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Ehlers-Danlos syndrome (EDS) is a rare and diverse group of heritable connective tissue disorders. Gastrointestinal manifestations and abdominal pain are frequent in most subtypes of EDS. Conservative treatment is the standard of care.
A 43-year-old female patient with genetically confirmed EDS classic subtype presented with diffuse gastrointestinal symptoms (bloating, belching and pain) that were controlled by the patient through inclined posture and external abdominal compression. A standard abdominoplasty with rectus muscle plication and mesh implantation lead immediately to complete relief of symptoms, which allowed the patient to assume an upright posture and resume all daily activities again. After 7 years, the patient was again seen with severe, persistent abdominal pain and inclined posture related to right lumbar herniations, as confirmed by MRI. However, there was no recurrence of the previous abdominal midline weakness and related gastrointestinal symptoms. Following lumbar hernia repair and mesh implantation, the patient was free of abdominal pain and resumed an upright posture again.
Although conservative treatment of EDS is primarily recommended and most surgeons are reluctant to operate on these patients except in life threatening situations, we present the successful surgical relief of disabling abdominal symptoms.
Regarding the variability and complexity of symptoms in different subtypes of EDS, a personalized multimodal treatment including surgical approaches should be considered and achieved a significant and long-lasting improvement in quality of life in our patient.
Regarding the variability and complexity of symptoms in different subtypes of EDS, a personalized multimodal treatment including surgical approaches should be considered and achieved a significant and long-lasting improvement in quality of life in our patient.
Gastroesophageal (GE) junction injuries are rare in the pediatric population. A complete GE junction separation in a child secondary to trauma has not reported in the literature yet.
A 14-year-old boy presented with a complete GE junction avulsion after a near-drowning experience. He underwent immediate damage control surgery and delayed gastric pull-up esophageal reconstruction in 3-months. Navitoclax At the most recent clinic visit 5 months from the reconstruction, he can tolerate a regular diet without difficulty and is gaining weight and recovering well.
Complete GE junction injuries and avulsions are rare with limited data to guide management. These injuries are associated with mortality rates from 25% to 33%, therefore, high index of suspicion, prompt recognition and careful surgical planning is needed for favorable outcomes.
Complete GE junction injuries and avulsions are rare with limited data to guide management. These injuries are associated with mortality rates from 25% to 33%, therefore, high index of suspicion, prompt recognition and careful surgical planning is needed for favorable outcomes.
Inhibiting apoptosis of trophoblasts in women with gestational diabetes mellitus (GDM) is expected to guarantee adequate nutrition for the fetus and avoid abortion. MiR-193b is one of the most downregulated miRNAs in GDM patients. However, less is known about the role of miR-193b in autophagy and apoptosis in GDM patients.
We detected the expression of miR-193b in GDM patients. Then, we cultured human trophoblasts (HTR8 cells) with high glucose (HG) to simulate a diabetic environment in vitro, and further explored the effects of miR-193b on apoptosis and autophagy of HG-treated HTR8 cells.
The expression of miR-193b was significantly downregulated in the peripheral blood of GDM patients compared with healthy controls, and decreased miR-193b caused apparent autophagy and a substantially high apoptosis rate in HG-treated HTR8 cells. These effects were reversed by enhancing miR-193b expression or using the autophagy inhibitor 3-MA. Inhibiting miR-193b induced the pro-autophagic, cytostatic, and pro-apoptotic effects reduced by 3-MA in HTR8 cells upon HG treatment. Moreover, the expression of insulin-like growth factor-binding protein 5 (IGFBP5) was upregulated notably in the peripheral blood of GDM patients, and IGFBP5 appears to represent a direct miR-193b target. Note that silencing IGFBP5 blocked autophagy and apoptosis in HG-treated HTR8 cells, an effect that was diminished by inhibiting miR-193b.
Our data indicate that aberrantly low expression of miR-193b in HG-induced trophoblasts results in massive apoptosis events by upregulating IGFBP5-induced autophagy, which may trigger GDM. Therefore, miR-193b may became a potential target for GDM therapy.
Our data indicate that aberrantly low expression of miR-193b in HG-induced trophoblasts results in massive apoptosis events by upregulating IGFBP5-induced autophagy, which may trigger GDM. Therefore, miR-193b may became a potential target for GDM therapy.
MiR-124-3p is one of the aberrantly expressed miRNAs in the placentas of patients with preeclampsia (PE), a severe obstetric complication characterised by hypertension and proteinuria. This study aimed to investigate the role of miR-124-3p in the invasion, migration and death of trophoblast cells and explore the potential mechanisms.
MiR-124-3p expression in placental tissues was compared with that in normal placenta. HTR8/SVneo cells were then transfected with miR-124-3p mimics to examine cellular apoptosis, migration and invasion. Furthermore, the expression of pyroptosis-related molecular NLRP3, Pro-caspase1, caspase1, IL-1β and GSDMD was examined with Western blot. Dual luciferase reporter assay was performed to confirm that placental growth factor (PLGF) is a direct target of miR-124-3p, and HTR-8/SVneo cells were transfected with small interfering RNA PLGF (siPLGF) to determine whether PLGF knockdown promotes HTR-8/SVneo pyroptosis. Finally, intracellular ROS was diminished with N-acetyl-l-cysteine (NAC) to observe whether the pro-pyroptosis effect of PLGF knockdown is alleviated.
Results in this study showed that miR-124-3p expression was remarkably increased in the placenta of patients with PE. Moreover, the transfection of miR-124-3p mimics in trophoblastic cells significantly decreased cell migration and invasion but increased cell apoptosis and the expression of NLRP3, pro-caspase1, caspase1, IL-1β and GSDMD. Therefore, PLGF was confirmed as a direct target of miR-124-3p. Finally, siPLGF transfection can mimic the effects of miR-124-3p, and NAC can inhibit this effect.
In summary, miR-124-3p is upregulated in PE, and in vitro functional analysis revealed that this mRNA inhibits trophoblast invasion and migration but promotes cell pyroptosis partly via the PLGF-ROS pathway.
In summary, miR-124-3p is upregulated in PE, and in vitro functional analysis revealed that this mRNA inhibits trophoblast invasion and migration but promotes cell pyroptosis partly via the PLGF-ROS pathway.
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