Correlation of diabetic renal hypoperfusion with microvascular responses of the skeletal muscle: a rat model study using diffuse correlation spectroscopy.

Using diffuse correlation spectroscopy, we assessed the renal blood flow and thigh muscle microvascular responses in a rat model of type 2 diabetes. The blood flow index at the renal surface decreased significantly with arterial clamping, cardiac extirpation, and the progression of diabetic endothelial dysfunction. Renal blood flow measured in diabetic and nondiabetic rats also showed a significant correlation with the reactive hyperemic response of the thigh muscle. These results suggest shared microcirculatory dysfunction in the kidney and skeletal muscle and support endothelial responses in the skeletal muscle as a potential noninvasive biomarker of renal hypoperfusion.

Circulating microRNA Profiles Identify a Patient Subgroup with High Inflammation and Severe Symptoms in Schizophrenia Experiencing Acute Psychosis.

Schizophrenia is a complex and heterogenous psychiatric disorder. This study aimed to demonstrate the potential of circulating microRNAs (miRNAs) as a clinical biomarker to stratify schizophrenia patients and to enhance understandings of their heterogenous pathophysiology. We measured levels of 179 miRNA and 378 proteins in plasma samples of schizophrenia patients experiencing acute psychosis and obtained their Positive and Negative Syndrome Scale (PANSS) scores. The plasma miRNA profile revealed three subgroups of schizophrenia patients, where one subgroup tended to have higher scores of all the PANSS subscales compared to the other subgroups. The subgroup with high PANSS scores had four distinctively downregulated miRNAs, which enriched 'Immune Response' according to miRNA set enrichment analysis and were reported to negatively regulate IL-1ß, IL-6, and TNFα. The same subgroup had 22 distinctively upregulated proteins, which enriched 'Cytokine-cytokine receptor interaction' according to protein set enrichment analysis, and all the mapped proteins were pro-inflammatory cytokines. Hence, the subgroup is inferred to have comparatively high inflammation within schizophrenia. In conclusion, miRNAs are a potential biomarker that reflects both disease symptoms and molecular pathophysiology, and identify a patient subgroup with high inflammation. These findings provide insights for the precision medicinal strategies for anti-inflammatory treatments in the high-inflammation subgroup of schizophrenia.

Complete retroperitoneal cutaneous ureterostomy with robot-assisted radical cystectomy.

Introduction: Cutaneous ureterostomy is beneficial for older patients in a hypoalimentation state, providing less invasive options than intestinal tract reconstruction techniques. However, complications such as ileus and stoma site hernia still pose risks owing to the anatomical location of the ureter. We introduce a novel method, complete retroperitoneal cutaneous ureterostomy, performed simultaneously with robot-assisted radical cystectomy. Case presentation: Our technique involves extending the retroperitoneal space to minimize complications and achieve stent-free outcomes. The median procedure time for complete retroperitoneal cutaneous ureterostomy was approximately 30 min. The stent-free rates at 1 and 4 months postoperatively were 66.7% and 100%, respectively; no case of stent reinsertion after stent removal was reported. Conclusion: Our approach is promising for avoiding postoperative intestinal tract complications.

Clinical Efficacy and Openness to New Challenges of Low Dose Rate Brachytherapy for Prostate Cancer.

Over a century ago, low-dose-rate (LDR) brachytherapy was introduced to treat prostate cancer (PCa). Since then, it has been widely applied worldwide, including in East Asia. LDR brachytherapy has been performed in 88 institutes in Japan. Beneficial clinical outcomes of LDR brachytherapy for intermediate-to-high-risk PCa have been demonstrated in large clinical trials. These clinical outcomes were achieved through advances in methods, such as urological precise needle puncture and seed placement, and the quantitative decision making regarding radiological parameters by radiation oncologists. The combined use of LDR brachytherapy with other therapeutic modalities, such as external beam radiation and androgen deprivation therapy, for the clinical risk classification of PCa has led to better anticancer treatment efficacy. In this study, we summarized basic LDR brachytherapy findings that should remain unchanged and be passed down in urology departments. We also discussed the applications of LDR brachytherapy for PCa in various clinical settings, including focal and salvage therapies. In addition, we highlighted technologies associated with brachytherapy that are under development.

Efficacy and safety of the sodium-glucose co-transporter-2 inhibitor empagliflozin in elderly Japanese adults (≥65 years) with type 2 diabetes: A randomized, double-blind, placebo-controlled, 52-week clinical trial (EMPA-ELDERLY).

AIM: Use of sodium-glucose co-transporter-2 inhibitors (SGLT2is) for glycaemic control is increasing in individuals with type 2 diabetes (T2D) for their additional benefits on heart failure and chronic kidney disease. However, SGLT2is generally reduce body weight, which might promote sarcopenia in older individuals. We evaluated the effects of the SGLT2i empagliflozin on muscle mass and strength in addition to glucose control in elderly adults with T2D. MATERIALS AND METHODS: Individuals with T2D aged ≥65 years with body mass index ≥22 kg/m2 and glycated haemoglobin (HbA1c) 7.0%-10.0% were randomized 1:1 to once-daily empagliflozin 10 mg or placebo for 52 weeks. The primary endpoint was change from baseline in HbA1c at week 52. Secondary endpoints included changes from baseline in muscle mass and strength. RESULTS: Of the 129 individuals randomized, 72.4% were men, mean age 74.1 years, body mass index 25.6 kg/m2 and HbA1c 7.6%. The placebo-adjusted mean change from baseline in HbA1c at week 52 with empagliflozin was -0.57% [95% confidence interval (CI) -0.78, -0.36]. Change in body weight was -3.26 kg and -0.90 kg with empagliflozin and placebo, respectively (placebo-adjusted difference: -2.37 kg; 95% CI -3.07, -1.68). Placebo-adjusted change in muscle mass was -0.61 kg (95% CI -1.61, 0.39), fat mass -1.84 kg (95% CI -2.65, -1.04) and grip strength -0.3 kg (95% CI -1.1, 0.5). CONCLUSIONS: Empagliflozin improved glucose control and reduced body weight without compromising muscle mass or strength in elderly adults with T2D in this trial.

Pre-operative Plasma Fibrinogen Level as a Potential Predictor of Pathological T3 Upstaging in Clinically Localized Renal Cell Carcinoma.

BACKGROUND/AIM: We investigated pre-operative factors for predicting pathological T3 (pT3) upstaging in clinical T1 renal cell carcinoma (RCC). PATIENTS AND METHODS: We evaluated 181 patients with renal tumors suspected to be clinical T1 RCC. All patients had undergone a partial or radical nephrectomy. Pre-operative parameters, including patient characteristics, RENAL nephrometry score and blood tests were analyzed to determine factors predicting pT3 upstaging. RESULTS: Eight (4.4%) tumors were diagnosed as pT3. Large tumor diameter, less than 4 mm distance between the tumor and the renal collecting system and a high level of preoperative plasma fibrinogen were associated with pT3 stage. Multivariate analysis showed that a preoperative plasma fibrinogen level >330 mg/dl was a significant independent factor predicting upstage (p=0.041). Furthermore, among patients diagnosed with RCC (n=162), a preoperative plasma fibrinogen level >330 mg/dl was related to poor overall survival (p<0.001) and poor recurrence-free survival (p=0.002). CONCLUSION: A high preoperative plasma fibrinogen level may be a predictor of pT3 upstaging and may suggest the need for radical nephrectomy rather than partial nephrectomy because of the associated poor oncological outcomes.

Mechanism for exercise-mediated prevention against muscle wasting on extensor digitorum longus muscle in Spontaneously Diabetic Torii fatty rats.

We previously reported the significant increase in limb muscle strength and cross-sectional area of the type IIb muscle fibers in the extensor digitorum longus (EDL) muscle in a type 2 diabetic animal model, with Spontaneously Diabetic Torii (SDT) fatty rats (n = 6) undergoing regular treadmill exercise from 8 to 16 weeks of age compared with sedentary SDT fatty rats (n = 6). This study investigated the mechanism by which exercise training prevented skeletal muscle wasting in the EDL muscle of the SDT fatty rats. The endurance exercise for 8 weeks downregulated the expression of muscle RING-finger protein-1 (an E3 ubiquitin ligase) and upregulated the expression of CD31, insulin receptor substrate-2, and phosphorylated endothelial nitric oxide synthase in the EDL muscle of 16-week-old SDT fatty rats.Endurance exercise training might reduce muscle wasting by preventing muscle degradation and increasing the angiogenic response in the EDL muscle in type 2 diabetes.

Angiotensin II type 1a receptor deficiency alleviates muscle atrophy after denervation.

The study aim was to determine if suppressed activation of angiotensin II type 1 receptor (AT1) prevents severe muscle atrophy after denervation. The sciatic nerves in right and left inferior limbs were cut in AT1a knockout homo (AT1a-/-) male mice and wild-type (AT1a+/+) male mice. Muscle weight and cross-sectional areas of type IIb muscle fibers in gastrocnemius muscle decreased at 7 and 21 days postdenervation in both AT1a-/- mice and AT1a+/+ mice, and the reduction was significantly attenuated in the denervated muscles of AT1a-/- mice compared to the AT1a+/+ mice. Gene expressions in the protein degradation system [two E3 ubiquitin ligases (muscle RING-finger protein-1 and Atrogin-1)] upregulated at 7 days postdenervation in all denervated mice were significantly lower in AT1a-/- mice than in AT1a+/+ mice. Activations of nuclear factor κB and Forkhead box subgroup O1, and protein expression of monocyte chemoattractant protein-1 were significantly suppressed in the AT1a-/- mice compared with those in the AT1a+/+ mice. In addition, suppressed apoptosis, lower infiltration of M1 macrophages, and higher infiltration of M2 macrophages were significantly observed at 21 days postdenervation in the AT1a-/- mice compared with those in the AT1a+/+ mice. In conclusion, the AT1 receptor deficiency retarded muscle atrophy after denervation.

Dramatic response to pembrolizumab after pseudoprogression in a patient with advanced metastatic castration-resistant prostate cancer.

Introduction: Prostate cancer with a microsatellite instability-high or mismatch repair-deficient status is not common. Few reports of the response to pembrolizumab in metastatic castration-resistant prostate cancer in a real-world setting have been reported. This case report describes a dramatic response to pembrolizumab after initial pseudoprogression in a patient with microsatellite instability-high metastatic castration-resistant prostate cancer. Case presentation: A 70-year-old man was administered pembrolizumab for metastatic castration-resistant prostate cancer after the genetic evaluation of lymphadenectomy revealed a microsatellite instability-high status. His general condition dramatically improved after pseudoprogression. His favorable condition has been maintained for 1 year since the final dose. Conclusion: We experienced a case of dramatic response to pembrolizumab after pseudoprogression in a patient with advanced metastatic castration-resistant prostate cancer. In patients with metastatic castration-resistant prostate cancer and the microsatellite instability-high/mismatch repair-deficient phenotype, a few months follow-up is necessary to evaluate the efficacy of pembrolizumab.

Pre-operative Serum Albumin as a Potential Predictor of Benign Lesions in Renal Masses.

BACKGROUND/AIM: We investigated pre-operative factors for predicting whether renal masses are benign in order to facilitate the selection of optimal candidates for pre-operative biopsy. PATIENTS AND METHODS: We evaluated 278 patients with renal masses suspected to be clinically T1 or T2 renal cell carcinoma. All patients had undergone a partial or radical nephrectomy. Pre-operative parameters, including patient characteristics, tumor size, and blood tests, were utilized to predict which lesions were benign. RESULTS: Twenty-five lesions (9.0%) were benign. Multivariate analysis showed that female sex [odds ratio (OR)=2.92, p=0.016], serum albumin ≥4.3 g/dl (OR=3.50, p=0.013), and tumor size <23 mm (OR=3.96, p=0.002) were significant independent factors for benign renal masses. The incidence of benign lesions in cases with all three factors (female sex, higher serum albumin, and smaller tumor size) was 4 of 16 (25.0%), which was significantly higher (p=0.037) than that in all cases (25/278; 9.0%). CONCLUSION: Relatively high pre-operative serum albumin levels may be a predictor of benign lesions when associated with female sex and smaller tumor size.

Endurance Exercise Training-Attenuated Diabetic Kidney Disease with Muscle Weakness in Spontaneously Diabetic Torii Fatty Rats.

BACKGROUND: The aim of this study was to evaluate protective effects of endurance exercise training against diabetic kidney disease (DKD) with muscle weakness by using male spontaneously diabetic Torii (SDT) fatty rats as type 2 diabetic animal models with obesity, hypertension, and hyperlipidemia. METHODS: Eight-week-old SDT fatty rats (n = 12) and Sprague-Dawley (SD) rats (n = 10) were randomly divided into exercise (Ex; SDT-Ex: n = 6, SD-Ex: n = 5) and sedentary groups (SDT-Cont: n = 6, SD-Cont: n = 5), respectively. Each group underwent regular treadmill exercise 4 times a week from ages 8-16 weeks. RESULTS: The exercise attenuated hypertension and hyperlipidemia and prevented increases in renal parameter levels without affecting blood glucose levels. In the SDT fatty rats, it prevented induction of renal morphological abnormalities in the interstitium of the superficial and intermediate layers of the cortex. Downregulated expression of endothelial nitric oxide synthase in the glomerulus of the SDT fatty rats was significantly upregulated by the exercise. The exercise upregulated the renal expressions of both medium-chain acyl-CoA dehydrogenase and peroxisome proliferator-activated receptor γ coactivator-1α related to fatty acid metabolism. It increased muscle strength and both muscle weight and cross-sectional area of type IIb muscle fibers in the extensor digitorum longus muscle in the SDT fatty rats. CONCLUSION: Endurance exercise training in type 2 diabetes ameliorates DKD by improving endothelial abnormality and enhancing fatty acid metabolism in addition to attenuated hypertension, hyperlipidemia, and muscle weakness independently of blood glucose levels.

Effect of GLP-1 receptor agonist, liraglutide, on muscle in spontaneously diabetic torii fatty rats.

This study investigated the effect of liraglutide, a glucagon-like peptide-1 receptor agonist, on skeletal muscles in rats with type 2 diabetes. Male SDT fatty rats (8-week-old) were provided liraglutide, or insulin-hydralazine for 8 weeks; control SDT fatty rats and SD rats were administered a vehicle. At 16 weeks of age, muscle strength of limbs was significantly lower in all SDT fatty rats compared to SD rats. While cross-sectional areas of type IIb muscle fibers in extensor digitorum longus muscle were significantly lower in SDT fatty rats than in SD rats, those of type I muscle fibers in soleus were similar in all rats. In the soleus of SDT fatty rats, liraglutide led to greater citrate synthase activity and cytochrome c oxidase subunit 5 B protein expression, independently of blood glucose and blood pressure levels. Liraglutide may contribute to preservation of mitochondrial content on soleus muscle in type 2 diabetes.

Transcription factor signal transducer and activator of transcription 6 (STAT6) is an inhibitory factor for adult myogenesis.

BACKGROUND: The signal transducer and activator of transcription 6 (STAT6) transcription factor plays a vitally important role in immune cells, where it is activated mainly by interleukin-4 (IL-4). Because IL-4 is an essential cytokine for myotube formation, STAT6 might also be involved in myogenesis as part of IL-4 signaling. This study was conducted to elucidate the role of STAT6 in adult myogenesis in vitro and in vivo. METHODS: Myoblasts were isolated from male mice and were differentiated on a culture dish to evaluate the change in STAT6 during myotube formation. Then, the effects of STAT6 overexpression and inhibition on proliferation, differentiation, and fusion in those cells were studied. Additionally, to elucidate the myogenic role of STAT6 in vivo, muscle regeneration after injury was evaluated in STAT6 knockout mice. RESULTS: IL-4 can increase STAT6 phosphorylation, but STAT6 phosphorylation decreased during myotube formation in culture. STAT6 overexpression decreased, but STAT6 knockdown increased the differentiation index and the fusion index. Results indicate that STAT6 inhibited myogenin protein expression. Results of in vivo experiments show that STAT6 knockout mice exhibited better regeneration than wild-type mice 5 days after cardiotoxin-induced injury. It is particularly interesting that results obtained using cells from STAT6 knockout mice suggest that this STAT6 inhibitory action for myogenesis was not mediated by IL-4 but might instead be associated with p38 mitogen-activated protein kinase phosphorylation. However, STAT6 was not involved in the proliferation of myogenic cells in vitro and in vivo. CONCLUSION: Results suggest that STAT6 functions as an inhibitor of adult myogenesis. Moreover, results suggest that the IL-4-STAT6 signaling axis is unlikely to be responsible for myotube formation.

Renoprotective effect of GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease in spontaneously diabetic Torii fatty rats.

BACKGROUND: The aim of this study is to investigate the renoprotective effect of the GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease (DKD) using an animal model of type 2 diabetes with several metabolic disorders. METHODS: Male 8-week-old spontaneously diabetic Torii (SDT) fatty rats (n = 19) were randomly assigned to three groups. The liraglutide group (n = 6) was injected subcutaneously with liraglutide. Another treatment group (n = 6) received subcutaneous insulin against hyperglycemia and hydralazine against hypertension for matching blood glucose levels and blood pressure with the liraglutide group. The control groups of SDT fatty (n = 7) and non-diabetic Sprague-Dawley rats (n = 7) were injected only with a vehicle. RESULTS: The control group of SDT fatty rats exhibited hyperglycemia, obesity, hypertension, hyperlipidemia, glomerular sclerosis, and tubulointerstitial injury with high urinary albumin and L-FABP levels. Liraglutide treatment reduced body weight, food intake, blood glucose and blood pressure levels, as well as ameliorated renal pathologic findings with lower urinary albumin and L-FABP levels. Liraglutide increased expressions of phosphorylated (p)-eNOS and p-AMPK in glomeruli, downregulated renal expression of p-mTOR, and increased renal expressions of LC3B-II, suggesting activation of autophagy. However, these effects were not caused by the treatments with insulin and hydralazine, despite comparable levels of hyperglycemia and hypertension to those achieved with liraglutide treatment. CONCLUSIONS: Liraglutide may exert a renoprotective effect via prevention of glomerular endothelial abnormality and preservation of autophagy in early-phase DKD, independent of blood glucose, and blood pressure levels.

Endurance Runners with Intramyocellular Lipid Accumulation and High Insulin Sensitivity Have Enhanced Expression of Genes Related to Lipid Metabolism in Muscle.

CONTEXT: Endurance-trained athletes have high oxidative capacities, enhanced insulin sensitivities, and high intracellular lipid accumulation in muscle. These characteristics are likely due to altered gene expression levels in muscle. DESIGN AND SETTING: We compared intramyocellular lipid (IMCL), insulin sensitivity, and gene expression levels of the muscle in eight nonobese healthy men (control group) and seven male endurance athletes (athlete group). Their IMCL levels were measured by proton-magnetic resonance spectroscopy, and their insulin sensitivity was evaluated by glucose infusion rate (GIR) during a euglycemic-hyperinsulinemic clamp. Gene expression levels in the vastus lateralis were evaluated by quantitative RT-PCR (qRT-PCR) and microarray analysis. RESULTS: IMCL levels in the tibialis anterior muscle were approximately 2.5 times higher in the athlete group compared to the control group, while the IMCL levels in the soleus muscle and GIR were comparable. In the microarray hierarchical clustering analysis, gene expression patterns were not clearly divided into control and athlete groups. In a gene set enrichment analysis with Gene Ontology gene sets, "RESPONSE TO LIPID" was significantly upregulated in the athlete group compared with the control group. Indeed, qRT-PCR analysis revealed that, compared to the control group, the athlete group had 2-3 times higher expressions of proliferator-activated receptor gamma coactivator-1 alpha (PGC1A), adiponectin receptors (AdipoRs), and fatty acid transporters including fatty acid transporter-1, plasma membrane-associated fatty acid binding protein, and lipoprotein lipase. CONCLUSIONS: Endurance runners with higher IMCL levels have higher expression levels of genes related to lipid metabolism such as PGC1A, AdipoRs, and fatty acid transporters in muscle.

Ketogenic diet feeding improves aerobic metabolism property in extensor digitorum longus muscle of sedentary male rats.

Recent studies of the ketogenic diet, an extremely high-fat diet with extremely low carbohydrates, suggest that it changes the energy metabolism properties of skeletal muscle. However, ketogenic diet effects on muscle metabolic characteristics are diverse and sometimes countervailing. Furthermore, ketogenic diet effects on skeletal muscle performance are unknown. After male Wistar rats (8 weeks of age) were assigned randomly to a control group (CON) and a ketogenic diet group (KD), they were fed for 4 weeks respectively with a control diet (10% fat, 10% protein, 80% carbohydrate) and a ketogenic diet (90% fat, 10% protein, 0% carbohydrate). After the 4-week feeding period, the extensor digitorum longus (EDL) muscle was evaluated ex vivo for twitch force, tetanic force, and fatigue. We also analyzed the myosin heavy chain composition, protein expression of metabolic enzymes and regulatory factors, and citrate synthase activity. No significant difference was found between CON and KD in twitch or tetanic forces or muscle fatigue. However, the KD citrate synthase activity and the protein expression of Sema3A, citrate synthase, succinate dehydrogenase, cytochrome c oxidase subunit 4, and 3-hydroxyacyl-CoA dehydrogenase were significantly higher than those of CON. Moreover, a myosin heavy chain shift occurred from type IIb to IIx in KD. These results demonstrated that the 4-week ketogenic diet improves skeletal muscle aerobic capacity without obstructing muscle contractile function in sedentary male rats and suggest involvement of Sema3A in the myosin heavy chain shift of EDL muscle.

Stenting Using the Rendezvous Technique for Postoperative Ureteral Complications in Cancer Patients.

PURPOSE: This study aimed to retrospectively evaluate the safety and efficacy of ureteral stent placement using the rendezvous technique for the treatment of postoperative ureteral complications in cancer patients. MATERIALS AND METHODS: From January 2005 to April 2015, 19 patients (2 men and 17 women; median age, 59; range, 42-79 years old) with unilateral ureteral lesions (ureteral leakages in 6, strictures in 4, and both in 9) underwent ureteral stent placement using the rendezvous technique. Percutaneous nephrostomy was performed, and stent placement was attempted via antegrade and retrograde approaches. The technical success, procedure-related complications, and clinical success were retrospectively analyzed. RESULTS: The median follow-up period was 29.8 months (range, 0.3-116.5 months). The ureteral stent placement was successful in 17 out of 19 patients (89.5%). Double J ureteral stent was used in 6 patients, and straight catheter as an internal-external nephro-ureteral stent was used in 11 patients. The rendezvous technique was used in the retroperitoneal space and urinary tract in 6 and 11 patients, respectively. No major complications related to the rendezvous technique occurred. Finally, 4 patients achieved stent-free condition (21.1%), and periodic stent exchange was continued in 9 (47.4%). However, permanent external drainage and surgical reconstruction were needed in 4 (21.1%) and 2 (10.5%) patients, respectively. The final clinical success rate was 68.4% (13 out of 19 patients). CONCLUSION: Ureteral stent placement using the rendezvous technique for the treatment of postoperative ureteral complications in cancer patients is safe and may be alternative to permanent external drainage and invasive surgical reconstruction. LEVEL OF EVIDENCE: Level 4, Case series.

Relationship between Urinary Liver-Type Fatty Acid-Binding Protein (L-FABP) and Sarcopenia in Spontaneously Diabetic Torii Fatty Rats.

BACKGROUND: Type 2 diabetes (T2D) is a known risk factor for diabetic kidney disease (DKD) and sarcopenia in older patients. Because there may be an interaction between DKD and sarcopenia, the aim of the present study is to investigate the relationship between urinary levels of liver-type fatty acid-binding protein (L-FABP) and sarcopenia using a novel rat model of T2D. METHODS: Male spontaneously diabetic Torii (SDT) fatty rats (n = 5) at 16 weeks of age were used as an animal model of T2D. Age- and sex-matched Sprague-Dawley (SD) rats (n = 7) were used as controls. Urine samples were obtained from the rats, and muscle strength was evaluated with the use of the forelimb grip test at 16, 20, and 24 weeks of age. Serum, kidney, soleus, and extensor digitorum longus (EDL) muscle samples were collected at 24 weeks of age. Urinary L-FABP levels were measured using dedicated enzyme-linked immunosorbent assays. RESULTS: Increased urinary L-FABP levels, focal glomerular sclerosis, moderate interstitial inflammation and fibrosis, and accumulation of renal oxidative proteins were significantly observed in the SDT fatty rats, compared to the SD rats. Muscle weight, muscle strength, cross-sectional areas of both type I and type IIb muscle fibers, and increasing rate of muscle strength were significantly decreased in the SDT fatty rats compared to the SD rats at 24 weeks. Urinary L-FABP levels at 20 and 24 weeks were significantly negatively correlated with muscle strength. Urinary L-FABP levels at 16 weeks were significantly negatively correlated with the increasing rate of muscle strength. CONCLUSIONS: Urinary L-FABP reflects the degree of muscle strength and weight, as well as cross-sectional areas of muscle fibers. Although further clinical study is needed, urinary L-FABP may be useful to monitor the progression of sarcopenia and DKD in T2D patients.

Age-related decrease in muscle satellite cells is accompanied with diminished expression of early growth response 3 in mice.

Skeletal muscle regeneration is mostly dependent on muscle satellite cells. Proper muscle regeneration requires enough number of satellite cells. Recent studies have suggested that the number of satellite cells in skeletal muscle declines as we age, leading to the impairment of muscle regeneration in older population. Our earlier study demonstrated that zinc finger transcription factor early growth response 3 (Egr3) plays an important role for maintaining the number of myoblasts, suggesting that age-related decrease in muscle satellite cell should be associated with the expression levels of Egr3. The aim of this study was to investigate whether aging would alter the Egr3 expression in satellite cells. A couple groups of male C57BL/6J mice were examined in this study: young (3 Mo) and old (17 Mo). Immunohistochemical staining showed that the satellite cell number decreased in normal and injured muscles of old mice. In fluorescence-activated cell sorting-isolated muscle satellite cells from normal and injured muscles, the mRNA expression of Egr3 was significantly decreased with age regardless of injury. In harmony with these results, Pax7 mRNA levels also decreased in the satellite cells from old mice. Alternatively, inhibition of Egr3 expression by shRNA decreased Pax7 protein expression in cultured myoblasts. These results suggest that Egr3 is associated with the age-related decline of muscle satellite cells in older population. Also, Egr3 might be implicated in the regulation of Pax7. Therefore, the loss of Egr3 expression may elucidate attenuated MSCs function and muscle regeneration in older age.