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This meta-analysis was conducted to summarize the effects of n-3 polyunsaturated fatty acid (n-3 PUFA) on metabolic status including insulin metabolism and lipid metabolism in women with polycystic ovary syndrome (PCOS) by randomized controlled trials (RCTs). Four mainstream databases including PubMed, Cochrane Library, Embase and Web of Science were searched from their inception to October 2021. The registration number of this study was CRD42021285233. The quality assessment was performed referring the Cochrane Risk of Bias Tool. Mean differences (MD) and 95% confidence intervals (CIs) were generated for continuous variables by meta-analysis. Subgroup analyses were performed based on study duration (≤ 8 weeks or > 8 weeks), the source of n-3 PUFA (marine derived or plant origins) and dosage of n-3 PUFA (≤ 1000 mg/d or > 1000 mg/d). Eventually, 11 RCTs reporting 816 patients were enrolled. Compared with control group, n-3 PUFA treatment decreased waist circumference (MD = -2.76, 95% CI: -3.82 to -1.69; p < 0.00001), fasting plasma glucose (MD = -3.91, 95% CI: -5.69 to -2.13; p < 0.0001), fasting insulin (MD = -2.45, 95% CI: -3.19 to -1.71; p < 0.00001), homeostatic model assessment of insulin resistance (MD = -0.45, 95% CI: -0.80 to -0.11; p = 0.01), triglyceride (MD = -9.33, 95% CI: -10.56 to -8.10; p < 0.00001), total cholesterol (MD = -12.32, 95% CI: -19.15 to -5.50; p = 0.0004), low-density lipoprotein cholesterol (MD = -10.53, 95% CI: -19.31 to -1.75; p = 0.02), and increase quantitative insulin sensitivity check index (MD = 0.01, 95% CI: 0.01 to 0.02; p < 0.00001), Adiponectin (MD = 1.46, 95% CI: 1.12 to 1.80; p < 0.00001) in PCOS patients. However, n-3 PUFA failed to change body weight, body mass index, high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and hs-CRP in the overall analysis. Further subgroup analyses showed that supplements of n-3 PUFA for more than 8 weeks is more conducive to improve the metabolic status in insulin resistance and lipid profiles. The meta-analysis demonstrates that n-3 PUFA may be an effective intervention for alleviating metabolic status in PCOS. Hence, we recommend PCOS patients replenish n-3 PUFA with duration > 8 weeks regardless of the source and the dosage to retard the pathogenesis of PCOS related metabolic diseases. [ABSTRACT FROM AUTHOR]

Background: Dystrophinopathy, a common neuromuscular disorder, includes Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Many researches are currently ongoing to develop curative approaches, which results in an urgent need for biomarkers of disease progression and treatment response. This study investigated whether the serum creatinine (SCRN) level can be used as a biomarker of disease progression in dystrophinopathy.Methods: We enrolled 377 male patients with dystrophinopathy and 520 male non-dystrophinopathy controls in a cross-sectional study. From this cohort, 113 follow-up patients were enrolled in a longitudinal study. Patients' demographic information, motor function, muscle fatty infiltration, and muscle dystrophin levels were evaluated. We investigated correlations between these parameters and SCRN levels, and determined changes in SCRN levels with maturation and with motor function changes.Results: Our results showed SCRN levels correlated with motor function (FDR < 0.001) and timed test results (FDR between < 0.001-0.012), as well as with muscle fatty infiltration (FDR < 0.001) and dystrophin levels (FDR = 0.015 and 0.001). SCRN levels increased with maturation in control individuals; it slowly increased with maturation in patients with BMD but decreased generally with maturation in patients with DMD. The longitudinal study further demonstrated that SCRN levels were associated with motor function.Conclusions: These findings indicated that the SCRN level is a promising biomarker for assessing disease progression in dystrophinopathy and could be used as a potential outcome measure in clinical trials. [ABSTRACT FROM AUTHOR]

Background: Mutations in the DMD gene encoding dystrophin—a critical structural element in muscle cells—cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD. Methods: In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46–54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors. Results: Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member β-dystroglycan. Conclusions: We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases. [ABSTRACT FROM AUTHOR]

Background: Mutations in the DMD gene encoding dystrophin—a critical structural element in muscle cells—cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD. Methods: In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46–54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors. Results: Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member β-dystroglycan. Conclusions: We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases. [ABSTRACT FROM AUTHOR]