Serum Creatine Kinase Research Articles

Betaine alleviates methomyl-triggered oxidative stress-mediated cardiopulmonary inflammation in rats through iNOS/Cox2 and Nrf2/HO1/Keap1 signaling pathway.

Methomyl (MET), a universally used insecticide, has many adverse effects on various organs in both humans and animals including the liver, kidneys, and heart. Betaine (BET), a natural antioxidant, has a protective role against many toxicants-induced cardiovascular disorders. The present study was designed to elucidate the molecular mechanistic way underlying the mitigating effect of BET against MET-induced cardiopulmonary injury and inflammation in rats. Four groups of rats were used and orally administered the consequent materials daily for 28 days: normal saline, BET (250 mg/kg bwt), MET (2 mg/kg bwt), MET + BET. Blood and tissue (heart & lungs) samples were collected to assess the oxidative stress markers, lipid profile, biochemical markers, microscopic appearance, and inflammatory gene regulations. The results proved that MET induced oxidant/antioxidant imbalance, elevation of serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels, and deterioration in lipid profile. The histopathological inspection showed severe myocardial necrosis and interstitial pneumonia along with bronchitis and alveolar damage. There was a marked increase in the intensity of cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNOS) immunostaining with marked upregulation of the transcriptase levels of keap-1gene and downregulation of nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) genes in both heart and lung tissues of MET group. Otherwise, the coadministration of BET with MET markedly alleviated the abovementioned toxicological parameters. We can conclude that BET was able to reduce the MET-induced oxidative stress-mediated cardiovascular injury and pulmonary inflammation by modulating Keap-1/Nrf-2 signaling pathway and inactivating Cox-2 and iNOS expression which therefore reduced further cellular damage and inflammatory response.

O-01 A CASE OF LANGERHANS CELL HISTIOCYTOSIS WITH INVOLVEMENT OF THE HYPOTHALAMUS, BONE, AND LIVER

Abstract Introduction Langerhans cell histiocytosis (LCH) is a neoplastic disorder characterized by the abnormal infiltration of Langerhans cells, affecting multiple systems. Here, we report a rare case of LCH with involvement of the hypothalamus, liver, and bone. Clinical Case A 36-year-old female patient presented to the psychiatry department with complaints of anxiety, including sudden behavioral changes, headaches, increased forgetfulness, hypersomnia, and excessive thirst excessive eating, and memory lapses that persisted for three months. A contrast-enhanced pituitary MRI taken revealed a lobulated mass lesion, measuring 15x9x17 mm, extending into the interpeduncular cistern and anteriorly toward the optic chiasm, with cystic necrotic areas located at the base of the third ventricle (Figure 1A). Laboratory examinations indicated panhypopituitarism and central diabetes insipidus. Abdominal ultrasound revealed a hypoechoic area in liver segment 8.PET-CT showed a region of intense metabolic activity in the posterior section of the left mastoid bone (SUVmax: 12.4). In addition, a 14-mm focal area with increased fluorodeoxyglucose uptake was observed in liver segment 8 (SUVmax: 8.4) (Figure 1B).The temporal MRI showed a mass lesion extending to the petrous apex, filling the mastoid cells on the left side, with signal characteristics similar to the hypothalamic lesion (Figure 1C).Biopsy was performed on identified lesions. Both biopsy results were consistent with LCH. She was planned to administer two courses of cladribine therapy. Follow-up PET-CT after chemotherapy indicated that the liver and mastoid bone involvement had resolved. However, the patient’s neuropsychiatric symptoms did not improve following chemotherapy. Paraneoplastic autoimmune encephalitis was primarily suspected, and antibody testing was performed. Due to the progressive nature of the patient’s condition, intravenous immunoglobulin therapy was administered. On the fourth day of this treatment, the patient experienced increased agitation and delusions, and developed disorientation.50 mg of quetiapine was prescribed. Three days after starting quetiapine, the patient developed fever, tachypnea, muscle rigidity, increased confusion, and an acute increase in serum creatine kinase levels (29,000 U/L). The condition was evaluated as a neuroleptic malignant syndrome leading to the discontinuation of quetiapine. The patient was transferred to the intensive care unit (ICU).On the first day of ICU admission, the patient was intubated. Despite cardiac support, the patient died on the third day of ICU admission. Conclusion LCH is a rare but multisystemic inflammatory neoplasm. The absence of specific clinical features can lead to delays in diagnosis. Although LCH most commonly presents with bone and skin lesions, a multidisciplinary approach is crucial for an accurate diagnosis. Albeit rare, LCH should be considered in the differential diagnosis of patients presenting with hypothalamic masses.Figure 1:Magnetic resonance image of the hypothalamic mass (A), Magnetic resonance images revealing a mass lesion in the left mastoid bone (B) and a subcapsular lesion in liver segment 8 (C)

HC-A solution limb perfusion alleviates liver damage induced by limb ischemia-reperfusion injury in pigs.

The aim of the study was to explore a feasible method for alleviating limb ischemia-reperfusion injury (LI/RI) through the use of a high-concentration citrate solution (HC-A solution) for limb perfusion (LP). Eighteen pigs were divided into three groups: the Sham group, LI/RI group, and HCA group. The Sham group underwent exposure of the iliac artery and vein. The LI/RI group underwent tourniquet placement and clamping of the iliac artery and vein to simulate LI/RI. The HCA group received HC-A solution LP for 30 min through the left iliac artery below the level of blood flow occlusion based on the LI/RI group. Oxidative stress markers and inflammatory response markers were compared among the three groups. Compared to the LI/RI group, the HCA group showed significantly lower levels of serum creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and significantly greater activities of serum superoxide dismutase (SOD) (p < 0.05). There were no significant differences in serum interleukin-6 (IL-6) or in muscle MDA, SOD, TNF-α, and IL-6 between the HCA group and the LI/RI group (p > 0.05). Compared to the LI/RI group, MDA, TNF-α, and IL-6 levels in the liver were significantly lower in the HCA group (p < 0.05), while SOD activities were not significantly different (p > 0.05). Histopathological examination revealed reduced skeletal muscle and liver damage in the HCA group compared to the LI/RI group. HC-A solution LP can alleviate liver damage caused by LI/RI in pigs.

Efficacy and compatibility mechanism of bear bile powder in Shexiang Tongxin dropping pills for acute myocardial infarction treatment

BackgroundBear bile powder (BBP), a unique animal-derived medicine with anti-inflammatory and antioxidant effects, is used in Shexiang Tongxin dropping pills (STDP), which is applied to treat cardiovascular diseases, including acute myocardial infarction (AMI). The efficacy and compatibility mechanisms of action of BBP in STDP against cardiovascular diseases remain unclear. This study aimed to investigate the compatibility effects of BBP in STDP in rats with AMI.MethodsWe investigated the compatibility effects of BBP in STDP in rats with AMI. Non-targeted metabonomics, 16S rRNA analysis, RNA sequencing, and network pharmacology were performed to explore the underlying mechanisms.ResultsThe combination of BBP and CF (STDP without BBP) significantly reduced AMI-induced infarction size, pathological alterations of cardiac tissues, and serum lactate dehydrogenase and creatine kinase levels in rats, compared with CF or BBP treatment alone. Gut microbiota and metabonomics results revealed that the combination treatment could upregulate the relative abundance of Lactobacillus and downregulate that of Helicobacter, Bilophila, and Butyricimonas, thereby rebalancing the gut microbiota dysbiosis induced by AMI. Consequently, the intestinal metabolite levels of oleoylcholine, glutamylalanine, isokobusone, and hemorphin-4 were altered. However, treatment with CF or BBP alone has a weaker effect on these bacteria. Additionally, the combination treatment induced a 62.34% gene reversion rate compared with 55.56% for BBP and 30.20% for CF treatment alone. Modulation of endothelin 1 and growth factor receptor-bound protein 2 was identified as a key synergistic mechanism underlying the anti-AMI effects of BBP in STDP.ConclusionThis research provides a scientific explanation of the compatibility of BBP in STDP. Our findings suggested that combination treatment with CF and BBP synergistically attenuates AMI by altering gene expression, gut microbiota, and intestinal metabolite profiles.Graphical

Treatment With Full-Spectrum Cannabidiol Oil Improved the Pathological Findings of Dystrophic Mutant Mice.

Duchenne muscular dystrophy (DMD) is caused by pathogenic variants in the DMD gene, making muscle fibers susceptible to contraction-induced membrane damage. Given the potential beneficial action of cannabidiol (CBD), we evaluated the invitro effect of full-spectrum CBD oil on the viability of dystrophic muscle fibers and the invivo effect on myopathy of the mdx mouse, a DMD model. In vitro, dystrophic cells from the mdx mouse were treated with full-spectrum CBD oil and assessed with cell viability and cytotoxic analyses. Invivo, fourteen-day-old mdx mice received 10 mg/kg/day of the full-spectrum CBD oil for 14 days. We analyzed creatine kinase (CK) levels, liver damage markers, and histopathology of the diaphragm (DIA) and quadriceps (QUA [myonecrotic fibers with positive IgG staining, regenerated fibers/central nuclei, the minimum Feret's diameter, the fibrosis area, the inflammatory area, the presence of macrophages, and NF-kappa B content]). In vitro treatment with full-spectrum CBD oil showed a dose-dependent cytotoxic effect; however, invivo 10 mg/kg treatment was safe and effectively improved DMD histopathological assessment parameters in DIA and QUA: reduction of central nuclei: 1.7% ± 2.0% versus 22.4% ± 5.3% and 11.1% ± 10.7% versus 32.3% ± 4.6%; reduction of IgG+ myofibers: 0.6% ± 0.7% versus 8.4% ± 1.6% and 0.9% ± 0.3% versus 7.5% ± 1.0%; increase in myofiber size: 85.2 ± 3.2 versus 64.3 ± 4.0 μm and 106.5 ± 8.6 versus 81.2 ± 4.8 μm; decrease in inflammatory area: 6.2% ± 2.7% versus 15.1% ± 2.6% and 5.3 ± 4.1 versus 17.3% ± 2.8%; reduced macrophage area: 0.05% ± 0.1% versus 10.8% ± 4.3% and 1.0% ± 0.7% versus 10.3% ± 4.9%; NF-κB levels: 0.6% ± 0.1% versus 1.7% ± 0.2% and 1.7% ± 0.1% versus 5.2% ± 2.1%; and fibrosis: 5.6% ± 1.8% versus 12.0% ± 3.7% and 1.3% ± 0.5% versus 4.7% ± 1.5%. It also reduced serum CK. Full-spectrum CBD oil may represent a promising new approach to treating DMD, but its potential toxicity must be considered.

Comprehensive analysis of GDF15 as a biomarker in primary mitochondrial myopathies.

Mitochondrial diseases are caused by defects in oxidative phosphorylation, with primary mitochondrial myopathies (PMM) being a subset where muscle involvement is predominant. PMM presents symptoms ranging from exercise intolerance to progressive muscle weakness, often involving ocular muscles, leading to ptosis and progressive external ophthalmoplegia (PEO). PMM can be due to variants in mitochondrial or nuclear DNA. Growth differentiation factor 15 (GDF15) has been identified as an accurate biomarker for mitochondrial dysfunction. This study evaluates the utility of GDF15 as a biomarker for monitoring PMM. This observational study involved 50 adult PMM patients. Clinical data were collected alongside functional motor outcomes measured by the Motor Research Council scale, 6-min walk test, North Star Ambulatory Assessment, and 100-m run test (100MRT). Biomarkers including serum lactate, creatine kinase (CK), creatinine, and plasma GDF15 were assessed. Patients exhibited diverse phenotypes, including exercise intolerance (8%), progressive myopathy (22%), isolated PEO (24%), and PEO plus (42%). Significant correlations were found among motor function tests, with 100MRT being particularly sensitive. Biomarker analysis showed elevated lactate in 32%, elevated CK in 54%, reduced creatinine in 76%, and elevated GDF15 in 86% of cases. GDF15 levels correlated with motor performance, lactate levels, and mtDNA mutation load in muscle. Creatinine levels were strongly linked to disease severity. This study underscores the heterogeneity of PMM and the importance of reliable biomarkers. GDF15 was consistently elevated across all PMM phenotypes and genotypes, correlating well with disease severity. Reduced creatinine also emerged as a potential prognostic marker.

Increased postictal creatine kinase in epilepsy patients

Excessive muscle activity during generalized convulsive seizures in epilepsy patients in some cases can cause significant changes in blood plasma biochemical parameters, increased level of a set of metabolites, particularly, serum creatine kinase, accompanied by azotemia, which leads to prominent diagnostic and therapeutic difficulties. It is necessary to monitor the creatine kinase concentration after seizures, especially in case of electrolyte disturbances. To correct elevated creatine kinase or myoglobin levels, infusion therapy, urine alkalinization along with diuretics administration should be performed.

Shenmai Injection Reduces Cardiomyocyte Apoptosis Induced by Doxorubicin through miR-30a/Bcl-2.

To explore the molecular mechanism of Shenmai Injection (SMI) against doxorubicin (DOX) induced cardiomyocyte apoptosis. A total of 40 specific pathogen-free (SPF) male Sprague Dawley (SD) male rats were divided into 5 groups based on the random number table, including the control group, the model group, miR-30a agomir group, SMI low-dose (SMI-L) group, and SMI high-dose (SMI-H) group, with 8 rats in each group. Except for the control group, the rats were injected weekly with DOX (2 mg/kg) in the tail vein for 4 weeks to induce myocardial injury, and were given different regimens of continuous intervention for 2 weeks. Cardiac function was detected by echocardiography and myocardial pathological changes were observed by Van Gieson (VG) staining. Myocardial injury serum markers, including creatine kinase (CK), lactate dehydrogenase (LDH), troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble ST2 (sST2), and growth differentiation factor-15 (GDF-15) were detected by enzyme linked immunosorbent assay (ELISA). Cardiomyocyte apoptosis was observed by terminal deoxynucleotidyl transferase-mediated biotinylated dUTP triphosphate nick end labeling (TUNEL) and transmission electron microscopy, and the expressions of target proteins and mRNA were detected by Western blot and quantitative real time polymerase chain reaction (qRT-RCR), respectively. The treatment with different doses of SMI reduced rat heart mass index and left ventricular mass index (P<0.05), significantly improved the left ventricular ejection fraction (P<0.05), decreased the levels of serum CK, LDH, cTnT, and NT-proBNP (P<0.05 or P<0.01), reduced the levels of serum sST2 and GDF-15 (P<0.05 or P<0.01), decreased the collagen volume fraction, reduced the expressions of rat myocardial type I and type III collagen (P<0.05 or P<0.01), and effectively alleviated myocardial fibrosis. And the study found that SMI promoted the expression levels of miR-30a and Bcl-2 in myocardium, and down-regulated the expression of Bax, which inhibited the activation of Caspase-3 and Caspase-9 (P<0.05 or P<0.01), and improved myocardial cell apoptosis. SMI can alleviate myocardial injury and apoptosis caused by DOX, and its mechanism possibly by promoting the targeted expression of myocardial Bcl-2 protein through miR-30a.

Asymptomatic HyperCKemia in the Pediatric Population: A Prospective Study Utilizing Next-Generation Sequencing and Ancillary Tests.

Persistent elevation of serum creatine kinase levels (hyperCKemia) as an isolated manifestation presents a diagnostic challenge. Genetic myopathies are frequently involved; however, studies using next-generation sequencing (NGS) in pediatric patients are lacking, and the significance of genetic aberrations remains poorly understood. This study, therefore, aimed to investigate the relevance of NGS and the support of contemporary diagnostic tools in the diagnosis of pediatric asymptomatic hyperCKemia. This was a prospective cohort study enrolling pediatric (0-18 years old) patients meeting the predefined criteria for asymptomatic/paucisymptomatic hyperCKemia, excluding DMD gene deletion/duplication, recruited from a referral center. NGS, muscle MRI, EMG, and muscle biopsies with immunolabeling and inflammatory markers were performed according to a prespecified protocol. Data analysis was performed using descriptive/univariate statistics and Bayesian logistic regression. The series comprised 65 patients (78% male). NGS diagnosis was achieved in 55% of the cohort, with 70% of the pathogenic variants involving 7 genes (DMD, CAPN3, ANO5, DYSF, RYR1, GAA, and CAV3). The diagnostic rate was similar across all age groups; however, the gene profiles varied between the childhood and juvenile groups. EMG yielded myopathic features in 48% of the investigated cases, being predictive for diagnosis (p < 0.05; odds ratio [OR] 13.484, 95% CI 1.358-705.297). MRI showed normal (64%), focal fatty change (26%), or short-tau inversion recovery hyperintensity (10%) profiles, which were not predictive of diagnosis but supported muscle biopsy indications. Muscle biopsy provided a significant diagnostic effect (p < 0.05; OR 0.028, 95% CI 0.001-0.238), contributing to myopathologic features clarifying the variant pathogenicity and identifying inflammatory myopathies. The diagnoses remained inconclusive and unresolved in 14% and 29% of the cohorts, respectively. The diagnostic rate for patients with CK levels below the threshold of 3× was 42%. In multivariate analysis, NGS was the only variable achieving a significant diagnostic effect (β = 9.85, 95% CI 4.65-16.09). NGS, as the primary diagnostic tool for investigating hyperCKemia in the pediatric population, yielded a higher diagnostic rate. However, muscle biopsies are necessary to define variants of uncertain pathogenicity and aid in identifying inflammatory myopathies. EMG and MRI may play a role in hyperCKemia characterization, guiding the decision to perform muscle biopsy. The primary limitation of this study was that not all ancillary tests were performed in all recruited patients owing to ethical restrictions, which lowered the power of the predictive analysis.

Modified single-incision MIS-TLIF with expandable tubular assistance for degenerative lumbar spine diseases.

Evaluating the clinical value of the modified single-incision posterior median approach with expandable tubular assistance for lumbar interbody fusion in managing degenerative lumbar spine diseases. A retrospective analysis was conducted on 121 patients with single-level degenerative lumbar spine disease treated in our spine surgery department from January 2017 to December 2021. Of these, 72 patients underwent a modified single-incision posterior median approach with expandable tubular assistance lumbar interbody fusion (single-incision MIS-TLIF group), while 49 patients received the classic open posterior median incision P-TLIF (open surgery group). We collected basic demographic data including age, gender, BMI, and surgical level. Surgical-related indicators such as operation time, intraoperative blood loss, postoperative drainage, length of hospital stay, hospital costs, and complication rates were compared between the two groups. Laboratory results [whole blood C-reactive protein (CRP), serum creatine kinase (CK)] and clinical outcomes [VAS scores for low back and leg pain, Oswestry Disability Index (ODI), excellent and good rate according to the modified MacNab criteria, and interbody fusion rate according to the Brantigan criteria] were also evaluated. There were no significant differences in the basic demographics between the two groups. The operation time, postoperative hospital stay, and hospital costs were also similar between the groups. However, significant differences were observed in intraoperative blood loss, postoperative drainage, and complication rates. On postoperative days 1 and 3, whole blood CRP and CK levels showed marked differences between the groups. At 3, 6, and 12 months postoperatively, the single-incision MIS-TLIF group had lower ODI scores and VAS scores for back pain compared to the open surgery group. The excellent and good rate according to the MacNab criteria was higher in the single-incision MIS-TLIF group. There were no significant differences in leg pain VAS scores and interbody fusion rates at 12 months postoperatively between the groups. The modified single-incision posterior median approach with expandable tubular assistance lumbar interbody fusion is highly effective in treating degenerative lumbar spine diseases. It results in less postoperative pain, faster recovery, and significant improvement in postoperative functional outcomes, making it a valuable treatment option.

Antioxidant capacity and athletic condition of endurance horses undergoing nutraceutical supplementation.

Endurance is an equestrian discipline that primarily relies on aerobic metabolism. Intense aerobic exercise produces reactive oxygen species due to an imbalance between oxidant and antioxidant substances, known as oxidative stress, which may reduce athletic performance. This study evaluated the effects of a feed supplement containing natural antioxidants and omega-3 fatty acids on the blood antioxidant activity and the athletic condition of endurance horses undergoing an exercise test. Twelve Arabian endurance horses were randomly assigned to treatment or control groups. At T0, blood lactate, whole blood and red blood cells (RBC) antioxidant capacity were assessed. The horses performed an exercise test with heart rate monitoring. After 30 minutes, blood lactate, antioxidant capacity and serum creatine kinase (CK) were measured. The treatment group received the dietary supplement for 21 days, while controls maintained their diet. Then, the protocol was repeated (T1). Variables were compared within and between groups through two-way ANOVA and post-hoc tests. Significant time*group effects were observed for serum CK (p = 0.026), RBC antioxidant capacity at rest (p = 0.034) and post-exercise (p = 0.019). At T1, in treatment group, CK was lower than controls (p = 0.006), while RBC antioxidant capacity increased at rest (p = 0.037) and after exercise (p = 0.006) compared to T0. The dietary supplement showed efficacy in enhancing RBC antioxidant capacity, and it could be beneficial for horses engaged in intense aerobic exercise.

A polysaccharide from Glycyrrhiza uralensis attenuates myocardial fibrosis via modulating the MAPK/PI3K/AKT signaling pathway

Myocardial fibrosis (MF) is a key factor endangering public health worldwide. Glycyrrhiza uralensis polysaccharide (GPS) exhibits various biological activities. However, its activity against MF has not been reported. Herein, a neutral polysaccharide (GPS-1-1) was isolated from GPS through column chromatography, its structure was characterized and potential mechanism regarding anti-MF activity was evaluated. Notably, the molecular weight of GPS-1-1 was 14.073 kDa, and the monosaccharides consist of glucose, arabinose and galactose, with a → 4)-α-d-glucopyranose (Glcp)-(1 → and →4,6)-α-D-Glcp-(1 → backbone. Western blotting and immunofluorescence showed that GPS-1-1 inhibited the expression of fibrosis-related proteins, such as Collagen, Vimentin, Fibronectin and α-SMA in TGF-β1-induced fibrosis of cardiac fibroblasts (CFs), and inhibited the expression of TGF-β1-induced CFs migration ability and matrix metalloproteinases (MMP-2 and MMP-9), thus inhibiting the deposition of extracellular matrix in CFs. Additionally, in vivo analysis showed that GPS-1-1 reduced inflammatory cell infiltration and collagen deposition in cardiac tissues of mice with MF, and it inhibited the expression of serum lactate dehydrogenase, creatine kinase, and fibrosis-related factors. Combined transcriptomics, molecular docking and Western blotting analysis showed that platelet-derived growth factor subunit B (PDGFB) was involved in the anti-fibrosis process of GPS-1-1. Furthermore, qRT-PCR and Western blotting showed that GPS-1-1 inhibited the expression of MAPK/PI3K/AKT pathway related proteins, such as ERK, p-ERK, JNK, PI3K and p-PI3K in TGF-β1-induced CFs through PDGFB. Altogether, this study showed that GPS-1-1 inhibits the activation of the MAPK/PI3K/AKT pathway by down-regulating PDGFB expression to exert its anti-MF activity and its potential to be developed as a functional food and drug.

Urinary titin reflects the severity of walking ability, muscle strength, and muscle and cardiac damage in patients with Becker muscular dystrophy.

Becker muscular dystrophy (BMD) is a dystrophinopathy caused by a pathological variant of the DMD gene. Urinary titin, a degradation product of the giant protein titin present in muscle sarcomeres, has been used as a biomarker to reflect muscle degradation in Duchenne muscular dystrophy, a more severe dystrophinopathy. However, the clinical significance of urinary titin levels in BMD remains unclear. This study aimed to investigate the relationship between urinary titin levels and the clinical data in patients with BMD. Urine samples were collected from 123 patients with BMD, and urinary titin levels were measured. The association of urinary titin with clinical data, including age, physical measurements, physical activity, blood tests, and cardiopulmonary test results, was examined. A total of 257 urine samples were obtained from patients of 5-79years of age. The median urinary titin level was 72.6pmol/mg Cr (range 0.2-4325.0pmol/mg Cr). No strong correlation was found between urinary titin levels and age, physical measurements, physical function, blood test results, or cardiopulmonary function. However, on comparing clinical data between the age-matched high urinary titin (N=94) and normal (N=29) groups, the high urinary titin group had a significantly greater number of non-ambulatory cases (23.9% vs. 3.6%), weaker grip strength (16.3 vs. 32.0kg), and higher serum creatine kinase (1072 vs. 398 U/L) and cardiac troponin I (10.6 vs. 2.5pg/mL) levels. Urinary titin was identified as a biomarker reflecting walking ability, muscle strength, and skeletal and cardiac damage in patients with BMD.

Safety and Tolerability of Wharton's Jelly-Derived Mesenchymal Stem Cells for Patients With Duchenne Muscular Dystrophy: A Phase 1 Clinical Study.

This study was an open-label, dose-escalation, phase 1 clinical trial to determine the safety and dose of EN001 for patients with Duchenne muscular dystrophy (DMD). EN001, developed by ENCell, are allogeneic early-passage Wharton's jelly-derived mesenchymal stem cells that originate at the umbilical cord, with preclinical studies demonstrating their high therapeutic efficacy for DMD. This phase 1 clinical trial explored the safety and tolerability of EN001 as a potential treatment option for patients with DMD. Six pediatric participants with DMD were divided into two subgroups of equal size: low-dose EN001 (5.0×10⁵ cells/kg) and high-dose EN001 (2.5×10⁶ cells/kg). All participants were monitored for 12 weeks after EN001 administration to assess its safety. Dose-limiting toxicity (DLT) was evaluated across 2 weeks post administration. Exploratory efficacy was evaluated by measuring serum creatine kinase levels, and functional evaluations-including spirometry, myometry, the North Star Ambulatory Assessment, and the 6-minute walk test-were conducted at week 12 and compared with the baseline values. No participants experienced serious adverse events related to EN001 injection during the 12-week follow-up period. Mild adverse events included injection-related local erythema, edema, parosmia, and headache, but DLT was not observed. Functional evaluations at week 12 revealed no significant changes from baseline. These results demonstrated that EN001 are safe and well tolerated for patients with DMD, and did not cause serious adverse events. The efficacy of EN001 could be confirmed through larger-scale future studies that incorporate repeated dosing and have a randomized controlled trial design.

Profiling of Anti-Signal-Recognition Particle Antibodies and Clinical Characteristics in South Korean Patients With Immune-Mediated Necrotizing Myopathy.

This study evaluated the diagnostic utility of an anti-signal-recognition particle 54 (anti-SRP54) antibody-based enzyme-linked immunosorbent assay (ELISA) as well as the clinical, serological, and pathological characteristics of patients with SRP immune-mediated necrotizing myopathy (IMNM). We evaluated 87 patients with idiopathic inflammatory myopathy and 107 healthy participants between January 2002 and December 2023. The sensitivity and specificity of the ELISA for anti-SRP54 antibodies were assessed, and the clinical profiles of patients with anti-SRP54 antibodies were determined. The ELISA for anti-SRP54 antibodies had a sensitivity and specificity of 88% and 99%, respectively, along with a test-retest reliability of 0.92 (p<0.001). The 32 patients diagnosed with anti-SRP IMNM using a line-blot immunoassay included 28 (88%) who tested positive for anti-SRP54 antibodies using the ELISA, comprising 12 (43%) males and 16 (57%) females whose median ages at symptom onset and diagnosis were 43.0 years and 43.5 years, respectively. Symptoms included proximal muscle weakness in all 28 (100%) patients, neck weakness in 9 (32%), myalgia in 15 (54%), dysphagia in 5 (18%), dyspnea in 4 (14%), dysarthria in 2 (7%), interstitial lung disease in 2 (7%), and myocarditis in 2 (7%). The median serum creatine kinase (CK) level was 7,261 U/L (interquartile range: 5,086-10,007 U/L), and the median anti-SRP54 antibody level was 2.0 U/mL (interquartile range: 1.0-5.6 U/mL). The serum CK level was significantly higher in patients with coexisting anti-Ro-52 antibodies. This study has confirmed the reliability of the ELISA for anti-SRP54 antibodies and provided insights into the clinical, serological, and pathological characteristics of South Korean patients with anti-SRP IMNM.

The Effect of Protein Supplementation and Playing Time on Recovery Kinetics During a Congested Basketball Schedule.

Despite being widely promoted, protein supplementation's overall effectiveness during demanding basketball schedules remains unclear. This study investigated whether increased protein intake can accelerate recovery of muscle function during a 6-day congested basketball microcycle consisting of three consecutive games while accounting for the impact of playing time. In a randomized, two-trial, cross-over, double-blind repeated measures design, eighteen male basketball players were assigned to a high (High PT) or a moderate (Mod PT) playing time group and participated in two trials, receiving daily either milk protein (PRO trial) or an isoenergetic amount of carbohydrates. Each trial included three consecutive games (days 1-3) and a 72 h recovery period following Game 3 (days 4-6), during which players participated in low-load practice sessions. Isometric and isokinetic peak torque of knee extensors and flexors in the dominant limb, serum creatine kinase (CK) concentration, and erythrocyte glutathione (GSH) levels were assessed prior to each game and practice session. CK increased (p < 0.01) on game days in both groups but recovered earlier in Mod PT compared to High PT. Both eccentric and concentric peak torque was impaired (p < 0.01) up to 24-48 h post-G3 in a velocity-dependent manner. Eccentric peak torque of knee flexors at 60°/s declined to a greater extent in High PT compared to Mod PT (p < 0.01). Protein supplementation resulted in higher erythrocyte GSH concentration at pre-G2 (p < 0.05) and pre-G3 (p < 0.05) compared to placebo in both groups but did not affect any of the study outcomes. Increased protein intake during a congested basketball schedule increases erythrocyte GSH concentration but does not accelerate recovery of muscle function.

Inhibition of Mitochondrial Fission Protein Drp1 Ameliorates Myopathy in the D2-mdx Model of Duchenne Muscular Dystrophy.

Although current treatments for Duchenne Muscular Dystrophy (DMD) have proven to be effective in delaying myopathy, there remains a strong need to identify novel targets to develop additional therapies. Mitochondrial dysfunction is an early pathological feature of DMD. A fine balance of mitochondrial dynamics (fission and fusion) is crucial to maintain mitochondrial function and skeletal muscle health. Excessive activation of Dynamin-Related Protein 1 (Drp1)-mediated mitochondrial fission was reported in animal models of DMD. However, whether Drp1-mediated mitochondrial fission is a viable target for treating myopathy in DMD remains unknown. Here, we treated a D2-mdx model of DMD (9-10 weeks old) with Mdivi-1, a selective Drp1 inhibitor, every other day (i.p. injection) for 5 weeks. We demonstrated that Mdivi-1 effectively improved skeletal muscle strength and reduced serum creatine kinase concentration. Mdivi-1 treatment also effectively inhibited mitochondrial fission regulatory protein markers, Drp1(Ser616) phosphorylation and Fis1 in skeletal muscles from D2-mdx mice, which resulted in reduced content of damaged and fragmented mitochondria. Furthermore, Mdivi-1 treatment attenuated lipid peroxidation product, 4-HNE, in skeletal muscle from D2-mdx mice, which was inversely correlated with muscle grip strength. Finally, we revealed that Mdivi-1 treatment downregulated Alpha 1 Type I Collagen (Col1a1) protein expression, a marker of fibrosis, and Interleukin-6 (IL-6) mRNA expression, a marker of inflammation. In summary, these results demonstrate that inhibition of Drp1-mediated mitochondrial fission by Mdivi-1 is effective in improving muscle strength and alleviating muscle damage in D2-mdx mice. These improvements are associated with improved skeletal muscle mitochondrial integrity, leading to attenuated lipid peroxidation.

Duchenne Muscular Dystrophy: An Overview of Diagnosis, Management, and Pharmacological Treatment

Background: Duchenne muscular dystrophy (DMD) is a severe inherited neuromuscular disorder, primarily affecting males, characterized by progressive muscle weakness due to mutations in the dystrophin gene. This gene encodes dystrophin, a protein crucial for maintaining muscle cell integrity. DMD leads to the progressive loss of muscle function, cardiac complications, and intellectual disability. The disease typically results in wheelchair dependence by the early teens and early mortality due to respiratory or cardiac complications in the twenties. Aim: This overview aims to examine the diagnosis, management strategies, and pharmacological treatments for Duchenne muscular dystrophy. Methods: The article reviews current literature on the genetic basis, epidemiology, pathophysiology, and clinical manifestations of DMD. It also explores diagnostic methods including serum biomarkers, genetic testing, and muscle biopsy, as well as treatment options, particularly glucocorticoid therapy, and ongoing pharmacological interventions. Results: Early detection of elevated serum creatine kinase (CK) levels, along with genetic testing, is key to confirming DMD. Current pharmacological treatments primarily focus on corticosteroids to slow muscle degeneration, and new investigational therapies are exploring gene editing and protein restoration. Additionally, cardiomyopathy, a major complication, requires regular monitoring and management. Conclusion: Duchenne muscular dystrophy remains a challenging condition with significant impact on patients and their families. Early diagnosis and intervention are essential for improving outcomes, while ongoing research offers hope for more effective therapies. Effective management includes a multidisciplinary approach focusing on pharmacological, physical, and cardiac care.

Early Biomarkers for Detecting Subclinical Exposure to Fumonisin B1, Deoxynivalenol, and Zearalenone in Broiler Chickens.

Identifying biomarkers of mycotoxin effects in chickens will provide an opportunity for early intervention to reduce the impact of mycotoxicosis. This study aimed to identify whether serum enzyme concentrations, gut integrity, and liver miRNAs can be potential biomarkers for fumonisin B1 (FB1), deoxynivalenol (DON), and zearalenone (ZEA) toxicity in broiler birds as early as 14 days after exposure. A total of 720 male broiler chicks were distributed to six treatment groups: T1: control group (basal diet), T2 (2 FB1 + 2.5 DON + 0.9 ZEA), T3 (5 FB1 + 0.4 DON + 0.1 ZEA), T4 (9 FB1 + 3.5 DON + 0.7 ZEA), T5 (17 FB1 + 1.0 DON + 0.2 ZEA), and T6 (21 FB1 + 3.0 DON + 1.0 ZEA), all in mg/kg diet. On d14, there were no significant differences in the body weight gain (BWG) of mycotoxin treatment groups when compared to the control (p > 0.05), whereas on d21, T6 birds showed significantly reduced BWG compared to the control (p < 0.05). On d14, birds in T6 showed significant upregulation of liver miRNAs, gga-let-7a-5p (14.17-fold), gga-miR-9-5p (7.05-fold), gga-miR-217-5p (16.87-fold), gga-miR-133a-3p (7.41-fold), and gga-miR-215-5p (6.93-fold) (p < 0.05) and elevated serum fluorescein isothiocyanate-dextran (FITC-d) concentrations, aspartate aminotransferase (AST), and creatine kinase (CK) levels compared to the control (p < 0.05). On d21, T2 to T6 birds exhibited reduced serum phosphorus, glucose, and potassium, while total protein, FITC-d, AST, and CK levels increased compared to control (p < 0.05). These findings suggest that serum FITC-d, AST, CK, and liver miRNAs could serve as biomarkers for detecting mycotoxin exposure in broiler chickens.

The limited clinical utility of a routine creatine kinase (CK) on admission to a psychiatric inpatient unit

BackgroundCreatine kinase (CK) is an intracellular enzyme expressed most commonly in tissues such as skeletal muscle. CK can be used as an investigation to support the diagnosis of conditions such as neuroleptic malignant syndrome (NMS), a rare idiosyncratic drug reaction – classically to antipsychotic medications – which can be fatal. Routine screening of CK in psychiatric inpatients is a known practice, but its value is uncertain. We aimed to ascertain whether such screening resulted in new diagnoses of NMS or other conditions, and changes in clinical management.MethodsUsing an electronic case register, we conducted a descriptive retrospective cohort study, identifying all psychiatric inpatient admissions in a South London mental health trust over a four-year period where a CK test was conducted within 48 h of admission. We extracted the demographic and clinical characteristics (e.g., diagnosis) of those who met inclusion criteria. Free-text review was performed on all those with a CK potentially suggestive of NMS (CK ≥ 4x upper limit of normal reference range (ULN)) to determine the impact of this abnormal result on subsequent management and diagnosis (including NMS if identified).ResultsOf 14,236 inpatient episodes in the specified window, 2358 (16.6%) had a CK test within 48 h of admission. This was ≥ 4x ULN in 327 (13.8%) cases (free-text successfully reviewed in 318). There were no cases of NMS identified. An abnormal CK result led to a new alternative diagnosis, such as dehydration or catatonia, in only 14 patients (4.4% raised CK sample, 0.6% total CK sample). Impact on subsequent management appeared limited, with the most common adjustment being an increase in frequency of physical observations in 47 instances (14.8%).ConclusionsThe clinical utility of untargeted screening using a serum CK for psychiatric inpatients appears limited, with poor specificity in detection of NMS and a minimal impact on subsequent clinical management.