Serum prolactin levels were positively related to metabolic indexes and disorders in male obese patients.

PURPOSE: The role of prolactin (PRL) in glucolipid metabolism was inconsistent, and there were few studies on the metabolic role of PRL in obese patients. The study aims to explore association between PRL level and metabolic disorders in male obese patients. METHODS: A retrospective study was conducted. Eighty-nine male patients with obesity were included, and their clinical data were recorded. RESULTS: A total of 89 male obese patients were included in this study. Their average age was 24.5 ± 9.0 years and BMI was 42.8 ± 9.1 kg/m2. The average waist circumference and body fat percentage was 129.6 ± 19.6 cm and 42.9 ± 8.0%, respectively. The median prolactin levels were 10.0 ng/ml (range: 3.93-30.1 ng/ml). 79.0% (49/62) of these patients presented with NAFLD and 77.3% (68/88) of them was dyslipidemia. Further, serum prolactin level was positively correlated with BMI (r = 0.225, P = 0.034), body fat percentage (r = 0.326, P = 0.017), ALT (r = 0.273, P = 0.011) and AST (r = 0.245, P = 0.029). Compared with low PRL group (<10 ng/ml), the incidence of morbid obesity and NAFLD was higher in high PRL group (morbid obesity: 71.1% vs 45.5%, P = 0.018 and NAFLD: 91.2% vs 64.3%, P = 0.013). In addition, the risk of NAFLD and morbid obesity in high PRL group (>10 ng/ml) was higher than low PRL group (OR:5.187, 95%CI 1.194-22.544, P = 0.028 and OR: 4.375, 95% CI 1.595-11.994, P = 0.004). The increased risk of NAFLD and morbid obesity in the high PRL group still existed after adjusting for age and Testosterone. CONCLUSION: Serum prolactin levels were positively associated with deterioration of metabolic indexes in male obese patients, as well as NAFLD and morbid obesity.

Direct Monitoring of Li2 S2 Evolution and Its Influence on the Reversible Capacities of Lithium-Sulfur Batteries.

The polysulfide (PS) dissolution and low conductivity of lithium sulfides (Li2 S) are generally considered the main reasons for limiting the reversible capacity of the lithium-sulfur (Li-S) system. However, as the inevitable intermediate between PSs and Li2 S, lithium disulfide (Li2 S2 ) evolutions are always overlooked. Herein, Li2 S2 evolutions are monitored from the operando measurements on the pouch cell level. Results indicate that Li2 S2 undergoes slow electrochemical reduction and chemical disproportionation simultaneously during the discharging process, leading to further PS dissolution and Li2 S generation without capacity contribution. Compared with the fully oxidized Li2 S, Li2 S2 still residues at the end of the charging state. Therefore, instead of the considered Li2 S and PSs, slow electrochemical conversions and side chemical reactions of Li2 S2 are the determining factors in limiting the sulfur utilization, corresponding to the poor reversible capacity of Li-S batteries.

The Whole-transcriptome Landscape of Diabetes-related Sarcopenia Reveals the Specific Function of Novel lncRNA Gm20743.

While the exact mechanism remains unclear, type 2 diabetes mellitus increases the risk of sarcopenia which is characterized by decreased muscle mass, strength, and function. Whole-transcriptome RNA sequencing and informatics were performed on the diabetes-induced sarcopenia model of db/db mice. To determine the specific function of lncRNA Gm20743, the detection of Mito-Sox, reactive oxygen species, Ethynyl-2'-deoxyuridine, and myosin heavy chain was performed in overexpressed and knockdown-Gm20743 C2C12 cells. RNA-seq data and informatics revealed the key lncRNA-mRNA interactions and indicated a potential regulatory role of lncRNAs. We characterized three core candidate lncRNAs Gm20743, Gm35438, 1700047G03Rik, and their potential function. Furthermore, the results suggested lncRNA Gm20743 may be involved in regulating mitochondrial function, oxidative stress, cell proliferation, and myotube differentiation in skeletal muscle cells. These findings significantly improve our understanding of lncRNAs that may mediate muscle mass, strength, and function in diabetes and represent potential therapeutic targets for diabetes-induced sarcopenia.

The ameliorating effects of metformin on disarrangement ongoing in gastrocnemius muscle of sarcopenic and obese sarcopenic mice.

Sarcopenia and obese sarcopenia are increasingly prevalent chronic diseases with multifactorial pathogenesis, and no approved therapeutic drug to date. In the established sarcopenic mice models, muscle weakness, ectopic lipid deposition, and inflammatory responses in both serum and gastrocnemius muscle were observed, which were even deteriorated in obese sarcopenic models. With metformin intervention for 5 months, metformin exhibited benefits and restoring effects on gastrocnemius muscle of sarcopenic mice, but less effective on that of obese sarcopenic mice, as reflected in the increased percentage of muscle mass and enlarged fiber cross-sectional area, enhanced grip strength and exercise capacities, as well as the ameliorated ectopic lipid deposition and partially restored level of TNF-α, IL-1ß, IL-6, MCP-1 and IL-1α, which may be via the activation of phospho-AMPKα (Thr172). The significant up-regulated mRNA and protein level of lipolysis related proteins like hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) may contribute to the ameliorated ectopic lipid deposition with metformin intervention. The uptake of free fatty acid may be also inhibited in obese sarcopenic mice with metformin administration, as reflected in down-regulated mRNA and protein level of fatty acid transporter CD36. Furthermore, NF-κB signaling pathway was involved in the anti-inflammatory effect of metformin. These findings suggest that metformin treatment may be conducive to the prevention of age-related sarcopenia by regulating lipid metabolism in skeletal muscle, i.e. enhanced lipolysis and attenuated hyper-inflammatory responses, which may be AMPK-dependent processes. Moreover, high-fat diet would aggravate the damage to ageing in skeletal muscles and reduced their reactivity to metformin.

CHRNA1 induces sarcopenia through neuromuscular synaptic elimination.

Sarcopenia seriously affects the quality of life of the elderly, but its molecular mechanism is still unclear. Degeneration in muscle innervation is related to age-related movement disorders and muscle atrophy. The expression of CHRNA1 is increased in the skeletal muscle of the elderly, and in aging rodents. Therefore, we investigated whether CHRNA1 induces the occurrence and development of sarcopenia. Compared with the control group, local injection of AAV9-CHRNA1 into the hindlimb muscles decreased the percentage of muscle innervation. At the same time, the skeletal muscle mass decreased, as manifested by a decrease in the gastrocnemius mass index and the cross-sectional area of the muscle fibers. The function of skeletal muscle also decreased, which was manifested by decreases of compound muscle action potential and muscle contractility. Therefore, we concluded that upregulation of CHRNA1 can induce and aggravate sarcopenia.

Stable Solid Electrolyte Interphase In Situ Formed on Magnesium-Metal Anode by using a Perfluorinated Alkoxide-Based All-Magnesium Salt Electrolyte.

Passivation of the Mg anode surface in conventional electrolytes constitutes a critical issue for practical Mg batteries. In this work, a perfluorinated tert-butoxide magnesium salt, Mg(pftb)2 , is codissolved with MgCl2 in tetrahydrofuran (THF) to form an all-magnesium salt electrolyte. Raman spectroscopy and density function theory calculation confirm that [Mg2 Cl3 ·6THF]+ [Mg(pftb)3 ]- is the main electrochemically active species of the electrolyte. The proper lowest unoccupied molecular orbital energy level of the [Mg(pftb)3 ]- anion enables in situ formation of a stable solid electrolyte interphase (SEI) on Mg anodes. A detailed analysis of the SEI reveals that its stability originates from a dual-layered organic/inorganic hybrid structure. Mg//Cu and Mg//Mg cells using the electrolyte achieve a high Coulombic efficiency of 99.7% over 3000 cycles, and low overpotentials over ultralong-cycle lives of 8100, 3000, and 1500 h at current densities of 0.5, 1.0, and 2.0 mA cm-2 , respectively. The robust SEI layer, once formed on a Mg electrode, is also shown highly effective in suppressing side-reactions in a TFSI- -containing electrolyte. A high Coulombic efficiency of 99.5% over 800 cycles is also demonstrated for a Mg//Mo6 S8 full cell, showing great promise of the SEI forming electrolyte in future Mg batteries.

Lysyl oxidase-like 2 inhibitor rescues D-galactose-induced skeletal muscle fibrosis.

Aging-related sarcopenia is currently the most common sarcopenia. The main manifestations are skeletal muscle atrophy, replacement of muscle fibers with fat and fibrous tissue. Excessive fibrosis can impair muscle regeneration and function. Lysyl oxidase-like 2 (LOXL2) has previously been reported to be involved in the development of various tissue fibrosis. Here, we investigated the effects of LOXL2 inhibitor on D-galactose (D-gal)-induced skeletal muscle fibroblast cells and mice. Our molecular and physiological studies show that treatment with LOXL2 inhibitor can alleviate senescence, fibrosis, and increased production of reactive oxygen species in fibroblasts caused by D-gal. These effects are related to the inhibition of the TGF-ß1/p38 MAPK pathway. Furthermore, in vivo, mice treatment with LOXL2 inhibitor reduced D-gal-induced skeletal muscle fibrosis, partially enhanced skeletal muscle mass and strength and reduced redox balance disorder. Taken together, these data indicate the possibility of using LOXL2 inhibitors to prevent aging-related sarcopenia, especially with significant fibrosis.

Effect of Mg Cation Diffusion Coefficient on Mg Dendrite Formation.

Dendrite formation is an important issue for the metal anode-based battery system. The traditional perception that Mg metal anode does not grow dendrite during operation has been challenged recently. Herein, we investigate the Mg electrodeposition behavior in a 0.3 M all-phenyl-complex (APC) electrolyte and confirm that Mg dendrites are readily formed at high current densities. A semiquantitative model indicates that the Mg-ion concentration on the electrode surface, limited by the intrinsic diffusion coefficient of the Mg cation group, decreases with increasing current density, resulting in an extra concentration polarization. However, Mg deposition at the tip of a protrusion on the electrode surface is hardly affected by the concentration polarization, and thus dendrite growth is more prone to occur at the tips. We find that the addition of LiCl in conventional APC electrolytes can suppress the Mg dendrite formation, mainly as a result of the enhanced Mg cation diffusion coefficient due to the influence of the LiCl additive, rather than the less pronounced electrostatic shield effect provided by Li cations.

The Association of Thyroid Hormones with Coronary Atherosclerotic Severity in Euthyroid Patients.

The aim of the work was to explore the correlation between thyroid hormones and coronary atherosclerotic severity. This cross-sectional study included 340 euthyroid patients who underwent diagnostic coronary artery angiography (CAG). Gensini Score (GS) was applied to assess the severity of coronary atherosclerosis. Thyroid hormones and routine biochemical parameters were measured. The associations between thyroid hormones and coronary atherosclerosis severity were analyzed. Thyroid hormones levels or parameters were taken as both continuous variables and tertiles into analysis, and the lowest tertile was usually used as the reference (OR=1) for medium and highest tertiles. Free triiodothyronine (FT3) level was associated with GS≥22 (Median GS) in Model I adjusted for age and sex [Continuous: OR=0.46, 95% CI (0.23, 0.92), p=0.029; Tertile 3: OR=0.54, 95% CI (0.30, 0.97), p=0.038], and Model II adjusted for all known risk factors of coronary artery disease (CAD) [Continuous: OR=0.44, 95% CI (0.20, 0.95), p=0.036; Tertile 3: OR=0.49, 95% CI (0.25, 0.96), p=0.039]. Subjects with highest tertile of FT3 to free thyroxine (FT4) ratio (FT3/FT4 ratio) appeared to have the remarkably decreased risk of CAD in both Non-adjusted Model [OR=0.49, 95% CI (0.24, 0.98), p=0.044] and Model I [OR=0.45, 95% CI (0.22, 0.93), p=0.031]. Higher FT3 level within normal range was independently and negatively associated with severity of coronary atherosclerosis. Besides, FT3/FT4 ratio was remarkably correlated with the prevalence of CAD in euthyroid population.

The Negative Impacts of Acromegaly on Bone Microstructure Not Fully Reversible.

Purpose: This study aimed to evaluate the bone turnover markers and bone microarchitecture parameters derived from high-resolution peripheral quantitative computed tomography (HR-pQCT) in active and controlled acromegaly patients. Methods: This cross-sectional study involved 55 acromegaly patients from a tertiary hospital (23 males and 32 females, aged 45.0 ± 11.6 years). Firstly, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and markers for bone turnover were assessed. Next, we derived peripheral bone microstructure parameters and volumetric bone mineral density (vBMD) through HR-pQCT. These parameters were compared between acromegaly patients and 110 healthy controls, as well as between 27 active and 28 controlled acromegaly patients. Moreover, the relationship between GH/IGF-1 and bone microstructure parameters was analyzed through multiple linear regression. Results: As compared with healthy controls, acromegaly patients exhibited elevated cortical vBMD, reduced trabecular vBMD, and increased trabecular inhomogeneity in the distal radius and tibia. While controlled acromegaly patients had slower bone turnover, they did not necessarily have better bone microstructure relative to active patients in intergroup comparison. Nevertheless, multiple regression indicated that higher IGF-1 was associated with lower tibial stiffness and failure load. Additionally, males with higher IGF-1 typically had larger trabecular separation, lower trabecular number, and larger cortical pores in the radius. Moreover, patients with elevated GH typically had more porous cortical bone in the radius and fewer trabeculae in the tibia. However, the compromised bone strength in active patients was partially compensated by increased bone thickness. Furthermore, no significant linkage was observed between elevated GH/IGF-1 and the most important HR-pQCT parameters such as trabecular volumetric bone density. Conclusion: Acromegaly adversely affected bone quality, even in controlled patients. As the deterioration in bone microstructure due to prolonged GH/IGF-1 exposure was not fully reversible, clinicians should be aware of the bone fragility of acromegaly patients even after they had achieved biochemical remission.

Understanding mechanisms of shape memory function deterioration for nitinol alloy during non-equilibrium solidification by electron beam.

INTRODUCTION: As an important advanced functional material, the memory effect of nitinol shape memory alloy (SMA) is the focus of research. According to the current research, the memory function of the alloy decreases after welding, and there is no sufficient explanation for the phenomenon. OBJECTIVES: For the problem, this research is to explore the underlying causes of the decrease of shape memory function after welding by analyzing the microstructure and micro defects. METHODS: The vacuum electron beam welding tests of 1 mm thick Ni50Ti50 alloy plate was carried out to determine the appropriate welding process parameter. And the shape memory function of the welded joint was compared with that of the base metal to analyze the change of memory function. RESULTS: It was found that the shape memory function of the welded joint decreased significantly under different strain variables. And the phase transition temperature also changed. CONCLUSIONS: This was due to the micro stress field produced by non-equilibrium solidification in molten pool promoted the formation and propagation of dislocations, increasing the dislocation density in the martensite. Dislocations entangled with each other in the martensite, showing a grid-like distribution, which destroyed the integrity of martensite substructure. At the same time, the twin substructure of martensite was often accompanied by vacancies, dislocations, stacking faults, and a consequently large stress field formed between twin planes due to lattice distortion. Secondary twin was identified inside martensite under micro shear stress, where the martensite showed the bending state. The habitual relationship between martensite phase and parent phase was destroyed, resulting in the decrease of shape memory function.

Fibrinogen, fibrin degradation products and risk of sarcopenia.

BACKGROUND & AIMS: Increasing data suggests that chronic low-grade inflammation plays an important role on development of sarcopenia. The present study was designed to identify the association between fibrinogen, fibrin degradation products (FDP) and sarcopenia risk in hospitalized old patients. METHODS: A total of 437 patients were enrolled in this cross-sectional study (148 with sarcopenia and 289 without sarcopenia). Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Body composition, grip strength and gait speed were performed to participants. Fibrinogen, FDP levels were measured. Logistic regression analyses were carried out to assess the association between fibrinogen and sarcopenia, between FDP and sarcopenia, respectively. RESULTS: Compared to non-sarcopenic patients, fibrinogen and FDP levels were found to be higher in the sarcopenic group (3.07 g/L vs 2.79 g/L, 1.75 µg/mL vs 1.00 µg/mL, respectively, p < 0.05). Multiple linear regression analysis showed a significant negative association between fibrinogen and gait speed (ß: -0.164, p = 0.008), and muscle strength (ß: -0.231, p < 0.001). Multivariable logistic regression analysis showed that fibrinogen and FDP were independently associated with sarcopenia (odds ratio 1.32 [95% confidence interval 1.03, 1.70], p = 0.009; odds ratio 1.07 [95% confidence interval 1.01, 1.19], p = 0.049, respectively). ROC curve revealed that the cutoff values of fibrinogen and FDP to predict sarcopenia risk were 2.54 g/L and 1.15 µg/mL, respectively. CONCLUSIONS: In hospitalized old patients, serum fibrinogen and FDP levels are elevated in sarcopenia patients than those without sarcopenia. Fibrinogen and FDP are associated with sarcopenia in a concentration-dependent manner.

Identification and In Vitro Functional Verification of Two Novel Mutations of GHR Gene in the Chinese Children with Laron Syndrome.

Purpose: Laron syndrome (LS) is a severe growth disorder caused by GHR gene mutation or post-receptor pathways defect. The clinical features of these patients collected in our present study were summarized, GHR gene variants were investigated and further in vitro functional verification was carried out. Methods: Four patients with LS were collected, their clinical characteristics were summarized, genomic DNA was extracted, and GHR gene was amplified and sequenced. GHR wild type (GHR-WT) and mutant GHR expression plasmids were constructed, and transiently transfected into HepG2 cells and HEK293T cells to observe the subcellular distribution of the GHR protein by immunofluorescence and to determine the expression of GHR and its post-receptor signaling pathway changes by Western blotting. Results: All of the four patients were male, and the median height was -4.72 SDS. Four GHR gene variants including c.587A>C (p.Y196S), c.766C>T (p.Q256*), c.808A>G (p.I270V) and c.1707-1710del (p.E570Afs*30) were identified, and the latter two were novel mutations. The results of mutant GHR plasmids transfection experiments and immunofluorescence assay showed that the subcellular distribution of GHR-Q256* and GHR-E570Afs*30 mutant proteins in HepG2 and HEK293T cells presented with a unique ring-like pattern, gathering around the nucleus, while GHR-Y196S mutant protein was evenly distributed on HepG2 cell membrane similar to GHR-WT. The GHR protein levels of HepG2 cells transiently transfected with GHR-Y196S, GHR-Q256* and GHR-E570Afs*30 were all significantly lower when compared with cells transfected with GHR-WT (P<0.05). Further mutant GHR post-receptor signal transduction investigation demonstrated that GH induced phosphorylated STAT5 levels of HepG2 cells transfected with three mutant plasmids were all significantly decreased in comparison with that of GHR-WT (P<0.05). Conclusions: Two novel GHR gene mutations (I270V and E570Afs*30) were found in our patients with LS. GHR mutations influenced the subcellular distribution and GHR protein levels, then led to the impaired post-receptor signal transduction, suggesting that the GHR mutations contributed to the pathological condition of LS patients.

Inhibition of soluble epoxide hydrolase (sEH) protects hippocampal neurons and reduces cognitive decline in type 2 diabetic mice.

Diabetes mellitus is a metabolic disorder that can lead to cognitive dysfunction. The hippocampus plays an important role in the cognitive function. Research has identified correlations between hippocampal impairment and diabetes, yet their intermediate remains unclear. Soluble epoxide hydrolase (sEH) is an enzyme that degrades epoxyeicosatrienoic acids (EETs), which have multiple protective effects by suppressing inflammation, apoptosis and oxidative stress. In this study, under diabetic conditions both hippocampal injury and cognitive decline are accompanied by upregulation of sEH. Moreover, the sEH inhibitor trans-4-[4-(3-adamantan-1-y1-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB) prevents cognitive dysfunction and decreased ROS accumulation and apoptosis in the diabetic hippocampus. t-AUCB treatment restored neuronal synaptic plasticity by restoring the expression of the postsynaptic proteins Postsynaptic density protein-95 (PSD95) and N-methyl-d-aspartate receptor subunit 2B (NR2B), the levels of which were positively correlated with Proline-rich tyrosine kinase 2 (Pyk2) levels under diabetic conditions. Thus, we suggest that hippocampal protection via sEH inhibition might be a potential therapeutic approach to attenuate the progression of cognitive decline in diabetes.

Correction to: Ghrelin ameliorates nerve growth factor Dysmetabolism and inflammation in STZ-induced diabetic rats.

In the original published article: A wrong GFAP immunohistochemistry staining image was inadvertently chosen to present as Control group image (the published Fig.1B).

Type 2 diabetes-induced overactivation of P300 contributes to skeletal muscle atrophy by inhibiting autophagic flux.

AIMS: Although autophagy impairment is a well-established cause of muscle atrophy and P300 has recently been identified as an important regulator of autophagy, the effects of P300 on autophagy and muscle atrophy in type 2 diabetes (T2D) remain unexplored. We aimed at characterizing the role of P300 in diabetic muscle and its underlying mechanism. MAIN METHODS: Protein levels of phosphorylated P300, total P300, acetylated histone H3, LC3, p62 and myosin heavy chain, and mRNA levels of Atrogin-1 and MuRF1 were analyzed in palmitic acid (PA)-treated myotubes and db/db mice. Autophagic flux was assessed using transmission electron microscopy, immunofluorescence and mRFP-GFP-LC3 lentivirus transfection in cells. Muscle weight, blood glucose and grip strength were measured in mice. Hematoxylin and eosin (H&E) staining was performed to determine changes in muscle fiber size. To investigate the effects of P300 on autophagy and myofiber remodeling, a P300 specific inhibitor, c646, was utilized. 3-Methyladenine (3-MA) was utilized to inhibit autophagosomes formation, and chloroquine (CQ) was used to block autophagic flux. KEY FINDINGS: Phosphorylation of P300 in response to PA enhanced its activity and subsequently suppressed autophagic flux, leading to atrophy-related morphological and molecular changes in myotubes. Inhibition of P300 reestablished autophagic flux and ameliorated PA-induced myotubes atrophy. However, this effect was largely abolished by co-treatment with the autophagy inhibitor CQ. In vivo results demonstrated that inhibition of P300 partially rescued muscle wasting in db/db mice, accompanied with autophagy reactivation. SIGNIFICANCE: The findings revealed that T2D-induced overactivation of P300 contributes to muscle atrophy by blocking autophagic flux.

Sulforaphane protects against skeletal muscle dysfunction in spontaneous type 2 diabetic db/db mice.

AIMS: Skeletal muscle diseases have become to be the most common complication in patients with type 2 diabetic mellitus (T2DM). However, the effective therapies against skeletal muscle diseases are not yet available. Sulforaphane (SFN) is an organic isothiocyanate found in cruciferous plants. Our aim was to explore whether SFN could attenuate the skeletal muscle diseases in spontaneous type 2 diabetic db/db mice. MATERIALS AND METHODS: The db/m and littermate db/db mice were treated with SFN or dimethyl sulfoxide. The grip strength of mice was measured by a grasping forcing machine. The electron transmission microscopy was used to perform the skeletal muscle. The western blot was used to detect the nuclear factor E2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signal pathway related proteins, and inflammatory and apoptotic associated proteins. The mRNA levels of anti-inflammatory and anti-oxidative relative genes were detected by RT-QPCR. KEY FINDINGS: We found that SFN could significantly increase the grip strength of the db/db mice. The lean mass and gastrocnemius mass were increased in the db/db mice after administration with SFN. Additionally, the db/db mice restored the skeletal muscle fiber organization after SFN treatment. Mechanistically, SFN could activate the Nrf2/HO-1 signal pathway, and downregulate the expression of inflammatory and apoptotic associated proteins. Furthermore, SFN could also regulate the mRNA levels of anti-inflammatory and anti-oxidative related genes. SIGNIFICANCE: Our results demonstrated that SFN can protect against skeletal muscle diseases in db/db type 2 diabetic mice and provide a potential drug to prevent skeletal muscle dysfunction in T2DM patients.

[Expressions of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases 1 in skeletal muscles of aged rats with sarcopenia].

OBJECTIVE: To investigate the changes of skeletal muscle mass and strength and the expressions of matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinases-1 (TIMP-1) and collagen-1 in the skeletal muscle of aged rats with sarcopenia. METHODS: With 11 young (6-month-old) SD rats as control group, 18 aged (25-month-old) SD rats were divided into two groups (n=9) according to the relative lean mass determined dual X-ray absorptiometry (DXA), namely aged control group and aged sarcopenia group (the relative lean mass was 2SD higher in aged control than in aged sarcopenia group. The forelimb grip strength of the rats was measured using an electronic grip strength meter. The extracellular matrix (ECM) of the rat's gastrocnemius was observed with HE staining and sirius Red staining, and the protein expressions of collagen-1, MMP-1, and TIMP-1 in the muscular tissues were detected with Western blotting. RESULTS: Compared with the young rats, the aged control rats had significantly lower relative grip strength (P < 0.01) and increased expressions of collagen-1 and TIMP-1 (P < 0.05) and ECM content in the skeletal muscles, but the relative lean mass and MMP-1 protein expression were comparable between the two groups (P>0.05). Compared with the aged control rats, the aged sarcopenic rats had significantly lowered relative lean mass (P < 0.01) and MMP-1 expressions of (P < 0.05) and increased expressions of collagen-1 and TIMP-1 proteins and ECM content in the muscular tissues (P < 0.05) without significant changes in the relative grip strength (P>0.05). CONCLUSIONS: MMP-1/TIMP-1 imbalance in the skeletal muscle during aging affects ECM metabolism and leads to increased collagen fibers, which in turn affects the skeletal muscle mass and function and contribute to the onset of sarcopenia.

Soluble epoxide hydrolase inhibitor protects against blood-brain barrier dysfunction in a mouse model of type 2 diabetes via the AMPK/HO-1 pathway.

Diabetes mellitus is a metabolic disorder that can lead to blood-brain barrier (BBB) disruption and cognitive decline. However, the mechanisms of BBB breakdown in diabetes are still unclear. Soluble epoxide hydrolase (sEH) is an enzyme that degrades epoxyeicosatrienoic acids (EETs), which have multiple protective effects on vascular structure and functions. In the current study, we showed increased vascular permeability of the BBB, which was accompanied by upregulation of sEH and downregulation of 14,15-EET. Moreover, the sEH inhibitor t-AUCB restored diabetic BBB integrity in vivo, and 14,15-EET prevented ROS accumulation and MEC injury in vitro. t-AUCB or 14,15-EET treatment provoked AMPK/HO-1 activation under diabetic conditions in vivo and in vitro. Thus, we suggest that decreased EET degradation by sEH inhibition might be a potential therapeutic approach to attenuate the progression of BBB injury in diabetic mice via AMPK/HO-1 pathway activation.