exercise training; Evidence for exercise intensity and outcomes

AimsOxidative damage and altered metabolic reactions are suspected to initiate the autophagy. The exercise training significantly impacts testicular antioxidant and metabolic potentials. However, the underlying mechanism(s) that the exercise-induced alterations can affect the autophagy markers remained unknown. This study explored the effect of exercise training on antioxidant and metabolic statuses of testicular tissue and uncovered the possible cross-link between these statuses and autophagy-inducers expression. Main methodsWistar rats were divided into sedentary control, low (LICT), moderate (MICT), and high (HICT) intensity continuous training groups. Following 8 weeks of training, the testicular total antioxidant capacity (TAC), total oxidant status (TOS), glutathione (GSH), and NADP+/NADPH as oxidative biomarkers along with intracytoplasmic carbohydrate and lipid droplet patterns, lactate dehydrogenase (LDH) activity, and lactate as metabolic elements were assessed. Finally, the autophagy-inducers expression and sperm count were examined. Key findingsWith no significant impact on the oxidative biomarkers and metabolic elements, the LICT and MICT groups exhibited statistically unremarkable (p < 0.05) impacts on spermatogenesis differentiation, spermiogenesis ratio, and sperm count while increased the autophagy-inducers expression. Reversely, the HICT group, simultaneous with suppressing the antioxidant biomarkers (TAC↓, GSH↓, TOS↑, NADP+/NADPH↑), significantly (p < 0.05) reduced the testicular LDH activity and lactate level, changed the intracytoplasmic carbohydrate and lipid droplet's pattern, and amplified the classical autophagy-inducers p62, Beclin-1, autophagy-related gene (ATG)-7, and light chain 3 (LC3)-II/I expression. SignificanceThe autophagy-inducers overexpression has occurred after HICT induction, most probably to eliminate the oxidative damage cargoes, while increased to maintain the metabolic homeostasis in the LICT and MICT groups.

Hyperpolarized 13C Magnetic Resonance Spectroscopic Imaging of Pyruvate Metabolism in Murine Breast Cancer Models of Different Metastatic Potential.

This study uses dynamic hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopic imaging (MRSI) to estimate differences in glycolytic metabolism between highly metastatic (4T1, n = 7) and metastatically dormant (4T07, n = 7) murine breast cancer models. The apparent conversion rate of pyruvate-to-lactate (kPL) and lactate-to-pyruvate area-under-the-curve ratio (AUCL/P) were estimated from the metabolite images and compared with biochemical metabolic measures and immunohistochemistry (IHC). A non-significant trend of increasing kPL (p = 0.17) and AUCL/P (p = 0.11) from 4T07 to 4T1 tumors was observed. No significant differences in tumor IHC lactate dehydrogenase-A (LDHA), monocarboxylate transporter-1 (MCT1), cluster of differentiation 31 (CD31), and hypoxia inducible factor-α (HIF-1α), tumor lactate-dehydrogenase (LDH) activity, or blood lactate or glucose levels were found between the two tumor lines. However, AUCL/P was significantly correlated with tumor LDH activity (ρspearman = 0.621, p = 0.027) and blood glucose levels (ρspearman = −0.474, p = 0.042). kPL displayed a similar, non-significant trend for LDH activity (ρspearman = 0.480, p = 0.114) and blood glucose levels (ρspearman = −0.414, p = 0.088). Neither kPL nor AUCL/P were significantly correlated with blood lactate levels or tumor LDHA or MCT1. The significant positive correlation between AUCL/P and tumor LDH activity indicates the potential of AUCL/P as a biomarker of glycolytic metabolism in breast cancer models. However, the lack of a significant difference between in vivo tumor metabolism for the two models suggest similar pyruvate-to-lactate conversion despite differing metastatic potential.