Int J Med Sci
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Background: Preimplantation genetic testing for monogenic disease (PGT-M) has become an effective method for providing couples with the opportunity of a pregnancy with a baby free of spinal muscular atrophy (SMA). Multiple displacement amplification (MDA) overcomes the innate dilemma of very limited genetic material available for PGT-M. Objective: To evaluate the use of MDA, combined with haplotype analysis and mutation amplification, in PGT-M for families with SMA. ⋯ Among them, 5 SMA carriers were singleton live births and 3 SMA carriers had twin births. Conclusion: Careful handling during the MDA procedure can improve subsequent PCR efficiency and reduce the ADO rate. We suggest that this protocol is reliable for increasing the accuracy of the PGT-M for SMA.
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The aim of this study was to elucidate the role of fibroblasts in bisphosphonate-related osteonecrosis of the jaw (BRONJ), evaluating the effect of zoledronate, alendronate, and ibandronate on the proliferation of fibroblasts and on their expression of genes essential for fibroblast physiology. Human CCD-1064Sk epithelial fibroblast cells were incubated in culture medium with 10-5, 10-7, or 10-9 M zoledronate, alendronate, or ibandronate. The proliferative capacity of fibroblasts was determined by spectrophotometry (MTT) at 24 of culture. ⋯ The proliferation increase may be related to the rise in TGF-β1 and TGFβR1 expression detected after the treatment of cells with 10-9M of zoledronate, alendronate, or ibandronate. However, the expression of CTGF, DDR2, α-actin, fibronectin, and decorin decreased versus controls. The results of this in vitro study indicate that a very low BP dose (10-9 M) can significantly affect the physiology of fibroblasts, increasing their proliferative capacity and modulating the expression of multiple genes involved in their growth and differentiation.
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This study has two novel findings: it is not only the first to deduct potential genes involved in scleral growth repression upon atropine instillation from a prevention point of view, but also the first to demonstrate that only slight changes in scleral gene expression were found after atropine treatment as side effects and safety reasons of the eye drops are of concern. The sclera determines the final ocular shape and size, constituting of scleral fibroblasts as the principal cell type and the major regulator of extracellular matrix. The aim of our study was to identify differentially expressed genes and microRNA regulations in atropine-treated scleral fibroblasts that are potentially involved in preventing the onset of excessive ocular growth using next-generation sequencing and bioinformatics approaches. ⋯ Significant canonical pathways were correlated to inhibition of melatonin degradation, which was compatible with our clinical practice as atropine eye drops are instilled at night. Validation of the dysregulated genes with previous eye growth-related arrays and through microRNA-mRNA interaction predictions revealed the association of hsa-miR-2682-5p-KCNJ5 and hsa-miR-2682-5p-PRLR with scleral anti-remodeling and circadian rhythmicity. Our findings present new insights into understanding the anti-myopic effects of atropine, which may assist in prevention of myopia development.
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Objective: Currently, sorafenib is the main systemic chemotherapy drug for advanced stage of hepatocellular carcinoma (HCC). However, emerging data from some clinical HCC patients indicates that sorafenib alone has only moderate antitumor efficacy, and could not inhibit metastasis and progression of disease. MiR-221 plays a role in promoting tumorigenesis in HCC by inhibiting the expression of p27. ⋯ Results: AuNPs-anti-miR221 can enhance the effect of sorafenib in inhibiting cell proliferation via inactivating miR-221/p27/DNMT1 signaling pathway. Conclusions: Our results demonstrate that sorafenib combined with AuNPs-anti-miR221 treatment does effectively inhibit proliferation of HCC cell lines synergistically. These data suggest the AuNPs-anti-miR221 may be a promising chemosensitizer to sorafenib in the treatment of HCC.
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Introduction: Antibiotic use is an important risk factor for Clostridium difficile infection (CDI). Prior meta-analyses have identified antibiotics and antibiotic classes that pose the greatest risk for CDI; however, CDI epidemiology is constantly changing and contemporary analyses are needed. Objectives: The objective of this study was to evaluate the association between CDI and important antibiotic classes in recent years using the FDA Adverse Event Report System (FAERS). ⋯ CDI RORs (95%CI) for the antibiotic classes were (in descending order): lincosamides 46.95 (39.49-55.82), monobactams 29.97 (14.60-61.54), penicillin combinations 20.05 (17.39-23.12), carbapenems 19.16 (15.52-23.67), cephalosporins/ monobactams/carbapenems 17.28 (14.95-19.97), cephalosporins 15.33 (12.60-18.65), tetracyclines 7.54 (5.42-10.50), macrolides 5.80 (4.48-7.51), fluoroquinolones 4.94 (4.20-5.81), and trimethoprim-sulfonamides 3.32 (2.03-5.43). Conclusion: All antibiotic classes included in the study were significantly associated with CDI. Lincosamides (e.g., clindamycin) had the highest CDI ROR among the antibiotics evaluated in this study.