Enzymes Of Energy Metabolism Research Articles

Advances in myocardial energy metabolism: metabolic remodeling in heart failure and beyond.

The very high energy demand of the heart is primarily met by ATP production from mitochondrial oxidative phosphorylation, with glycolysis providing a smaller amount of ATP production. This ATP production is markedly altered in heart failure, primarily due to a decrease in mitochondrial oxidative metabolism. Although an increase in glycolytic ATP production partly compensates for the decrease in mitochondrial ATP production, the failing heart faces an energy deficit, that contributes to the severity of contractile dysfunction. The relative contribution of the different fuels for mitochondrial ATP production dramatically changes in the failing heart, which depends to a large extent on the type of heart failure. A common metabolic defect in all forms of heart failure (including HFrEF, HFpEF, and diabetic cardiomyopathies) is a decrease in mitochondrial oxidation of pyruvate originating from glucose (i.e. glucose oxidation). This decrease in glucose oxidation occurs regardless of whether glycolysis is increased, resulting in an uncoupling of glycolysis from glucose oxidation that can decrease cardiac efficiency. The mitochondrial oxidation of fatty acids by the heart increases or decreases, depending on the type of heart failure. For instance, in HFpEF and diabetic cardiomyopathies myocardial fatty acid oxidation increases, while in HFrEF myocardial fatty acid oxidation either decreases or remains unchanged. The oxidation of ketones (which provides the failing heart with an important energy source) also differs depending on the type of heart failure, being increased in HFrEF, and decreased in HFpEF and diabetic cardiomyopathies. The alterations in mitochondrial oxidative metabolism and glycolysis in the failing heart are due to transcriptional changes in key enzymes involved in the metabolic pathways, as well as alterations in redox state, metabolic signaling, and posttranslational epigenetic changes in energy metabolic enzymes. Of importance, targeting the mitochondrial energy metabolic pathways has emerged as a novel therapeutic approach to improving cardiac function and cardiac efficiency in the failing heart.

Alterations in cellular metabolic pathway and epithelial cell maturation induced by MYO5B defects are partially reversible by LPAR5 activation.

Functional loss of the motor protein, Myosin Vb (MYO5B), induces various defects in intestinal epithelial function and causes a congenital diarrheal disorder, microvillus inclusion disease (MVID). Utilizing the MVID model mice, Vil1-CreERT2;Myo5bflox/flox (MYO5B∆IEC) and Vil1-CreERT2;Myo5bflox/G519R (MYO5B(G519R)), we previously reported that functional MYO5B loss disrupts progenitor cell differentiation and enterocyte maturation that result in villus blunting and deadly malabsorption symptoms. In this study, we determined that both absence and a point mutation of MYO5B impair lipid metabolism and alter mitochondrial structure, which may underlie the progenitor cell malfunction observed in MVID intestine. Along with a decrease in fatty acid oxidation, the lipogenesis pathway was enhanced in the MYO5B∆IEC small intestine. Consistent with these observations in vivo, RNA-sequencing of enteroids generated from the two MVID mouse strains showed similar downregulation of energy metabolic enzymes, including mitochondrial oxidative phosphorylation genes. In our previous studies, lysophosphatidic acid (LPA) signaling ameliorates epithelial cell defects in MYO5B∆IEC tissues and enteroids. The present study demonstrated that the highly soluble LPAR5-preferred agonist, Compound-1, improved sodium transporter localization and absorptive function, and tuft cell differentiation in patient-modeled MVID animals that carry independent mutations in MYO5B. Body weight loss in male MYO5B(G519R) mice was ameliorated by Compound-1. These observations suggest that Compound-1 treatment has a trophic effect on intestine with MYO5B functional loss through epithelial cell-autonomous pathways that can accelerate the differentiation of progenitor cells and the maturation of enterocytes. Targeting LPAR5 may represent an effective therapeutic approach for treatment of MVID symptoms induced by different point mutations in MYO5B.

Change in Activities of Enzymes of Energy and Carbohydrate Metabolism in Pink Salmon Oncorhynchus gorbuscha (Walb.) Smolts with Change in Environmental Salinity.

Activities of key enzymes of energy and carbohydrate metabolism (cytochrome c oxidase (COX), lactate dehydrogenase (LDH), aldolase, glucose 6-phosphate dehydrogenase (G6PDH), and 1-glycerophosphate dehydrogenase (1-GPDH)) were studied in pink salmon Oncorhynchus gorbuscha (Walb.) smolts from the White Sea in a cage experiment simulating the transition from a freshwater to a marine environment. A decrease in COX, G6PDH, and 1-GPDH activities and an increase in LDH and aldolase activities were observed in juveniles with an increase in water salinity. Based on the findings, a redistribution of energy substrates between the reactions of aerobic and anaerobic metabolism towards higher anaerobic ATP synthesis was assumed for pink salmon. This may indicate that adaptive mechanisms rearrange metabolism to provide energy for osmoregulation in pink salmon juveniles when the salinity changes in their habitat.

Knockout of <i>Hsp70</i> genes modulates age-related transcriptomic changes in leg muscles, reduces locomotion speed and lifespan of <i>Drosophila melanogaster</i>

The study investigated the effect of knockout of six Hsp70 genes (orthologues of the mammalian genes Hspa1a, Hspa1b, Hspa2 and Hspa8) on age-related changes in gene expression in the legs of Drosophila melanogaster, which contain predominantly skeletal muscle bundles. For this, the leg transcriptomic profile was examined in males of the w1118 control line and the Hsp70– line on the 7th, 23rd and 47th days of life. In w1118 flies, an age-related decrease in the locomotion (climbing) speed (a marker of functional state and endurance) was accompanied by a pronounced change in the transcriptomic profile of the leg skeletal muscles, which is conservative in nature. In Hsp70– flies, the median lifespan was shorter and the locomotion speed was significantly lower compare to the control; at the same time, complex changes in the age-related dynamics of the skeletal muscle transcriptome were observed. Mass spectrometry-based quantitative proteomic showed that 47-day-old Hsp70– flies, compared with w1118, demonstrated multidirectional changes in the content of key enzymes of glucose metabolism and fat oxidation (glycolysis, pentose phosphate pathway, Krebs cycle, beta-oxidation and oxidative phosphorylation). Such dysregulation may be associated with a compensatory increase in the expression of other genes encoding chaperones (small Hsp, Hsp40, 60, and 70), which regulate specific sets of target proteins. Taken together, our data show that knockout of six Hsp70 genes slightly reduces the median lifespan of flies, but significantly reduces the locomotion speed, which may be associated with complex changes in the transcriptome of the leg skeletal muscles and with multidirectional changes in the content of key enzymes of energy metabolism.

Heat hardening enhances the energy metabolism activity and oxidative defense ability of Manila clam Ruditapes philippinarum under different thermal stress

Heat-hardening treatment can improve the thermal tolerance of aquatic organisms, likely due to enhanced antioxidant capacity and energy metabolism. In this study, the Heat-hardened Manila clam exhibited an increase in survival rate ranging from 15.5% to 80% compared to Non-hardened Manila clam under acute heat stress. Under chronic heat stress, following sub-lethal heat shock treatment, the activities of antioxidant enzymes-Catalase (CAT), Glutathione peroxidase (GSH-PX), Superoxide dismutase (SOD) in Heat-hardened Manila clam was significantly elevated in comparison to the control group (P < 0.05). Compared with the non-hardened Manila clam, the activity of energy metabolism enzymes - Na+/K+-ATPase (NKA), Ca2+/Mg2+-ATPase (CMA) of heat-hardened Manila clam decreased after the first sublethal heat shock treatment, and increased during recovery treatment, and the total ATPase activity significantly increased. Within 7 days of chronic heat stress, the activities of CAT and SOD in the Heat-hardened group higher than that in the non-hardened group. The balance between antioxidant ability and energy metabolism may be critical for the enhanced thermal tolerance observed in the Heat-hardened Manila clam. These findings indicated that Heat-hardening treatment is likely to enhance the resistance of Manila clam to high temperature in the natural environment. Such insights could be advantageous in aquaculture to protect Manila clam from the detrimental effects of heat stress.

Broncho-obstructive syndrome and the enzymes of cellular energy metabolism after coronavirus infection

Broncho-obstructive syndrome (BOS) after coronavirus infection is characterized by long-term, dry and painful cough which is hard for treatment, significantly reducing the quality of life of the patients. The goal of the study: to investigate the specific features of clinical manifestations of BOS diagnosed for the first time in patients belonging to different age groups in post-COVID-19 period and to estimate the degree of mitochondrial dysfunction by the imbalance of the enzymes of cellular energy metabolism. Materials and methods. 298 patients with BOS (age 18–78) were observed continuously for 2 years. Standard clinical, biochemical and functional examination was carried out, Saint George`s Respiratory Questionnaire (SGRQ) was used. Mitochondrial dysfunction was determined by the ratio of levels of two enzymes, lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH), in peripheral blood lymphocytes. Statistical data processing was performed in STATISTICA 10.1 program package. Results. The duration and severity of BOS manifestations increased with age, they were the most prominent in the age group older than 60 y/o. Bronchial asthma was diagnosed for the first time in 85 patients, most of them belonging to the group 18–25 y/o. In all the patients with BOS, the SGRQ coeffitient was above 50, and comorbidity was established in 82.4% of the patients. The longest duration of BOS (49.4±3.5 days) was established in the group older than 60 y/o (n = 86). LDH/SDH ratio decreased from 6 to 4.8–5.2 a.u. in all the age groups. Such changes should be taken into account in the patients from young age groups. Conclusion. The revealed low values of LDH/SDH ratio have not been shown in the available literature earlier. These values demonstrate the development of secondary mitochondrial dysfunction in post-COVID-19 period in both younger and older age groups, particularly, in patients with more severe progression of BOS. Estimation of this parameter would allow to revealthe personified characteristics for each patients, which is important for quantifying the efficacy and duration of the required antioxidant therapy.

Impact of Intermittent Fasting and Dietary Restriction on Redox State, Energetic Metabolism, and Liver Injury in Common Bile Duct Ligation Model.

The aim of this work was to test whether we can treat cholestasis with dietary approaches applied after the onset of the disease. The effects of intermittent fasting and dietary restriction on liver damage caused by common bile duct ligation (BDL) in rats were studied, with particular attention paid to changes in the activity of enzymes of energy metabolism and antioxidant protection. Morphological changes in liver tissue and serum markers of liver damage were assessed in rats with BDL kept for one month on ad libitum diet, intermittent fasting, or 35% dietary restriction. We studied parameters of glucose metabolism (activity of glycolysis and gluconeogenesis enzymes), TCA cycle, and indicators of oxidative stress and redox status of the liver tissue. Dietary restriction resulted in an increase in gluconeogenesis activity, antioxidant capacity, and autophagy activation. When implemented after BDL, none of the dietary restriction protocols reduced the level of oxidative stress, detrimental morphological and biochemical alterations, or the fibrosis progression. Thus, under severe damage and oxidative stress developing in cholestasis, dietary restrictions are not hepatoprotective and can only be used in a pre-treatment mode.

Crystal structure and function analysis of 6-phosphogluconate dehydrogenase in Mycobacterium tuberculosis

6-phosphogluconate dehydrogenase (6PGDH) is an essential enzyme in energy metabolism and redox reactions, and represents a potential drug target for the development of therapies targeting trypanosomes, plasmodium, or other pathogens. Tuberculosis, caused by Mycobacterium tuberculosis, is a contagious disease that severely affects human health, with approximately one-third of the world's population infected. However, the protein structure, exact oligomeric state, and catalytic mechanism of 6PGDH in Mycobacterium tuberculosis (Mt6PGDH) have remained largely unknown. In this study, we successfully purified and determined the structure of Mt6PGDH, revealing its function as a tetramer in both solution and crystal states. Through structural comparisons, we clarified the tetramer formation mechanism and the oligomeric organization of short-chain 6PGDHs. Additionally, we identified key residues for coenzyme recognition and catalytic activity. This work not only deepens our understanding of the enzymatic function of Mt6PGDH but also lays a foundation for the development of drugs targeting this enzyme.

BIOCHEMICAL INDICATORS OF MILITARY BLOOD ON THE ISCHEMIC AND DENERVATION PROCESS IN MUSCLES AFTER A MINE-EXPLOSIVE INJURYS

The injuries received are accompanied by massive damage to the soft tissues of the limbs, main vessels and nerves, and the development of compartment syndrome. Violation of muscle function in the case of a limb injury can be both a consequence of denervation — as a result of damage to peripheral nerves, and ischemia with subsequent necrosis and fibrosis — as a result of direct or indirect damage to muscles, «tenotomy syndrome» — in case of traumatic damage to tendons and muscles yams, with the simultaneous combination of denervation and ischemia. Markers for assessing the state of muscle tissue — levels of Na+, K+ and Ca++ electrolytes, indicators of kidney function (urea, creatinine); glucose and the products of its transformations — lactate (lacticacid) and pyruvate (pyruvic acid) and, finally, muscle enzymes, namely creatine kinase (CK) and lactate dehydrogenase (LDH). Objective. To study the biochemical indicators of blood (activity of energy metabolism enzymes and electrolyte content) of military personnel with ischemic contracture and muscle denervation after a mine-explosive injury. Methods. The blood serum of 45 people, who were divided into IV groups, was analyzed. The average age of patients of the II group was 33.75 ± 3.46; III — 37 ± 3.66; IV — 35.86 ± 2.35. The results. The activity of LDH and CK and the content of electrolytes Na+, K+, Ca++ were determined in blood serum. Conclusions. LDH plays a key role in lactate metabolism and maintenance of energy balance in skeletal muscle. Its increased activity indicates the presence of hypoxia due to ischemic contracture of the limb and damage to peripheral nerves. KK enzyme protects cell membranes from damage. The tendency to decrease the activity of CC is a negative sign that reflects the initial process of destruction of the cell membranes of muscles damaged by a mine-explosive injury. The obtained results can be used to determine the severity of pathological processes in patients after traumatic damage to peripheral nerves and ischemic contracture, as well as when assessing the expediency of surgical intervention.

S-nitrosoproteomics profiling elucidates the regulatory mechanism of S-nitrosylation on beef quality

This study aimed to quantitively profile the S-nitrosylation in beef semimembranosus (SM) with different treatments (nitric oxide donor or nitric oxide synthase inhibitor) by applying iodoTMT-based nitrosoproteomics. Results showed that 2096 S-nitrosylated cysteine sites in 368 proteins were detected in beef SM. Besides, differential SNO-modified proteins were screened, some of which were involved in crucial biochemical pathways, including calcium-releasing-related proteins, energy metabolic enzymes, myofibrils, and cytoskeletal proteins. GO analysis indicated that differential proteins were localized in a wide range of cellular compartments, such as cytoplasm, organelle, and mitochondrion, providing a prerequisite for S-nitrosylation exerting broad roles in post-mortem muscles. Furthermore, KEGG analysis validated that these proteins participated in the regulation of diverse post-mortem metabolic processes, especially glycolysis. To conclude, changes of S-nitrosylation levels in post-mortem muscles could impact the structure and function of crucial muscle proteins, which lead to different levels of muscle metabolism and ultimately affect beef quality.

Ceratophyllum demersum alleviates microplastics uptake and physiological stress responses in aquatic organisms, an overlooked ability

It has been demonstrated that microplastics (MPs) may be inadvertently ingested by aquatic animals, causing harm to their physiological functions and potentially entering the food chain, thereby posing risks to human food safety. To achieve an environmentally friendly and efficient reduction of MPs in freshwater environments, this experiment investigates the depuration effect of C. demersum on MPs using three common aquatic animals: Macrobrachium nipponense, Corbicula fluminea, and Bellamya aeruginosa as research subjects. The amounts of MPs, digestive enzyme activity, oxidative stress index, and energy metabolism enzyme activity in the digestive and non-digestive systems of three aquatic animals were measured on exposure days 1, 3, and 7 and on depuration days 1 and 3. The results indicated that the depuration effect of C. demersum and the species interaction were significant for the whole individual. Concerning digestive tissue, C. demersum was the most effective in purifying B. aeruginosa. When subjected to short-term exposure to MPs, C. demersum displayed a superior depuration effect. Among non-digestive tissues, C. demersum exhibited the earliest purifying effect on C. fluminea. Additionally, C. demersum alleviated physiological responses caused by MPs. In conclusion, this study underscores C. demersum as a promising new method for removing MPs from aquatic organisms.

Macrophage lysate-derived cytokine network combined with silk fibroin hydrogel promotes diabetic vascularized bone regeneration

Cell-based therapies are used extensively in tissue engineering because of their great biosafety and diverse biological functions. Among them, macrophage lysate provides a comprehensive and rich network of cytokines to modulate the local immune microenvironment. However, effective strategies for macrophage lysate-based biomaterials with immune-regulatory function are still lacking. In this study, we engineered a silk fibroin hydrogel loaded with THP-1 macrophage whole-cell lysate to regulate the local immune microenvironment and promote vascularized bone regeneration in diabetic bone defects. Specifically, by modulating the expression pattern of key enzyme in energy metabolism (mitochondrial phosphoenolpyruvate carboxykinase, PCK2) of THP-1 cells, we generated a whole-cell lysate enriched with anti-inflammatory factors. This whole-cell lysate facilitated osteogenic differentiation of BMSCs and angiogenesis of HUVECs in vitro, and incorporating this immunomodulatory whole-cell lysate into silk fibroin hydrogel enhanced vascularized bone regeneration in diabetes. Mechanistically, we revealed that PCK2 activated the nuclear factor-kappa B (NF-κB) signaling pathway in THP-1 macrophages by using proteomic profiling. This research provides new insights into the design of cell-derived biomaterials, aiming to improve the therapeutic outcomes of pathological bone defects.

Molecular Characterization of the Allergenic Arginine Kinase from the Edible Insect Hermetia illucens (Black Soldier Fly).

Arginine kinase (AK) is an important enzyme for energy metabolism of invertebrate cells by participating in the maintenance of constant levels of ATP. However, AK is also recognized as a major allergen in insects and crustaceans capable of cross-reactivity with sera of patients sensitized to orthologous proteins. In the perspective of introducing insects or their derivatives in the human diet in Western world, it is of primary importance to evaluate possible risks for allergic consumers. This work reports the identification and characterization of AK from Hermetia illucens commonly known as the black soldier fly, a promising insect for human consumption. To evaluate allergenicity of AK from H. illucens, putative linear and conformational epitopes are identified by bioinformatics analyses, and Dot-Blot assays are carried out by using sera of patients allergic to shrimp or mites to validate the cross-reactivity. Gastrointestinal digestion reduces significantly the linear epitopes resulting in lower allergenicity, while the secondary structure is altered at increasing temperatures supporting the possible loss or reduction of conformational epitopes. The results indicate that the possible allergenicity of AK should be taken in consideration when dealing with novel foods containing H. illucens or its derivatives.

Esters of Quinoxaline-7-Carboxylate 1,4-di-N-Oxide as Potential Inhibitors of Glycolytic Enzymes of Entamoeba histolytica: In silico Approach.

Esters of quinoxaline-7-carboxylate 1,4-di-N-oxide (7-carboxylate QdNOs) derivatives are compounds that inhibit the growth of Entamoeba histolytica</i>, the causative agent of amebiasis. Although these compounds cause changes in the redistribution of glycogen deposits within the parasite, it is unknown whether these compounds interact with enzymes of the glycolytic pathway. The aim of this study was to test the binding affinity of these compounds to pyrophosphate- dependent phosphofructokinase (PPi-PFK), triosephosphate isomerase (TIM), and pyruvate phosphate dikinase (PPDK) from E. histolytica</i> as a possible mechanism of action. The molecular docking study of the 7-carboxylate QdNOs derivatives and the proteins was performed using AutoDock/Vina software. Molecular dynamics simulation was performed for 100 ns. Among all the selected compounds, T-072 exhibited the best binding affinity to EhPPi- PFK and EhTIM proteins, while T-006 interacted best with EhPPDK. ADMET analysis revealed that T-072 was non-toxic, while T-006 could become harmful to the host. In addition, molecular dynamics showed that T-072 has stable interaction with EhPPi-PFK and EhTIM. Including all aspects, these data indicated that these compounds might inhibit the activity of key enzymes in energy metabolism leading to parasite death. Furthermore, these compounds may be a good starting point for the future development of new potent antiamebic agents.

Effects of host identity on the gut microbiota: A comparative study on three microtinae species.

Gut microbiota exert an immense effect on host health and host environmental adaptation. Furthermore, the composition and structure of gut microbiota are determined by the environment and host genetic factors. However, the relative contribution of the environment and host genetic factors toward shaping the structure of gut microbiota has been poorly understood. In this study, we characterized the fecal microbial communities of the closely related voles Neodon fuscus, Lasiopodomys brandtii, and L. mandarinus after caged feeding in the laboratory for 6 months, through high-throughput sequencing and bioinformatics analysis. The results of pairwise comparisons of N. fuscus vs. L. brandtii and L. mandarinus vs. L. brandtii revealed significant differences in bacterial diversity and composition after domestication. While 991 same operational taxonomic units (OTUs) were shared in three voles, there were 362, 291, and 303 species-specific OTUs in N. fuscus, L. brandtii, and L. mandarinus, respectively. The relative abundances of Proteobacteria and Prevotella, which are reported to be enriched in high-altitude populations, were significantly higher in high-altitude N. fuscus than in low-altitude L. brandtii after domestication. Firmicutes, which produce various digestive enzymes for energy metabolism, and Spirochaetes, which can degrade cellulose, were found in higher abundance in subterranean L. mandarinus than thatin L. brandtii which dwells on the earth surface. Our findings showed that some components of gut microbiota still maintained dominance even when different host species are reared under the same environmental conditions, suggesting that these bacteria are substantially influenced by host factors.

Effects of bleaching on oxygen dynamics and energy metabolism of two Caribbean coral species

As mass coral bleaching events become more frequent, it is increasingly important to elucidate the factors underlying coral susceptibility and survival. We measured photosynthesis, respiration, and O2 concentration at the coral tissue surface, Symbiodiniaceae genotypes, and energy metabolic enzyme activities in Agaricia agaricites and Orbicella franksi throughout experimentally-induced thermal bleaching (+3 °C). A. agaricites colonies started to bleach two days into the thermal treatment and were fully bleached between Days 19–31. In contrast, O. franksi colonies only started to bleach on Day 12 and five colonies fully bleached between Days 24–38 while the remining three colonies took up 55 days. Both species experienced decreased photosynthesis and respiration rates as bleaching progressed. As a result, daytime O2 concentration at the coral surface shifted from hyperoxia in unbleached corals to normoxia in partially bleached corals, and to near hypoxia in fully bleached corals. Additionally, nighttime tissue surface O2 concentration shifted from hypoxia to normoxia, likely resulting from decreased symbiotic algae density, respiration, and photosynthates that fuel coral aerobic respiration. Genetic profiling of internal transcribed spacer 2 (ITS2) revealed differences in Symbiodiniaceae clade proportions between control and bleached colonies. Activity levels of energy metabolic enzymes did not significantly vary between control and bleached A. agaricites, but malate dehydrogenase and strombine dehydrogenase activities were significantly higher in bleached O. franksi colonies compared to controls. These differences were driven by the three O. franksi colonies that took the longest to bleach and contained >98 % Durusdinium sp. D1. The shifts in O2 dynamics within the microhabitat of bleached corals may have important implications for the metabolism of the coral holobiont while the changes in Symbiodiniaceae ITS2 profile and the upregulation of energy metabolic enzymes identify a potential factor contributing to bleaching dynamics.

NASA SPRINT exercise program efficacy for vastus lateralis and soleus skeletal muscle health during 70 days of simulated microgravity.

The efficacy of the NASA SPRINT exercise countermeasures program for quadriceps (vastus lateralis) and triceps surae (soleus) skeletal muscle health was investigated during 70 days of simulated microgravity. Individuals completed 6° head-down-tilt bedrest (BR, n = 9), bedrest with resistance and aerobic exercise (BRE, n = 9), or bedrest with resistance and aerobic exercise and low-dose testosterone (BRE + T, n = 8). All groups were periodically tested for muscle (n = 9 times) and aerobic (n = 4 times) power during bedrest. In BR, surprisingly, the typical bedrest-induced decrements in vastus lateralis myofiber size and power were either blunted (myosin heavy chain, MHC I) or eliminated (MHC IIa), along with no change (P > 0.05) in %MHC distribution and blunted quadriceps atrophy. In BRE, MHC I (vastus lateralis and soleus) and IIa (vastus lateralis) contractile performance was maintained (P > 0.05) or increased (P < 0.05). Vastus lateralis hybrid fiber percentage was reduced (P < 0.05) and energy metabolism enzymes and capillarization were generally maintained (P > 0.05), while not all of these positive responses were observed in the soleus. Exercise offsets 100% of quadriceps and approximately two-thirds of soleus whole muscle mass loss. Testosterone (BRE + T) did not provide any benefit over exercise alone for either muscle and for some myocellular parameters appeared detrimental. In summary, the periodic testing likely provided a partial exercise countermeasure for the quadriceps in the bedrest group, which is a novel finding given the extremely low exercise dose. The SPRINT exercise program appears to be viable for the quadriceps; however, refinement is needed to completely protect triceps surae myocellular and whole muscle health for astronauts on long-duration spaceflights.NEW & NOTEWORTHY This study provides unique exercise countermeasures development information for astronauts on long-duration spaceflights. The NASA SPRINT program was protective for quadriceps myocellular and whole muscle health, whereas the triceps surae (soleus) was only partially protected as has been shown with other programs. The bedrest control group data may provide beneficial information for overall exercise dose and targeting fast-twitch muscle fibers. Other unique approaches for the triceps surae are needed to supplement existing exercise programs.

Knockout of Hsp70 Genes Modulates Age-Related Transcriptomic Changes in Leg Muscles and Reduces the Locomotion Speed and Lifespan of Drosophila melanogaster

This study investigated the effect of knockout of six Hsp70 genes (orthologues of the mammalian genes Hspa1a, Hspa1b, Hspa2, and Hspa8) on age-related changes in gene expression in the legs of Drosophila melanogaster, which contain predominantly skeletal muscle bundles. For this, the leg transcriptomic profile was examined in males of the w^(1118) control strain and the Hsp70^(-) strain on the 7th, 23rd and 47th days of life. In w^(1118) flies, an age-related decrease in the locomotion (climbing) speed (a marker of functional state and endurance) was accompanied by a pronounced change in the transcriptomic profile of the leg skeletal muscles, which is conservative in nature. In Hsp70^(-) flies, the median lifespan was shorter and the locomotion speed was significantly lower compared to the control; at the same time, complex changes in the age-related dynamics of the skeletal muscle transcriptome were observed. Mass spectrometry-based quantitative proteomics showed that 47-day-old Hsp70^(-) flies, compared with w^(1118) flies, demonstrated multidirectional changes in the contents of key enzymes of glucose metabolism and fat oxidation (glycolysis, pentose phosphate pathway, Krebs cycle, beta-oxidation, and oxidative phosphorylation). Such dysregulation may be associated with a compensatory increase in the expression of other genes encoding chaperones (small Hsp, Hsp40, 60, and 70), which regulate specific sets of target proteins. Taken together, our data show that knockout of six Hsp70 genes slightly reduced the median lifespan of flies, but significantly reduced the locomotion speed, which may be associated with complex changes in the transcriptome of the leg skeletal muscles and with multidirectional changes in the contents of key enzymes of energy metabolism.

ENHANCING GASTRIC ULCER MANAGEMENT: NOVEL INSIGHTS FROM TERAZOSIN-PANTOPRAZOLE COMBINATION THERAPY

In this present study, we explored a novel approach to gastric ulcer management by investigating the therapeutic potential of terazosin, an alpha-1 adrenergic receptor inhibitor, in combination with pantoprazole, a common anti-ulcer agent. Employing an ethanol-induced rat-gastric ulcer model, the study demonstrated that terazosin pre-treatment significantly reduced ulcer formation, with the terazosinpantoprazole combination exhibiting superior mucosal protection compared to pantoprazole alone. Histopathological analysis revealed preserved mucosal structure and reduced neutrophil infiltration, indicating an anti-inflammatory effect. At a molecular level, the combination treatment groups exhibited elevated levels of phosphoglycerate kinase 1 (PGK-1), a vital enzyme in cellular energy metabolism, while inflammatory markers IκB kinase (IKK) and interleukin- 6 (IL-6) were significantly reduced, signifying mitigation of inflammation. These findings of the three different combinations of terazosin with pantoprazole indicate that this can be a potential approach for the treatment of gastric ulcers and can help in reducing the existing pantoprazole dose.

Comparative physiological, biochemical and proteomic analyses reveal key proteins and crucial regulatory pathways related to drought stress tolerance in faba bean (Vicia faba L.) leaves

Drought is one of the important abiotic factors that affect faba bean growth and productivity in the Mediterranean region. In order to study the response of faba bean plant to water-deficit stress, a physiological and proteomic analysis was carried out in leaf tissue. All physiological parameters were affected by drought. The physiological mechanism underlying the response of faba bean leaves to water-deficit was therefore attributed to the alleviation of oxidative stress via the accumulation of proline and to the synergistic action of the antioxidant enzyme system (CAT, SOD, APX and GPOX). Proteomic analysis identified 2000 proteins from faba bean leaves, of which were 81 differentially expressed. Of those, 36 were downregulated and 45 were upregulated under water-deficit treatment. KEGG and GO enrichments indicated differentially abundant proteins (DAPs) related to photosynthesis, antioxidants and ROS detoxifying enzymes, biosynthesis of amino acids and secondary metabolites, molecular chaperones, signal transduction, energy and carbohydrate metabolism and metabolic enzymes. The current results provide evidence for a complex synergetic pathway, in which ROS detoxification mechanisms and photoprotection constituted the major aspect of water-deficit tolerance in faba bean leaves. These results offer a foundational basis regarding the molecular mechanism involved in drought resistance within the faba bean species.