Enzymes Lactate Dehydrogenase Research Articles

Stem cell biotherapy: A new remedy for Trichinella spiralis-induced inflammatory myopathy.

Trichinella spiralis (T. spiralis)-induced myopathy is an inflammatory myopathy that is difficult to treat unless the parasite is combated in its early intestinal phase before it reaches the muscles. This study aimed to evaluate the effect of local mesenchymal stem cell (MSC) therapy on T. spiralis-induced inflammatory myopathy in rats. Rats were divided into four groups: Group 1 (non-infected non-treated group); Group 2 (infected non-treated group); Group 3 (infected albendazole (ABZ)-treated group); and Group 4 (infected MSC-treated group). Their muscle status was assessed physiologically with the righting reflex and electromyography (EMG), parasitologically with the total muscle larval count, histopathologically with hematoxylin and eosin and Mallory's trichrome stains, as well as immunohistochemically for myogenin as a marker of muscle regeneration. Additionally, serum muscle enzymes creatine kinase (CK) and lactate dehydrogenase (LDH), as well as muscle matrix metalloproteinases MMP1 and MMP9, were assayed. Finally, the immunological response was assessed by measuring the levels of the muscle inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ), and interleukin-4 (IL-4). Our findings revealed that MSC therapy markedly improved muscle EMG and righting reflex, as well as the histopathological appearance of the muscles, reduced inflammatory cellular infiltrates, and increased myogenin immunostaining. It also reduced serum CK and LDH levels, as well as muscle INF-γ, TNF-α, IL-4, MMP1, and MMP9 levels. However, it had no effect on the total muscle larval count. Accordingly, due to its anti-inflammatory properties and muscle-regenerative effect, MSC therapy could be a promising new remedy for T. spiralis-induced myopathy.

Bigel formulations of St. John’s wort extract in wound healing: toxicological aspects

This study aimed to investigate the toxicological profile of hyperforin (HP) in silico and to assess it in vivo after topical application of an HP-rich St. John’s wort (SJW) extract. The former analysis predicted low toxicity because of HP’s inability to bind DNA or proteins, but structural alerts for skin irritation/corrosion, carcinogenicity, and mutagenicity were found. Animal studies involved the treatment of excision wounds in Wistar rats with poloxamer 407/borage oil formulations (bigels; Bs) containing HP-rich SJW extract previously developed by us. The effects of semisolids comprising ‘free’ extract (B/SJW) or extract loaded in nanostructured lipid carriers (B/NLC-SJW) were compared to positive (commercial herbal product) and negative (untreated) controls after 2-, 7-, 14-, and 21-day applications. Malondialdehyde (MDA) and ABTS assays evaluated the degree of oxidative stress—treatment with bigels did not affect MDA favorably but led to an increased radical-cation scavenging capacity (compared to controls). Gamma-glutamyl transferase (GGT), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and lactate dehydrogenase (LDH) enzyme levels were measured as indicators for liver/tissue damage. Treatment with both B/SJW and B/NLC-SJW for 21 days resulted in lower GGT and ASAT levels than those in controls. Two-day application of the biphasic semisolids contributed to normalized ALAT levels (lower than in both negative and positive controls), and the same trends were observed in LDH levels after a 7-day treatment. The promising results obtained after the B/NLC-SJW application suggest that this drug delivery system may not only preserve HP in SJW extract effectively but also ‘expose’ its cyto-/hepatoprotective potential.

Investigating the Toxicity Caused by Photodynamic Therapy with a Low-power Diode Laser with a Wavelength of 810 nm Compared to a Combination of Curcumin in Breast Cancer Cells

Background: Curcumin has low side effects and strong antioxidant, anti-diabetic and anti-cancer activities, and other therapeutic properties. Studies have confirmed that visible light can improve curcumin’s antibacterial, anti-inflammatory, antioxidant, and anti-cancer properties. Objectives: This study aimed to investigate the toxicity caused by photodynamic therapy with a low-power diode laser with a wavelength of 810 nm compared to curcumin in breast cancer cells (MDA-MB-231 cell line). Methods: After culturing cells in a 96-well plate, concentrations of 1, 10, 100, and 500 μM of curcumin alone and also in combination with a low-power diode laser with a wavelength of 810 nm and after 48 hours of incubation, cells’ viability was assessed by MTT method. Also, cell proliferation rate, lactate dehydrogenase enzyme release, and membrane lipid peroxidation were measured. Results: The percentage of survival, cell proliferation rate, and release of lactate dehydrogenase enzyme in the combination of 500 μg/mL with laser was significantly lower than the rest of the groups, while the average concentration of malondialdehyde obtained according to micrograms in the curcumin group with laser was higher than other groups. Conclusions: Overall, combining curcumin with a photodynamic laser may reduce the survival effect and cell proliferation rate of curcumin on MDA cells. Most current research on curcumin combined with photodynamic lasers focuses on in vitro experiments and animal models; however, further clinical research is needed.

The role of lactate dehydrogenase of the pleural liquid in the cytopathological diagnosis

Elevated serum or pleural fluid lactate dehydrogenase (LDH)enzyme levels can be associated with various conditions, including neoplasia, reticuloendothelial tumors, and leukemia. These conditions can lead to cell damage or death, causing LDH to be released into the bloodstream and pleural fluid. An increase in LDH levels may prompt further investigation into the underlying cause, which could include malignancies or other diseases. Elevated LDH levels in pleural fluid are often associated with certain conditions, and our study seeks to establish a quantitative assessment of LDH in conjunction with cytopathological examination for diagnostic purposes. We show here that the presence of abnormal or malignant cells in pleural fluid, as indicated by positive cytopathological results, can be concerning and often necessitates further evaluation. Elevated LDH levels provide biochemical evidence that supports the cytopathological findings, strengthening the case for a potential underlying disease or condition.

Hyperpolarized Carbon 13 MRI: Clinical Applications and Future Directions in Oncology.

Hyperpolarized carbon 13 MRI (13C MRI) is a novel imaging approach that can noninvasively probe tissue metabolism in both normal and pathologic tissues. The process of hyperpolarization increases the signal acquired by several orders of magnitude, allowing injected 13C-labeled molecules and their downstream metabolites to be imaged in vivo, thus providing real-time information on kinetics. To date, the most important reaction studied with hyperpolarized 13C MRI is exchange of the hyperpolarized 13C signal from injected [1-13C]pyruvate with the resident tissue lactate pool. Recent preclinical and human studies have shown the role of several biologic factors such as the lactate dehydrogenase enzyme, pyruvate transporter expression, and tissue hypoxia in generating the MRI signal from this reaction. Potential clinical applications of hyperpolarized 13C MRI in oncology include using metabolism to stratify tumors by grade, selecting therapeutic pathways based on tumor metabolic profiles, and detecting early treatment response through the imaging of shifts in metabolism that precede tumor structural changes. This review summarizes the foundations of hyperpolarized 13C MRI, presents key findings from human cancer studies, and explores the future clinical directions of the technique in oncology. Keywords: Hyperpolarized Carbon 13 MRI, Molecular Imaging, Cancer, Tissue Metabolism © RSNA, 2023.

Attenuation of Oxidative Damage via Upregulating Nrf2/HO-1 Signaling Pathway by Protease SH21 with Exerting Anti-Inflammatory and Anticancer Properties In Vitro.

Oxidative damage and inflammation are among the very significant aspects interrelated with cancer and other degenerative diseases. In this study, we investigated the biological activities of a 25 kDa protease (SH21) that was purified from Bacillus siamensis. SH21 exhibited very powerful antioxidant and reactive oxygen species (ROS) generation inhibition activity in a dose-dependent approach. The mRNA and protein levels of antioxidant enzymes such as superoxide dismutase 1 (SOD1), catalase (CAT), and glutathione peroxidase 1 (GPx-1) were enhanced in the SH21-treated sample. SH21 also increased the transcriptional and translational activities of NF-E2-related factor 2 (Nrf2) with the subsequent development of detoxifying enzyme heme oxygenase-1 (HO-1). In addition, SH21 showed potential anti-inflammatory activity via inhibition of nitric oxide (NO) and proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β, production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. At concentrations of 60, 80, and 100 μg/mL, SH21 potentially suppressed nitric oxide synthase (iNOS) and cytokine gene expressions. Furthermore, SH21 significantly released lactate dehydrogenase (LDH) enzyme in cancer cell supernatant in a concentration-dependent manner and showed strong activity against three tested cancer cell lines, including HL-60, A549, and Hela. Our results suggest that SH21 has effective antioxidant, anti-inflammatory, and anticancer effects and could be an excellent therapeutic agent against inflammation-related diseases.

The effects of acutely elevated ammonia concentrations on haemolymph parameters in the Mediterranean mussel, Mytilus galloprovincialis

In aquaculture systems, ammonia nitrogen is a major component of waste products arising from the metabolism of cultured organisms and can significantly affect the quality of the rearing environment. The purpose of the current study was to determine modulation of the haemocyte population and selected haemolymph biochemical parameters of the Mediterranean mussel Mytilus galloprovincialis (Lamarck, 1919) exposed to acutely elevated ammonia concentrations.In order to investigate the extent and dynamics of an expected reduction of physiological fitness and survival rate of cultured mussels the stress-on-stress test was conducted combining ammonia and air exposure. The latter test illustrated the extent of reduced mussel physiological fitness and survival rate upon 72 h exposure to 10 and 30 mM NH4Cl in experimental tanks followed by additional exposure to air. Mussels cultured for up to 48 h in experimental tanks comprising 5, 10 and 30 mM NH4Cl, revealed dose and time dependent increase in haemolymph enzyme lactate dehydrogenase levels, urea, and uric acid metabolite levels, as well as the corresponding redistribution in haemocyte population profiles, indicating an inherent response of this organism to ammonia. Finally, a significant negative linear correlation between the mussel hyalinocytes subpopulation and the mean urea levels was observed. The obtained result suggests a possible function of basophilic and acidophilic granulocyte subpopulations in ammonia metabolism leading to urea synthesis by means of surplus ammonium ions are sequestered and extracted from the body. Therefore, defined modulation of the mussel haemocyte population structure may serve as an accurate bioindicator of mussels exposure to acutely elevated ammonia concentrations in environmental and aquaculture biomonitoring studies.

Furan promotes cytotoxic effects through DNA damage and cell apoptosis in Leydig cells

Furan is an organic chemical that can cause adverse effects on human health and is formed as a result of the thermal decomposition of many food components during cooking, storage, and processing techniques. Studies have shown that exposure to furan causes nephrotoxicity, hepatotoxicity, immunotoxicity, and reproductive toxicity. According to our current knowledge of the literature, the genotoxic mode of action of furan is highly controversial. The genotoxic effects of furan on the male reproductive system, however, have not been studied. In this study, the TM3 Leydig cell line was treated with 750, 1500, and 3000 μM concentrations of furan for 24 h. Following the completion of the exposure period, the cytotoxicity of furan in TM3 Leydig cells was assessed using a cell viability assay and a spectrophotometric measurement of lactate dehydrogenase (LDH) enzyme levels. The double fluorescence staining method was used to demonstrate furan-induced apoptosis, and DNA damage was shown using the micronucleus, comet, and chromosomal aberration assays. The result indicated that furan administration of Leydig cells resulted in an increase in structural chromosomal aberration, comet, and micronucleus formation, reduced cell viability, increased LDH activity, and a higher incidence of apoptotic cells. These findings revealed that furan induces DNA damage in TM3 Leydig cells, causing genotoxicity and DNA damage-induced cytotoxicity.

In Silico Screening and Molecular Dynamics Simulation of Potential Anti-Malarial Agents from Zingiberaceae as Potential Plasmodium falciparum Lactate Dehydrogenase (PfLDH) Enzyme Inhibitors.

Malaria continues to be a major public health issue in a number of countries, particularly in tropical regions-the emergence of drug-resistant Plasmodium falciparum encourages new drug discovery research. The key to Plasmodium falciparum survival is energy production up to 100 times greater than other parasites, primarily via the PfLDH. This study targets PfLDH with natural bioactive compounds from the Zingiberaceae family through molecular docking and molecular dynamic studies. Sulcanal, quercetin, shogosulfonic acid C, galanal A and naringenin are the Top 5 compounds with a lower binding energy value than chloroquine, which was used as a control in this study. By binding to NADH and substrate binding site residues, the majority of them are expected to inhibit pyruvate conversion to lactate and NAD+ regeneration. When compared to sulcanal and control drugs, the molecular dynamics (MD) simulation study indicated that quercetin may be the most stable molecule when interacting with PfLDH.

Sensitivity of Lewis lung carcinoma cells to glycolysis and glutaminolysis inhibition

Awareness of the key role of metabolic reprogramming in tumor cell progression has promoted the exploration of approaches to inhibit glycolysis to develop novel antitumor therapy. Highly promising in clinical terms is sodium oxamate, an inhibitor of the enzyme lactate dehydrogenase, which is a critical regulator of glycolysis in tumor cells. Therefore, studying the mechanisms of sodium oxamate action is a relevant issue in modern oncology. The purpose of this work was to examine the impact of oxamate on the survival and proliferative activity of Lewis lung carcinoma (LLC) cells under glutamine deficiency. The conducted research has shown that LLC cells exhibit heterogeneity in their sensitivity to the cytostatic/cytotoxic effects of oxamate: approximately 65% of cells are sensitive to its cytostatic/cytotoxic action, while 35% are resistant. In sensitive cells, sodium oxamate exerts a significant cytotoxic effect by activating apoptosis and, probably, by inhibiting the rate of glucose consumption and lactate production by tumor cells. Glutamine deficiency in the nutrient medium significantly increases the cytotoxic effect of sodium oxamate. No significant stimulation of reactive oxygen species production by tumor cells was observed under the influence of oxamate. It was found that sodium oxamate is capable of inducing G2/M cell cycle arrest in LLC cells in the proliferation of Lewis lung carcinoma cells.

Harmful effects of chlorhexidine on hepatic metabolism

Chlorhexidine (CHX) is an over-the-counter antiseptic amply used by the population. There are reports that CHX acts in mitochondria as an uncoupler and inhibitor. The purpose of this study was to investigate the short-term effects of CHX on hepatic metabolic pathways linked to energy metabolism in the perfused rat liver. The compound inhibited both glucose synthesis and the urea cycle. Oxygen consumption was raised at low concentrations (up to 10 μM) and diminished at higher ones. A pronounced diminution in the cellular ATP content was observed. Conversely, CHX stimulated glycolysis and enhanced leakage of cellular enzymes (lactate dehydrogenase and fumarase). In isolated mitochondria, this antiseptic inhibited pyruvate carboxylation, oxidases, and oxygen uptake at very low concentrations (2 μM) and promoted uncoupling. The results described herein raise great concerns about the safety of CHX, as the observed effects can induce hypoglycemia, lactic acidosis, ammonemia as well as cell membrane disruption.

Rosmarinic acid alone or in combination with Lactobacillus rhamnosus ameliorated resistance to ammonia stress in the rainbow trout, Oncorhynchus mykiss: growth, immunity, antioxidant defense and liver functions

Abstract Rosmarinic acid (RS) and Lactobacillus rhamnosus (LR) were added singularly or in combination to rainbow trout (Oncorhynchus mykiss) diets to test their efficacy in the protection against ammonia stress. Fish (31.4±0.6 g) were randomly allocated to six groups in three replicates, as follows: T1: basic food as control, T2: LR with a concentration of 1.5 × 108 CFU /g, T3: LR with a concentration of 3 × 108 CFU/g, T4: 1 g RS/kg, T5: 3 g RS/kg, and T6: 1.5 × 108 CFU/g LR + 1 g RS/kg and T7: 3 × 108 CFU/g LR + 3 g RS/kg. After 60 days feeding, fish were exposed to ammonia stress. After the feeding period, the supplemented fish had the highest final body weight (FW), weight gain (WG), and specific growth rate (SGR), and the lowest feed conversion ratio (FCR) as compared with the control group (P<0.05). Amylase, protease and lipase activities were noticed markedly higher in fish supplemented with 1.5 × 108 CFU/g LR + 1 g RS/kg and 1.5 × 108 CFU/g LR diets compared to the control (P<0.05). Generally, fish in supplemented diets, particularly T2 and T6 groups, had the highest lysozyme, alternative complement activity (ACH50), total Ig, nitroblue tetrazolium test (NBT), myeloperoxidase (MPO), complement component 3 (C3), complement component 4 (C4), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx). On the other hand, T2 and T6 groups had the lowest malondialdehyde (MDA), glucose, and cortisol concentrations as well as alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) enzyme levels when compared with the control (P<0.05). After ammonia stress, fish in the supplemented groups, particularly T2 and T6, generally showed significantly higher values of lysozyme, ACH50, total Ig, NBT, MPO, C3, C4, SOD, CAT, GPx and lower levels of MDA, glucose, cortisol, ALT, ALP, LDH when compared with the control (P<0.05). In conclusion, a combined administration of RS and L. rhamnosus effectively improved growth performance and health status as well as enhanced the resistance of rainbow trout against ammonia toxicity.

Crimean-Congo Hemorrhagic Fever (CCHF)

Crimean-Congo haemorrhagic fever (CCHF) is a viral infection that can kill a lot of people and is found in about 30 countries. It is the most widespread of the medically important diseases caused by ticks and is very close to how Hyalomma spp. ticks are found all over the world. Tick bites, crushing infected ticks, contact with a patient with CCHF during the acute phase of the infection, or contact with blood or tissues from viraemic livestock are all ways in which humans contract the disease. Clinical highlights regularly show an emotional movement described by drain, myalgia, and fever. Lactate dehydrogenase, creatinine phosphokinase, and liver enzymes all rise, and bleeding markers last longer. The endothelium infection is a major pathogen. In finding, protein connected immunoassay and continuous opposite transcriptase PCR are utilized. Early finding is basic for patient treatment and the counteraction of expected nosocomial diseases. The most essential component of case management is supportive therapy. When treating patients who have hemorrhages from the nose, mouth, gums, vagina, and injection sites, healthcare workers run a high risk of infection. Straightforward boundary safety measures have been accounted for to be compelling.

CD19-Targeting CAR T Cells for Myositis and Interstitial Lung Disease Associated With Antisynthetase Syndrome

Autoimmune disorders can affect various organs and if refractory, can be life threatening. Recently, CD19-targeting-chimeric antigen receptor (CAR) T cells were efficacious as an immune suppressive agent in 6 patients with refractory systemic lupus erythematosus and in 1 patient with antisynthetase syndrome. To test the safety and efficacy of CD19-targeting CAR T cells in a patient with severe antisynthetase syndrome, a complex autoimmune disorder with evidence for B- and T-cell involvement. This case report describes a patient with antisynthetase syndrome with progressive myositis and interstitial lung disease refractory to available therapies (including rituximab and azathioprine), who was treated with CD19-targeting CAR T cells in June 2022 at University Hospital Tübingen in Tübingen, Germany, with the last follow-up in February 2023. Mycophenolate mofetil was added to the treatment to cotarget CD8+ T cells, hypothesized to contribute to disease activity. Prior to treatment with CD19-targeting CAR T cells, the patient received conditioning therapy with fludarabine (25 mg/m2 [5 days before until 3 days before]) and cyclophosphamide (1000 mg/m2 [3 days before]) followed by infusion of CAR T cells (1.23×106/kg [manufactured by transduction of autologous T cells with a CD19 lentiviral vector and amplification in the CliniMACS Prodigy system]) and mycophenolate mofetil (2 g/d) 35 days after CD19-targeting CAR T-cell infusion. The patient's response to therapy was followed by magnetic resonance imaging of the thigh muscle, Physician Global Assessment, functional muscle and pulmonary tests, and peripheral blood quantification of anti-Jo-1 antibody levels, lymphocyte subsets, immunoglobulins, and serological muscle enzymes. Rapid clinical improvement was observed after CD19-targeting CAR T-cell infusion. Eight months after treatment, the patient's scores on the Physician Global Assessment and muscle and pulmonary function tests improved, and there were no detectable signs of myositis on magnetic resonance imaging. Serological muscle enzymes (alanine aminotransferase, aspartate aminotransferase, creatinine kinase, and lactate dehydrogenase), CD8+ T-cell subsets, and inflammatory cytokine secretion in the peripheral blood mononuclear cells (interferon gamma, interleukin 1 [IL-1], IL-6, and IL-13) were all normalized. Further, there was a reduction in anti-Jo-1 antibody levels and a partial recovery of IgA (to 67% of normal value), IgG (to 87%), and IgM (to 58%). CD19-targeting CAR T cells directed against B cells and plasmablasts deeply reset B-cell immunity. Together with mycophenolate mofetil, CD19-targeting CAR T cells may break pathologic B-cell, as well as T-cell responses, inducing remission in refractory antisynthetase syndrome.

Assessment of milk and blood enzymes in Holstein cows with subclinical mastitis

The objective of this study was to determine the activities of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the milk and blood of lactating Holstein cows and investigate their association with subclinical mastitis (SCM). This study also aims to evaluate the impact of SCM and its severity based on California mastitis test (CMT) scores on the above mentioned enzymes, as well as to test the efficiency of their use as an early predictive diagnostic tool. Thirty multiparous, lactating dairy Holstein cows were examined using CMT and according to the obtained results classified into four groups; control group 1 (SCM-free = 10, score = 0), group 2 (weak positive = 8, score +1), group 3 (positive = 7, score +2) and group 4 (strong positive = 5, score +3). The milk LDH, ALP, and GGT activities were significantly higher in groups 3 and 4 compared to group 2 and the control group. LDH activity was significantly higher in group 2 compared to the control group. The mean blood LDH and ALP activities in SCM groups were significantly higher than in the control group. ALP blood activity was significantly higher in group 4 compared to group 2. The blood GGT activity was significantly higher in group 4 compared to other groups. There was a significant positive association between milk LDH, ALP, and GGT enzymes as well as the blood enzymes (ALP and GGT) in SCM cows. The results showed that subclinical mastitis causes considerable changes in the activities of enzymes in milk and blood of infected cows.

The mRNA and protein levels of the glycolytic enzymes lactate dehydrogenase A (LDHA) and phosphofructokinase platelet (PFKP) are good predictors of survival time, recurrence, and risk of death in cervical cancer patients.

Patients with cervical cancer (CC) may experience local recurrence very often after treatment; when only clinical parameters are used, most cases are diagnosed in late stages, which decreases the chance of recovery. Molecular markers can improve the prediction of clinical outcome. Glycolysis is altered in 70% of CCs, so molecular markers of this pathway associated with the aggressiveness of CC can be identified. The expression of 14 glycolytic genes was analyzed in 97 CC and 29 healthy cervical tissue (HCT) with microarray; only LDHA and PFKP were validated at the mRNA and protein levels in 36 of those CC samples and in 109 new CC samples, and 31 HCT samples by qRT-PCR, Western blotting, or immunohistochemistry. A replica analysis was performed on 295 CC from The Cancer Genome Atlas (TCGA) database. The protein expression of LDHA and PFKP was associated with poor overall survival [OS: LDHA HR = 4.0 (95% CI = 1.4-11.1); p = 8.0 × 10-3 ; PFKP HR = 3.3 (95% CI = 1.1-10.5); p = 4.0 × 10-2 ] and disease-free survival [DFS: LDHA HR = 4.5 (95% CI = 1.9-10.8); p = 1.0 × 10-3 ; PFKP HR = 3.2 (95% CI = 1.2-8.2); p = 1.8 × 10-2 ] independent of FIGO clinical stage, and the results for mRNA expression were similar. The risk of death was greater in patients with overexpression of both biomarkers than in patients with advanced FIGO stage [HR = 8.1 (95% CI = 2.6-26.1; p = 4.3 × 10-4 ) versus HR = 7 (95% CI 1.6-31.1, p = 1.0 × 10-2 )] and increased exponentially as the expression of LDHA and PFKP increased. LDHA and PFKP overexpression at the mRNA and protein levels was associated with poor OS and DFS and increased risk of death in CC patients regardless of FIGO stage. The measurement of these two markers could be very useful for evaluating clinical evolution and the risk of death from CC and could facilitate better treatment decision making.

The effect of electrical stimulation of skeletal muscle on cardioprotection and on muscle-derived myokine levels in rats: A pilot study.

Electrical muscle stimulation (EMS) is a widely used method in sports and rehabilitation therapies to simulate physical exercise. EMS treatment via skeletal muscle activity improves the cardiovascular functions and the overall physical condition of the patients. However, the cardioprotective effect of EMS has not been proven so far, therefore, the aim of this study was to investigate the potential cardiac conditioning effect of EMS in an animal model. Low-frequency 35-min EMS was applied to the gastrocnemius muscle of male Wistar rats for three consecutive days. Their isolated hearts were then subjected to 30 min global ischemia and 120 min reperfusion. At the end of reperfusion cardiac specific creatine kinase (CK-MB) and lactate dehydrogenase (LDH) enzyme release and myocardial infarct size were determined. Additionally, skeletal muscle-driven myokine expression and release were also assessed. Phosphorylation of cardioprotective signaling pathway members AKT, ERK1/2, and STAT3 proteins were also measured. EMS significantly attenuated cardiac LDH and CK-MB enzyme activities in the coronary effluents at the end of the ex vivo reperfusion. EMS treatment considerably altered the myokine content of the stimulated gastrocnemius muscle without altering circulating myokine levels in the serum. Additionally, phosphorylation of cardiac AKT, ERK1/2, and STAT3 was not significantly different in the two groups. Despite the lack of significant infarct size reduction, the EMS treatment seems to influence the course of cellular damage due to ischemia/reperfusion and favorably modifies skeletal muscle myokine expressions. Our results suggest that EMS may have a protective effect on the myocardium, however, further optimization is required.

The Combined Effect of Taurine and Omega-3 Supplementation on Delayed Onset Muscle Soreness in High-Intensity Eccentric Exercise

Background: Eccentric exercise makes more tensions in active muscle fibers, resulting in muscle damage and delayed pain. Therefore, Delayed-Onset Muscle Soreness (DOMS) is a common result of severe eccentric contractions. This study aimed to clarify the combined effect of taurine and omega-3 supplementation on DOMS and muscle damage after high-intensity eccentric exercise in young untrained men.
 Methods: Forty-eight young untrained males were assigned to four groups (taurine+omega-3 [combined], taurine, omega-3, and one placebo group) and given 1,500 mg taurine and 1,500 mg omega-3 or 1,500 mg taurine or 1,500 mg omega-3 or placebo twice a day respectively. Each group received its supplements for twenty-eight days. DOMS and muscle damage in the lower body developed using a leg press with a weight equivalent to 70% of 1RM (One-Repetition Maximum). Lactate dehydrogenase (LDH), Creatine kinase (CK) and perceived muscle soreness measures were repeated before, immediately, 24, 48, and 72 hr after eccentric activity. p<0.05 was considered to be statistically significant.
 Results: In the combined group, there was no increase in CK and LDH in immediate time and 72 hr after the exercise, respectively, compared to the period before the workout. At 24 and 48 hr after the training, there was a significant decrease in muscle pain perception in all groups compared to placebo (p<0.05).
 Coclusion: A combination of 1500 mg taurine and 1500 mg omega-3, two times a day, for four weeks can reduce the levels of CK and LDH enzymes as some indicators of muscle damage. It also attenuates exercise-induced DOMS and muscle damage.

Skeletal muscle fibre type and enzymatic activity in adult offspring following placental and peripheral malaria exposure in foetal life.

Maternal malaria may restrict foetal growth. Impaired utero-placental blood flow due to malaria infection may cause hypoxia-induced altered skeletal muscle fibre type distribution in the offspring, which may contribute to insulin resistance and impaired glucose metabolism. This study assessed muscle fibre distribution 20 years after placental and/or peripheral in-utero malaria exposure compared to no exposure, i.e., PPM+, PM+, and M-, respectively. We traced 101 men and women offspring of mothers who participated in a malaria chemosuppression study in Muheza, Tanzania. Of 76 eligible participants, 50 individuals (29 men and 21 women) had skeletal muscle biopsy taken from m. vastus lateralis in the right leg. As previously reported, fasting and 30 min post-oral glucose challenge plasma glucose values were higher, and insulin secretion disposition index was lower, in the PPM+ group. Aerobic capacity (fitness) was estimated by an indirect VO2max test on a stationary bicycle. Muscle fibre sub-type (myosin heavy chain, MHC) distribution was analysed, as were muscle enzyme activities (citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase, myophosphorylase, phosphofructokinase, lactate dehydrogenase, and creatine kinase activities. Between-group analyses were adjusted for MHC-I %. No differences in aerobic capacity were found between groups. Despite subtle elevations of plasma glucose levels in the PPM+ group, there was no difference in MHC sub-types or muscle enzymatic activities between the malaria-exposed and non-exposed groups. The current study did not show differences in MHC towards glycolytic sub-types or enzymatic activity across the sub-groups. The results support the notion of the mild elevations of plasma glucose levels in people exposed to placental malaria in pregnancy being due to compromised pancreatic insulin secretion rather than insulin resistance.

ULK1-mediated metabolic reprogramming regulates Vps34 lipid kinase activity by its lactylation.

Autophagy and glycolysis are highly conserved biological processes involved in both physiological and pathological cellular programs, but the interplay between these processes is poorly understood. Here, we show that the glycolytic enzyme lactate dehydrogenase A (LDHA) is activated upon UNC-51-like kinase 1 (ULK1) activation under nutrient deprivation. Specifically, ULK1 directly interacts with LDHA, phosphorylates serine-196 when nutrients are scarce and promotes lactate production. Lactate connects autophagy and glycolysis through Vps34 lactylation (at lysine-356 and lysine-781), which is mediated by the acyltransferase KAT5/TIP60. Vps34 lactylation enhances the association of Vps34 with Beclin1, Atg14L, and UVRAG, and then increases Vps34 lipid kinase activity. Vps34 lactylation promotes autophagic flux and endolysosomal trafficking. Vps34 lactylation in skeletal muscle during intense exercise maintains muscle cell homeostasis and correlates with cancer progress by inducing cell autophagy. Together, our findings describe autophagy regulation mechanism and then integrate cell autophagy and glycolysis.