Improved Energy Metabolism Research Articles

Molecular strategies of the pygmy grasshopper Eucriotettix oculatus adapting to long-term heavy metal pollution

To study the heavy metal accumulation and its impact on insect exterior and chromosome morphology, and reveal the molecular mechanism of insects adapting to long-term heavy metal compound pollution habitats, this study, in the Diaojiang river basin, which has been polluted by heavy metals(HMs) for nearly a thousand years, two Eucriotettix oculatus populations was collected from mining and non-mining areas. It was found that the contents of 7 heavy metals (As, Cd, Pb, Zn, Cu, Sn, Sb) in E. oculatus of the mining area were higher than that in the non-mining 1–11 times. The analysis of morphology shows that the external morphology, the hind wing type and the chromosomal morphology of E. oculatus are significant differences between the two populations. Based on the heavy metal accumulation，morphological change, and stable population density, it is inferred that the mining area population has been affected by heavy metals and has adapted to the environment of heavy metals pollution. Then, by analyzing the transcriptome of the two populations, it was found that the digestion, immunity, excretion, endocrine, nerve, circulation, reproductive and other systems and lysosomes, endoplasmic reticulum and other cell structure-related gene expression were suppressed. This shows that the functions of the above-mentioned related systems of E. oculatus are inhibited by heavy metal stress. However, it has also been found that through the significant up-regulation of genes related to the above system, such as ATP2B, pepsin A, ubiquitin, AQP1, ACOX, ATPeV0A, SEC61A, CANX, ALDH7A1, DLD, aceE, Hsp40, and catalase, etc., and the down-regulation of MAPK signalling pathway genes, can enhanced nutrient absorption, improve energy metabolism, repair damaged cells and degrade abnormal proteins, maintain the stability of cells and systems, and resist heavy metal damage so that E. oculatus can adapt to the environment of heavy metal pollution for a long time.

Investigating the Preventive Effects of Oral Consumption of Dactylorhiza Maculate (Salep) Hydro-alcoholic Extract on Appetite and Body Weight in Male Rats.

Obesity is the result of positive energy balance in which various hormones and neurotransmitters are involved. Using Dietary supplements is a common and popular method to lose weight. Medicinal plants with specific effects on metabolizing enzymes, blocking adipogenesis, and improving energy metabolism can be a suitable alternative to these supplements. In this study, the role of hydro-alcoholic extract of Dactylorhiza maculate (Salep) plant on obesity and its related hormones and antioxidants was investigated. Forty male Wistar rats were divided into five groups: Control, Sham, and Salep extract (three doses): 80, 160, and 320 mg/kg. The extract was fed by gavage for 29 days. After the 29th day, blood and tissue samples were taken. Rats' ELISA kits were used to measure adiponectin, obestatin, resistin, orexin-A, insulin, epinephrine, Agouti Related Neuropeptide (AgRP), omentin, chemerin, amylin, neuropeptide-Y (NPY), and ghrelin. In addition, we measured leptin, cholecystokinin (CCK), antioxidants, and lipid profile factors. Evaluation of weight changes showed that Salep extract helped the animals to lose weight significantly in the 160 and 320 mg/kg Salep groups. Leptin, adiponectin, AgRP, obestatin, CCK, chemerin, adiponectin, and total antioxidants displayed a significant increase compared to the control group. In contrast, ghrelin, omentin, resistin, NPY, amylin, orexin-A, epinephrine, and Malondialdehyde (MDA) decreased in the Salep groups. The lipid profile was also affected by the extract. These findings suggest that the Salep extract prevents appetite, reduces ghrelin, and affects digestive factors; the Salep extract can change the secretory factors of adipose tissue and lipid profile and ultimately help to lose weight.

Tetrahedral framework nucleic acids’ role in facilitating chronic diabetic wound repair via the endoplasmic reticulum-mitochondrial pathway

Under diabetic circumstances, keratinocytes are constantly exposed to hyperglycaemic micromilieu, leading to disrupted differentiation and increased chronic wound susceptibility during to sustained endoplasmic reticulum (ER) stress (ERS) and mitochondrial dysfunction during hyperglycaemia. As mitochondrial respiratory chain activity is a primary generator of intracellular reactive oxygen species (ROS), we postulated that tFNAs could potentially boost mitochondrial function and energy metabolism in the presence of oxidative stress. To this end, we first explored the ER-mitochondrial (ER-MITO) axis-associated intracellular transportation of tetrahedral framework nucleic acids (tFNAs). tFNAs are transported to the ER and mitochondria via caveolae-mediated endocytosis, thereby regulating the ER-MITO axis. Additionally, tFNAs reduce ERS by downregulating PERK-ATF 4-CHOP, thereby stabilising mitochondrial dynamics, improving energy metabolism, maintaining membrane potential polarisation, and scavenging generated reactive oxygen species to counteract oxidative stress during hyperglycaemia. Consequently, tFNAs restore cell proliferation, migration, and differentiation and enhance chronic wound healing and skin graft survival. Furthermore, tFNAs repaired the diabetic skin mechanical barrier, underscoring their versatility of ER-MITO axis modulation. Overall, this study highlights the importance of tFNAs in ER-MITO axis modulation and a novel therapeutic approach for chronic diabetic wound healing.

Clinical Characteristics of 118 Pediatric Patients With Acute Benign Myositis Associated With Influenza A Virus Infection.

The objective of this study was to investigate the clinical and laboratory features of acute benign myositis associated with influenza A virus infection in children. A retrospective analysis was performed on the clinical data of 118 children with acute benign myositis associated with influenza A virus infection who were admitted to the Children's Hospital of Chongqing Medical University during the epidemic period of influenza A from February 2023 to May 2023. (1) Most of the 118 children were preschool- or school-age. The most common symptom was sudden lower limb pain after fever, and bilateral calf myalgia was more common. The muscle enzyme spectrum ranged from 187.21 to 32191.00 μg/L (median: 3053 μg/L). Creatine kinase isoenzymes ranged from 5.15 to 749.7 μg/L (median 41.82 μg/L). Myoglobin ranged from 102.79 to 1200 μg/L (median 674.9 μg/L). (3) Examination: electromyography, muscle color Doppler ultrasound, radiograph and cardiac color Doppler ultrasound in Benign acute childhood myositis in children were rarely positive. (4) Treatment and prognosis: besides bed rest and a reduction of physical activity, oseltamivir treatment, drugs to improve energy metabolism, fluid replacement and alkalinization of symptomatic treatment. All children had a good prognosis without sequelae. This study summarized and analyzed the clinical characteristics of acute benign myositis associated with influenza A infection in children with the aim of allowing rapid and early diagnosis of the disease and reducing unnecessary diagnostic tests and treatments. Closely monitoring myalgia and the muscle enzyme spectrum is recommended to exclude other neuromuscular and metabolic diseases.

Chinmedomics strategy for elucidating the effects and effective constituents of Danggui Buxue Decoction in treating blood deficiency syndrome.

Danggui Buxue Decoction (DBD) is a clinically proven, effective, classical traditional Chinese medicine (TCM) formula for treating blood deficiency syndrome (BDS). However, its effects and effective constituents in the treatment of BDS remain unclear, limiting precise clinical therapy and quality control. This study aimed to accurately evaluate the effects of DBD and identify its effective constituents and quality markers. BDS was induced in rats by a combined injection of acetylphenylhydrazine and cyclophosphamide, and the efficacy of DBD against BDS was evaluated based on body weight, body temperature, energy metabolism, general status, visceral indices, histopathology, biochemical markers, and metabolomics. The effects of DBD on urinary and serum biomarkers of BDS were investigated, and the associated metabolic pathways were analyzed via metabolomics. Guided by Chinmedomics, the effective constituents and quality markers of DBD were identified by analyzing the dynamic links between metabolic biomarkers and effective constituents in vivo. DBD improved energy metabolism, restored peripheral blood and serum biochemical indices, and meliorated tissue damage in rats with BDS. Correlation analyses between biochemical indices and biomarkers showed that 15(S)-HPETE, LTB4, and taurine were core biomakers and that arachidonic acid, taurine, and hypotaurine metabolism were core metabolic pathways regulated by DBD. Calycosin-7-glucoside, coumarin, ferulic acid sulfate, cycloastragenol, (Z)-ligustilide + O, astragaloside IV, acetylastragaloside I, and linoleic acid were identified as effective constituents improving the hematopoietic function of the rats in the BDS model. Additionally, calycosin-7-glucoside, ferulic acid, ligustilide, and astragaloside IV were identified as quality markers of DBD. The hematopoietic function of DBD was confirmed through analysis of energy metabolism, biochemical markers, histopathology, and metabolomics. Moreover, by elucidating effective constituents of DBD in BDS treatment, quality markers were confirmed using a Chinmedomics strategy. These results strengthen the quality management of DBD and will facilitate drug innovation.

Rhodiola crenulata alleviates hypobaric hypoxia-induced brain injury by maintaining BBB integrity and balancing energy metabolism dysfunction

Background/Purpose: Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba (R. crenulate), a famous and characteristic Tibetan medicine, has been demonstrated to exert an outstanding brain protection role in the treatment of high-altitude hypoxia disease. However, the metabolic effects of R. crenulate on high-altitude hypoxic brain injury (HHBI) are still incompletely understood. Herein, the anti-hypoxic effect and associated mechanisms of R. crenulate were explored through both in vivo and in vitro experiments. Study design/MethodsThe mice model of HHBI was established using an animal hypobaric and hypoxic chamber. R. crenulate extract (RCE, 0.5, 1.0 and 2.0 g/kg) and salidroside (Sal, 25, 50 and 100 mg/kg) was given by gavage for 7 days. Pathological changes and neuronal apoptosis of mice hippocampus and cortex were evaluated using H&E and TUNEL staining, respectively. The effects of RCE and Sal on the permeability of blood brain barrier (BBB) were detected by Evans blue staining and NIR-II fluorescence imaging. Meanwhile, the ultrastructural BBB and cerebrovascular damages were observed using a transmission electron microscope (TEM). The levels of tight junction proteins Claudin-1, ZO-1 and occludin were detected by immunofluorescence. Additionally, the metabolites in mice serum and brain were determined using UHPLC-MS and MALDI-MSI analysis. The cell viability of Sal on hypoxic HT22 cells induced by CoCl2 was investigated by cell counting kit-8. The contents of LDH, MDA, SOD, GSH-PX and SDH were detected by using commercial biochemical kits. Meanwhile, intracellular ROS, Ca2+ and mitochondrial membrane potential were determined by corresponding specific labeled probes. The intracellular metabolites of HT22 cells were performed by the targeted metabolomics analysis of the Q300 kit. The cell apoptosis and necrosis were examined by YO-PRO-1/PI, Annexin V/PI and TUNEL staining. In addition, mitochondrial morphology was tested by Mito-tracker red with confocal microscopy and TEM. Real-time ATP production, oxygen consumption rate, and proton efflux rate were measured using a Seahorse analyzer. Subsequently, MCU, OPA1, p-Drp1ser616, p-AMPKα, p-AMPKβ and Sirt1 were determined by immunofluorescent and western blot analyses. ResultsThe results demonstrated that R. crenulate and Sal exert anti-hypoxic brain protection from inhibiting neuronal apoptosis, maintaining BBB integrity, increasing tight junction protein Claudin-1, ZO-1 and occludin and improving mitochondrial morphology and function. Mechanistically, R. crenulate and Sal alleviated HHBI by enhancing the tricarboxylic acid cycle to meet the demand of energy of brain. Additionally, experiments in vitro confirmed that Sal could ameliorate the apoptosis of HT22 cells, improve mitochondrial morphology and energy metabolism by enhancing mitochondrial respiration and glycolysis. Meanwhile, Sal-mediated MCU inhibited the activation of Drp1 and enhanced the expression of OPA1 to maintain mitochondrial homeostasis, as well as activation of AMPK and Sirt1 to enhance ATP production. ConclusionCollectively, the findings suggested that RCE and Sal may afford a protective intervention in HHBI through maintaining BBB integrity and improving energy metabolism via balancing MCU-mediated mitochondrial homeostasis by activating the AMPK/Sirt1 signaling pathway.

Coreopsis tinctoria improves energy metabolism in obese hyperglycemic mice

Coreopsis tinctoria (CT) improves energy metabolism. However, the role of CT in alleviating obesity-induced hyperglycemia by targeting the liver remains unknown. Therefore, this article aims to explore the mechanism by which CT improves energy metabolism and resists hyperglycemia. The water and ethanol extracts of CT were administered to high-fat diet-induced (HFD) obese C57BL/6J mice at a dose of 4 g/kg.bw (low-dose water extract, WL; low-dose ethanol extract, EL) or 10 g/kg.bw (high-dose water extract, WH; high-dose ethanol extract, EH). Mice that consumed a maintenance diet (LFD) were included as blank controls. Network pharmacology, liquid chromatography-mass spectrometry (LC-MS), L02 cell cultivation, and liver transcriptomics were used to examine the mechanism and functional components of CT against obesity-induced hyperglycemia. The results indicated that WL significantly (p < 0.05) alleviated glucose intolerance and insulin resistance in obesity-induced hyperglycemia. Kaempferol is the main active compound of CT, which demonstrated significant (p < 0.05) anti-hyperglycemic effects in obese mice and L02 cells. Finally, kaempferol significantly (p < 0.05; fold change >1.2) shifted the genes involved in carbon metabolism, glycolysis/gluconeogenesis, and the mitogen-activated protein kinase (MAPK) pathways toward the trend of LFD, indicating that it exerts an anti-hyperglycemic effect through these molecular mechanisms. Overall, oral intake of CT lowers blood glucose and improves insulin sensitivity in mice with obesity-induced hyperglycemia. Kaempferol is the primary functional component of CT.

Anti-fatigue effect of Lateolabrax japonicus peptides in mice and the underlying action mechanism via in vitro and in vivo assays

Fatigue is a common health issue in today's society worldwide. Finding anti-fatigue functional substances seems warranted to alleviate fatigue-related issues. The Lateolabrax japonicus peptides (LPH) obtained via enzymatic hydrolysis were identified being rich in Glu, Gly, and hydrophobic amino acids, which exhibited antioxidant properties. However, other biological functions of LPH have yet to be reported. This study main goal was to investigate the anti-fatigue effects of LPH via a fatigue mice model, and further to elucidate its underlying mechanism using in vivo assay. The results indicated that LPH exhibited strong antioxidant activity and stability in vitro. Meanwhile, LPH significantly extended the swimming time of mice, while also decreasing fatigue marker levels (LA, BUN, CK, and MDA) in serum concurrently by increased levels of antioxidant enzymes, blood glucose, and Na+-K+-ATPase. Histopathological examination revealed that LPH effectively improved tissue damage caused by fatigue. Mechanistically, LPH upregulated the gene and protein expression of Nrf2 and AMPK, indicating its regulatory role in Keap1/Nrf2 and AMPK/SIRT1/PGC-1α/NRF1 signaling pathways. Furthermore, the study demonstrated that LPH could modulate the abundance and balance of fatigue-related gut microbiota (Butyricimonas, Helicobacter, Monoglobus, and Turicibacter). In summary, these findings indicated that LPH exerted its anti-fatigue effect by improving energy metabolism and reducing oxidative stress, suggesting its potential as a promising functional anti-fatigue nutraceutical in food industry.

The Hepatokine Orosomucoid 2 Mediates Beneficial Metabolic Effects of Bile Acids.

Bile acids (BAs) are pleiotropic regulators of metabolism. Elevated levels of hepatic and circulating BAs improve energy metabolism in peripheral organs, but the precise mechanisms underlying the metabolic benefits and harm still need to be fully understood. In the present study, we identified orosomucoid 2 (ORM2) as a liver-secreted hormone (i.e., hepatokine) induced by BAs and investigated its role in BA-induced metabolic improvements in mouse models of dietinduced obesity. Contrary to our expectation, under a high-fat diet (HFD), our Orm2 knockout (Orm2-KO) exhibited a lean phenotype compared to C57BL/6J control, partly due to the increased energy expenditure. However, when challenged with HFD supplemented with cholic acid (HFDCA), Orm2-KO eliminated the anti-obesity effect of BAs, indicating that ORM2 governs BA-induced metabolic improvements. Moreover, hepatic ORM2 overexpression partially replicated BA effects by enhancing insulin sensitivity. Mechanistically, ORM2 suppressed IFNγ/STAT1 activities in inguinal WAT (iWAT) depots, forming the basis for anti-inflammatory effects of BAs and improving glucose homeostasis. In conclusion, our study provides new insights into the molecular mechanisms of BA-induced liver-adipose crosstalk through ORM2 induction.

Single-cell RNA sequencing reveals cellular dynamics and therapeutic effects of astragaloside IV in slow transit constipation.

The cellular characteristics of intestinal cells involved in the therapeutic effects of astragaloside IV (AS-IV) for treating slow transit constipation (STC) remain unclear. This study aimed to determine the dynamics of colon tissue cells in the STC model and investigate the effects of AS-IV treatment by single-cell RNA sequencing (scRNA-seq). STC mouse models were developed using loperamide, with subsequent treatment using AS-IV. Colon tissues and feces were collected for scRNA-seq and targeted short-chain fatty acid quantification. We integrated scRNA-seq data with network pharmacology to analyze the effect of AS-IV on constipation. AS-IV showed improvement in defecation for STC mice induced by loperamide. Notably, in STC mice, epithelial cells, T cells, B cells, and fibroblasts demonstrated alterations in cell proportions and aberrant functions, which AS-IV partially rectified. AS-IV has the potential to modulate the metabolic pathway of epithelial cells through its interaction with peroxisome proliferator-activated receptor gamma (PPARγ). AS-IV reinstated fecal butyrate levels and improved energy metabolism in epithelial cells. The proportion of naïve CD4+T cells is elevated in STC, and the differentiation of these cells into regulatory T cells (Treg) is regulated by B cells and fibroblasts through the interaction of ligand-receptor pairs. AS-IV treatment can partially alleviate this trend. The status of fibroblasts in STC undergoes alterations, and the FB_C4_Adamdec1 subset, associated with angiogenesis and the Wingless-related integration (Wnt) pathway, emerges. Our comprehensive analysis identifies perturbations of epithelial cells and tissue microenvironment cells in STC and elucidates mechanisms underlying the therapeutic efficacy of AS-IV.

The effect of vine tea (Ampelopsis grossedentata) extract on fatigue alleviation via improving muscle mass

Ethnopharmacological relevanceVine Tea (VT, Ampelopsis grossedentata), boasts a venerable tradition in China, with a recorded consumption history exceeding 1200 years. Predominantly utilized by ethnic groups in southwest China, this herbal tea is celebrated for its multifaceted therapeutic attributes. Traditionally, VT has been employed to alleviate heat and remove toxins, exhibit anti-inflammatory properties, soothe sore throats, lower blood pressure, and fortify bones and muscles. In the realm of functional foods derived from plant resources, VT has garnered attention for its potential in crafting anti-fatigue beverages or foods, attributed to its promising efficacy and minimal side effects. Currently, in accordance with the Food Safety Standards set forth by the Monitoring and Evaluation Department of the National Health and Family Planning Commission in China, VT serves as a raw material in various beverages. Aim of the studyVT has an anti-fatigue or similar effect in folk. However, the underlying molecular mechanisms contributing to VT's anti-fatigue effects remain elusive. This study endeavors to investigate the influence of Vine Tea Aqueous Extract (VTE) on fatigue mitigation and to elucidate its operative mechanisms, with the objective of developing VTE as a functional beverage. Materials and methodsThe preparation of VTE involved heat extraction and freeze-drying processes, followed by the identification of its metabolites using UPLC-QTOF-MS to ascertain the chemical composition of VTE. A fatigue model was established using a forced swimming test in mice. Potential molecular targets were identified through network pharmacology, transcriptome analysis, and molecular docking. Furthermore, RT-PCR and Western blot techniques were employed to assess mRNA and protein expressions related to the AMPK and FoxO pathways. ResultsVTE significantly prolonged the duration of swimming time in an exhaustive swimming test in a dose-dependent manner, while simultaneously reducing the concentrations of blood lactic acid (LA), lactate dehydrogenase (LDH), serum urea nitrogen (SUN), and creatine kinase (CK). Notably, the performance of the high-dose VTE group surpassed that of the well-recognized ginsenoside. VTE demonstrated a regulatory effect akin to ginsenoside on the AMPK energy metabolism pathway and induced downregulation in the expression of Gadd45α, Cdkn1a, FOXO1, and Fbxo32 genes, suggesting an enhancement in skeletal muscle mass. These findings indicate that VTE can improve energy metabolism and muscle mass concurrently. ConclusionsVTE exhibits significant anti-fatigue effects, and its mechanism is intricately linked to the modulation of the AMPK and FoxO pathways. Crucially, no caffeine or other addictive substances with known side effects were detected in VTE. Consequently, vine tea shows substantial promise as a natural resource for the development of anti-fatigue beverages within the food industry.

Adipose knockout of H-ferritin improves energy metabolism in mice

ObjectiveFerritin, the principal iron storage protein, is essential to iron homeostasis. How iron homeostasis affects the adipose tissue is not well understood. We investigated the role of ferritin heavy chain in adipocytes in energy metabolism. MethodsWe generated adipocyte-specific ferritin heavy chain (Fth, also known as Fth1) knockout mice, herein referred to as FthAKO. These mice were analyzed for iron homeostasis, oxidative stress, mitochondrial biogenesis and activity, adaptive thermogenesis, insulin sensitivity, and metabolic measurements. Mouse embryonic fibroblasts and primary mouse adipocytes were used for in vitro experiments. ResultsIn FthAKO mice, the adipose iron homeostasis was disrupted, accompanied by elevated expression of adipokines, dramatically induced heme oxygenase 1(Hmox1) expression, and a notable decrease in the mitochondrial ROS level. Cytosolic ROS elevation in the adipose tissue of FthAKO mice was very mild, and we only observed this in the brown adipose tissue (BAT) but not in the white adipose tissue (WAT). FthAKO mice presented an altered metabolic profile and showed increased insulin sensitivity, glucose tolerance, and improved adaptive thermogenesis. Interestingly, loss of ferritin resulted in enhanced mitochondrial respiration capacity and a preference for lipid metabolism. ConclusionsThese findings indicate that ferritin in adipocytes is indispensable to intracellular iron homeostasis and regulates systemic lipid and glucose metabolism.

Repurposing lansoprazole to alleviate metabolic syndrome via PHOSPHO1 inhibition

Drug repurposing offers an efficient approach to therapeutic development. In this study, our bioinformatic analysis first predicted an association between obesity and lansoprazole (LPZ), a commonly prescribed drug for gastrointestinal ulcers. We went on to show that LPZ treatment increased energy expenditure and alleviated the high-fat diet-induced obesity, insulin resistance, and hepatic steatosis in mice. Treatment with LPZ elicited thermogenic gene expression and mitochondrial respiration in primary adipocytes, and induced cold tolerance in cold-exposed mice, suggesting the activity of LPZ in promoting adipose thermogenesis and energy metabolism. Mechanistically, LPZ is an efficient inhibitor of adipose phosphocholine phosphatase 1 (PHOSPHO1) and produces metabolic benefits in a PHOSPHO1-dependent manner. Our results suggested that LPZ may stimulate adipose thermogenesis by inhibiting the conversion of 2-arachidonoylglycerol-lysophosphatidic acid (2-AG-LPA) to 2-arachidonoylglycerol (2-AG) and reduce the activity of the thermogenic-suppressive cannabinoid receptor signaling. In summary, we have uncovered a novel therapeutic indication and mechanism of LPZ in managing obesity and its related metabolic syndrome, and identified a potential metabolic basis by which LPZ improves energy metabolism.

Anti-platelet aggregation activities of different grades of Angelica sinensis and their therapeutic mechanisms in rats with blood deficiency: insights from metabolomics and lipidomics analyses.

In traditional Chinese medicine, the radix of Angelica sinensis (Oliv.) Diels (RAS) is mainly used to replenish and invigorate the blood circulation. This study investigated anti-platelet aggregation activities were used by New Zealand rabbits, and high-performance liquid chromatography data were obtained to determine the spectrum-effect relationship for different commercial grades of RAS. Plasma and urine metabolites were examined using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry-based metabolomics to elucidate the mechanisms underlying the role of these metabolites in a rat model of blood deficiency (BD). Plasma and spleen metabolites were additionally examined using ultra-performance liquid chromatography plus Q-Exactive tandem mass spectrometry-based lipidomics to clarify the mechanisms of RAS in treating BD. The third grade of RAS exhibited the best activity in replenishing and invigorating blood in vitro and in vivo. Ferulic acid, ligustilide, senkyunolide I, uridine, and guanine are quality markers of anti-platelet aggregation activity. Based on the metabolomics results, 19 potential biomarkers were screened in plasma, and 12 potential metabolites were detected in urine. In lipidomics analyses, 73 potential biomarkers were screened in plasma, and 112 potential biomarkers were screened in the spleen. RAS may restore lipid metabolism by regulating disorders of glycerophospholipid and sphingolipid metabolism, the tricarboxylic acid cycle, amino acid metabolism (thereby improving energy metabolism), and arachidonic acid metabolism (thereby promoting blood circulation). These results provide a deeper understanding of the effects of different grades of RAS and a scientific reference for the establishment of grading standards and for the clinical use of RAS.

Saengmaeksan, a traditional polyherbal formulation containing Panax ginseng, improves energy metabolism during exercise.

Saengmaeksan (SMS), a representative oriental medicine that contains Panax ginseng Meyer, Liriope muscari, and Schisandra chinensis (1:2:1), is used to improve body vitality and enhance physical activity. However, there is limited scientific evidence to validate the benefits of SMS. Here, we investigated the in vitro and in vivo regulatory effects of SMS and its constituents on energy metabolism and the underlying molecular mechanisms. For this, quantitative real-time polymerase chain reaction, 3D holotomographic microscopy, western blotting, and glucose uptake experiments using 18F-fluoro-2-deoxy-D-glucose (18F-FDG) were performed using L6 cells to investigate in vitro energy metabolism changes. In addition, 18F-fluorocholine (18F-FCH) and 18F-FDG positron emission tomography/computed tomography (PET/CT) analyses, immunohistochemistry, and respiratory gas analysis were performed in mice post-endurance exercise on a treadmill. In the energy metabolism of L6 cells, a significant reversal in glucose uptake was observed in the SMS-treated group, as opposed to an increase in uptake over time compared to the untreated control group. Furthermore, P. ginseng alone and SMS significantly decreased the volume of lipid droplets. SMS also regulated the phosphorylation of extracellular signal-regulated kinase (ERK), phosphorylation of p38, mitochondrial morphology, and the expression of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE/Ref-1) in H2O2-stimulated L6 cells. In addition, SMS treatment was found to regulate whole body and muscle energy metabolism in rats subjected to high-intensity exercise, as well as glucose and lipid metabolism in skeletal muscle. Therefore, SMS containing P. ginseng ameliorated imbalanced energy metabolism through oxidative stress-induced APE/Ref-1 expression. SMS may be a promising supplemental option for metabolic performance.

Cell Reprogramming Strategies for Treating Osteoarthritis and Intervertebral Disc Degeneration.

Osteoarthritis (OA) and intervertebral disc degeneration (IVDD) are the most common degenerative bone and joint diseases, posing a major threat to patients' physical and mental health due to the occurrence of chronic pain and disability. Within this context, the absence of efficacious therapies has led to a growing interest in regenerative medicine. In particular, as a method that can erase the memory of differentiation and re-endow cells with pluripotency, cell reprogramming technologies have ushered in a new era of personalized therapy, which not only show great potential for the treatment of degenerative osteoarthropathies but also promise to achieve tissue regenerative and repair. However, compared to other areas of research, reprogramming technologies to treat OA and IVDD are still in the preliminary stages and require further investigation. This paper briefly introduces the characteristics of cell reprogramming; summarizes the pathological mechanisms of reprogramming to improves energy metabolism, aging, inflammation, oxidative stress, and immune imbalance in OA and IVDD under the background of microenvironment and immunity; highlights the significant advantages of reprogramming-derived cells compared to embryonic stem cells and mesenchymal stem cells, based on these advances, providing important strategies for its development and clinical application in OA and IVDD.

Okulistyczne aspekty terapii inhibitorami kotransportera sodowo-glukozowego 2. (SGLT-2) – nową grupą leków hipoglikemizujących

Sodium glucose cotransporter 2 is the major protein responsible for glucose reabsorption in the kidneys. Its inhibitors – gliflozins – constitute a new group of hypoglycaemic drugs. The aim of the study is a literature review of ophthalmic aspects of diabetes therapy with the use of this newly introduced group of drugs. Literature data report the expression of the sodium glucose cotransporter 2 not only in the kidneys, but also in non-renal tissues, e.g. in the retina and the lens. Moreover, they indicate its participation in the pathogenesis of diabetic retinopathy. In turn, sodium glucose cotransporter 2 inhibitors, according to the available literature, reduce edema and reduce the loss of pericytes of the retina, and thus may prevent pathological changes occurring in the retina in the course of diabetic retinopathy. The results of clinical trials provide evidence of their effectiveness in the treatment of ocular complications of diabetes, i.e. in preventing the development of diabetic retinopathy, reducing diabetic macular edema, and even inhibiting cataract progression. In addition, the literature provides evidence suggesting a beneficial effect of this new group of hypoglycemic drugs on diabetic retinopathy beyond the control of concentration of blood glucose per se, such as 1. improved energy metabolism, reduction of hypoxia, anti-inflammatory and anti-oxidant effects in the retina by inducing mild ketonemia, 2. as well as a reduction of production of reactive oxygen species via the ERK/1/2/cPLA2/AA/ROS cell pathway. Due to the innovativeness of the topic, the number of literature data in its scope is limited. Therefore, it should be keep in mind that the conclusions may not be complete.

Myocardial infarction protective effect of xyloglucan on Drosophila melanogaster: A review

Myocardial infarction, more often known as cardiac arrest, occurs when the supply of blood to the heart’s coronary artery decreases or ceases, causing damage to the heart muscle. Xyloglucan is a plant polysaccharide. Xyloglucan has been proven in several studies utilizing model organisms to reduce the risk of coronary heart disease by avoiding post-occlusion phases inhibiting apoptosis and enhancing energy metabolism. Many studies utilize Drosophila melanogaster because its SRY-related HMG-box 5 (SOX5) gene encodes a SOX family transcription factor; the human SOX5 ortholog, Sox102F, is well conserved in Drosophila melanogaster. Suppressing Sox102F in flies resulted in significant heart dysfunction, structural defects, and a disturbance in notch signal transduction. This demonstrates that SOX5 serves an important functional part in the heart and that variations in SOX5 concentrations may contribute to the possibility of myocardial infarction. Xyloglucan activity is significant in myocardial infarction and may be lowered in the myocardium after H/R damage by stimulating Notch signaling, which may benefit myocardial survival, angiogenesis, and cardiac function. This review discusses the roles of the human SOX5 and Drosophila SOX102F genes, the notch signaling system, and how xyloglucan in tamarind seeds may defend against heart damage by preventing apoptosis along with improving energy metabolism.

Danlou tablet attenuates ischemic stroke injury and blood‒brain barrier damage by inhibiting ferroptosis

Ethnopharmacological relevanceDanlou tablet (DLT) is a traditional Chinese medicinal formulation known for replenishing Qi, promoting blood circulation, and resolving stasis. Its pharmacological actions primarily involve anti-inflammatory, antioxidant stress reduction, antiapoptotic, proangiogenic, and improved energy metabolism. DLT has been confirmed to have favorable therapeutic effects on ischemic stroke (IS). However, the underlying mechanism through which DLT affects IS-induced brain injury remains unknown. Aim of the studyThis study aims to investigate the effects and underlying mechanisms of danlou tablet on ischemic stroke based on network pharmacology and experimental verification. Materials and methodsUsing a transient middle cerebral artery occlusion (tMCAO) mouse model, the impact of DLT on the blood‒brain barrier (BBB) and brain injury in mice was assessed. Network pharmacology and bioinformatics analyses were utilized to explore the potential mechanisms of DLT in treating IS. Endothelial cells were cultured to observe the effects of DLT on vascular endothelial cells after oxygen-glucose deprivation/reperfusion, and these findings were validated in the brains of tMCAO mice. ResultsDLT alleviated oxidative stress and brain damage in tMCAO mice, mitigating BBB damage. A total of 185 potential targets through which DLT regulates IS were identified, including COX2, a known critical marker of ferroptosis, which identified as a key target. In vitro and in vivo experiments demonstrated that DLT significantly (p < 0.05) improved cell death and vascular barrier damage in IS, reducing intracellular oxidative stress and COX2 protein levels while increasing SLC7A11 and GPX4 protein levels. ConclusionsThis study demonstrated that DLT maintained BBB integrity and alleviated brain injury of tMCAO mice by inhibiting ferroptosis. The study partially unraveled the mechanism through which DLT functioned in treating IS and further clarified the pivotal active components of DLT, thereby providing a theoretical scientific basis for treating IS with DLT.

QiShenYiQi pills preserve endothelial barrier integrity to mitigate sepsis-induced acute lung injury by inhibiting ferroptosis

Ethnopharmacological relevanceThe QiShengYiQi pill (QSYQ) is a traditional Chinese medicinal formulation. The effectiveness and safety of QSYQ in treating respiratory system disorders have been confirmed. Its pharmacological actions include anti-inflammation, antioxidative stress, and improving energy metabolism. However, the mechanism of QSYQ in treating sepsis-induced acute lung injury (si-ALI) remains unclear. Aim of the studySi-ALI presents a clinical challenge with high incidence and mortality rates. This study aims to confirm the efficacy of QSYQ in si-ALI and to explore the potential mechanisms, providing a scientific foundation for its application and insights for optimizing treatment strategies and identifying potential active components. Materials and methodsThe impact of QSYQ on si-ALI was evaluated using the cecal ligation and puncture (CLP) experimental sepsis animal model. The effects of QSYQ on endothelial cells were observed through coculturing with LPS-stimulated macrophage-conditioned medium. Inflammatory cytokine levels, HE staining, Evans blue staining, lung wet/dry ratio, and cell count and protein content in bronchoalveolar lavage fluid were used to assess the degree of lung injury. Network pharmacology was utilized to investigate the potential mechanisms of QSYQ in treating si-ALI. Western blot and immunofluorescence analyses were used to evaluate barrier integrity and validate mechanistically relevant proteins. ResultsQSYQ reduced the inflammation and alleviated pulmonary vascular barrier damage in CLP mice (all P < 0.05). A total of 127 potential targets through which QSYQ regulates si-ALI were identified, predominantly enriched in the RAGE pathway. The results of protein-protein interaction analysis suggest that COX2, a well-established critical marker of ferroptosis, is among the key targets. In vitro and in vivo studies demonstrated that QSYQ mitigated ferroptosis and vascular barrier damage in sepsis (all P < 0.05), accompanied by a reduction in oxidative stress and the inhibition of the COX2 and RAGE (all P < 0.05). ConclusionsThis study demonstrated that QSYQ maintains pulmonary vascular barrier integrity by inhibiting ferroptosis in CLP mice. These findings partially elucidate the mechanism of QSYQ in si-ALI and further clarify the active components of QSYQ, thereby providing a scientific theoretical basis for treating si-ALI with QSYQ.