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Biomolecules Jun 2024De-differentiation and subsequent increased proliferation and inflammation of vascular smooth muscle cells (VSMCs) is one of the mechanisms of atherogenesis. Maintaining...
De-differentiation and subsequent increased proliferation and inflammation of vascular smooth muscle cells (VSMCs) is one of the mechanisms of atherogenesis. Maintaining VSMCs in a contractile differentiated state is therefore a promising therapeutic strategy for atherosclerosis. We have reported the 18-base myogenetic oligodeoxynucleotide, iSN04, which serves as an anti-nucleolin aptamer and promotes skeletal and myocardial differentiation. The present study investigated the effect of iSN04 on VSMCs because nucleolin has been reported to contribute to VSMC de-differentiation under pathophysiological conditions. Nucleolin is localized in the nucleoplasm and nucleoli of both rat and human VSMCs. iSN04 without a carrier was spontaneously incorporated into VSMCs, indicating that iSN04 would serve as an anti-nucleolin aptamer. iSN04 treatment decreased the ratio of 5-ethynyl-2'-deoxyuridine (EdU)-positive proliferating VSMCs and increased the expression of α-smooth muscle actin, a contractile marker of VSMCs. iSN04 also suppressed angiogenesis of mouse aortic rings ex vivo, which is a model of pathological angiogenesis involved in plaque formation, growth, and rupture. These results demonstrate that antagonizing nucleolin with iSN04 preserves VSMC differentiation, providing a nucleic acid drug candidate for the treatment of vascular disease.
Topics: Nucleolin; Animals; RNA-Binding Proteins; Muscle, Smooth, Vascular; Aptamers, Nucleotide; Cell Proliferation; Phosphoproteins; Cell Differentiation; Humans; Rats; Myocytes, Smooth Muscle; Mice; Cells, Cultured; Oligodeoxyribonucleotides; Male; Rats, Sprague-Dawley; Mice, Inbred C57BL
PubMed: 38927112
DOI: 10.3390/biom14060709 -
Biomolecules Jun 2024Abdominal aortic aneurysm (AAA) is a progressive dilatation of the aorta that can lead to aortic rupture. The pathophysiology of the disease is not well characterized... (Review)
Review
Abdominal aortic aneurysm (AAA) is a progressive dilatation of the aorta that can lead to aortic rupture. The pathophysiology of the disease is not well characterized but is known to be caused by the general breakdown of the extracellular matrix within the aortic wall. In this comprehensive literature review, all current research on proteins that have been investigated for their potential prognostic capabilities in patients with AAA was included. A total of 45 proteins were found to be potential prognostic biomarkers for AAA, predicting incidence of AAA, AAA rupture, AAA growth, endoleak, and post-surgical mortality. The 45 proteins fell into the following seven general categories based on their primary function: (1) cardiovascular health, (2) hemostasis, (3) transport proteins, (4) inflammation and immunity, (5) kidney function, (6) cellular structure, (7) and hormones and growth factors. This is the most up-to-date literature review on current prognostic markers for AAA and their functions. This review outlines the wide pathophysiological processes that are implicated in AAA disease progression.
Topics: Aortic Aneurysm, Abdominal; Humans; Biomarkers; Prognosis
PubMed: 38927064
DOI: 10.3390/biom14060661 -
Journal of Cardiothoracic Surgery Jun 2024Following an acute myocardial infarction (AMI), surgery for left ventricular free wall rupture (LVFWR) and ventricular septal rupture (VSR) has a high in-hospital...
BACKGROUND
Following an acute myocardial infarction (AMI), surgery for left ventricular free wall rupture (LVFWR) and ventricular septal rupture (VSR) has a high in-hospital mortality rate, which has not improved significantly over time. Unloading the LV is critical to preventing excessive stress on the repair site and avoiding problems such as bleeding, leaks, patch dehiscence, and recurrence of LVFWR and VSR because the tissue is so fragile. We present two cases of patients who used Impella 5.5 for LV unloading following emergency surgery for AMI mechanical complications.
CASE PRESENTATION
A 76-year-old male STEMI patient underwent fibrinolysis of the distal right coronary artery. Three days later, he passed out and went into shock. Echocardiography revealed a cardiac tamponade. We found an oozing-type LVFWR on the posterolateral wall and treated it with a non-suture technique using TachoSil. Before the patient was taken off CPB, Impella 5.5 was inserted into the LV via a 10 mm synthetic graft connected to the right axillary artery. We kept the flow rate above 4.0 to 4.5 L/min until POD 3 to reduce LV wall tension while minimizing pulsatility. On POD 6, we weaned the patient from Impella 5.5. A postoperative cardiac CT scan showed no contrast leakage from the LV. However, a cerebral hemorrhage on POD 4 during heparin administration complicated his hospitalization. Case 2: A diagnosis of cardiogenic shock caused by STEMI occurred in an 84-year-old male patient, who underwent PCI of the LAD with IABP support. Three days after PCI, echocardiography revealed VSR, and the patient underwent emergency VSR repair with two separate patches and BioGlue applied to the suture line between them. Before weaning from CPB, we implanted Impella 5.5 in the LV and added venoarterial extracorporeal membrane oxygenation (VA-ECMO) support for right heart failure. The postoperative echocardiography revealed no residual shunt.
CONCLUSIONS
Patients undergoing emergency surgery for mechanical complications of AMI may find Impella 5.5 to be an effective tool for LV unloading. The use of VA-ECMO in conjunction with Impella may be an effective strategy for managing VSR associated with concurrent right-sided heart failure.
Topics: Humans; Male; Aged; Heart-Assist Devices; Myocardial Infarction; Heart Ventricles; Heart Rupture, Post-Infarction; Ventricular Septal Rupture; Echocardiography; Postoperative Complications
PubMed: 38926884
DOI: 10.1186/s13019-024-02879-5 -
Scientific Reports Jun 2024During metastatic dissemination, circulating tumour cells (CTCs) enter capillary beds, where they experience mechanical constriction forces. The transient and persistent...
During metastatic dissemination, circulating tumour cells (CTCs) enter capillary beds, where they experience mechanical constriction forces. The transient and persistent effects of these forces on CTCs behaviour remain poorly understood. Here, we developed a high-throughput microfluidic platform mimicking human capillaries to investigate the impact of mechanical constriction forces on malignant and normal breast cell lines. We observed that capillary constrictions induced nuclear envelope rupture in both cancer and normal cells, leading to transient changes in nuclear and cytoplasmic area. Constriction forces transiently activated cGAS/STING and pathways involved in inflammation (NF-κB, STAT and IRF3), especially in the non-malignant cell line. Furthermore, the non-malignant cell line experienced transcriptional changes, particularly downregulation of epithelial markers, while the metastatic cell lines showed minimal alterations. These findings suggest that mechanical constriction forces within capillaries may promote differential effects in malignant and normal cell lines.
Topics: Humans; Breast Neoplasms; Female; Neoplastic Cells, Circulating; Cell Line, Tumor; Capillaries; Cell Nucleus; Neoplasm Metastasis; Nuclear Envelope
PubMed: 38926422
DOI: 10.1038/s41598-024-64733-x -
International Journal of Surgery Case... Jun 2024Isolated tibiotalar dislocation is an extremely rare injury. They are most often caused by high-energy trauma.
INTRODUCTION
Isolated tibiotalar dislocation is an extremely rare injury. They are most often caused by high-energy trauma.
CASE PRESENTATION
The authors report the case of an acute pure posteromedial tibiotalar joint dislocation in a 45-year-old patient, which occurred as a result of a road traffic accident. The reduction was performed as an emergency procedure under general anesthesia, followed by a 6-week cast immobilization. Twenty months after the injury, at the last follow-up, a very good functional result was observed, with a stable and painless ankle and satisfactory mobility.
DISCUSSION
A pure dislocation of the tibiotalar joint without an associated fracture is a rare injury. The posterior type is the most common dislocation. Treatments include close reduction, short leg cast immobilization, and open dislocation. However, certain factors can lead to unfavorable outcomes, such as delayed therapy, damage to the inferior tibiotalar ligaments, anterior tibial artery rupture, and soft tissue damage.
CONCLUSION
It is rare for a tibiotalar joint dislocations to occur as an isolated injury. The necessity of immediate orthopedic intervention in the management of this lesion is demonstrated by our observation.
PubMed: 38924923
DOI: 10.1016/j.ijscr.2024.109933 -
Veterinary Sciences Jun 2024A one-year-old female miniature goat was presented to an emergency service after calving a dead goatling. Physical and ultrasonographic examination revealed the presence...
A one-year-old female miniature goat was presented to an emergency service after calving a dead goatling. Physical and ultrasonographic examination revealed the presence of a viable fetus; therefore, the goat was submitted to an emergency cesarean section. In the postoperative period, the animal had septic peritonitis caused by and . Both bacterial strains showed contrasting antimicrobial resistance profiles. Laparohysterectomy and abdominal cavity lavage were performed, but, once the animal had adhesions and necrotic lesions in abdominal organs, euthanasia was executed. A post-mortem examination revealed fibrino-necrotic septic peritonitis secondary to uterine rupture. To the authors' knowledge, this is the first detailed report of polymicrobial septic peritonitis in a miniature goat and the first report of septic peritonitis caused by and .
PubMed: 38922015
DOI: 10.3390/vetsci11060268 -
Tomography (Ann Arbor, Mich.) Jun 2024Cystic echinococcosis is a zoonotic parasitic disease that affects the liver in more than 70% of cases, and there is still an underestimated incidence in endemic areas.... (Review)
Review
Cystic echinococcosis is a zoonotic parasitic disease that affects the liver in more than 70% of cases, and there is still an underestimated incidence in endemic areas. With a peculiar clinical presentation that ranges from paucisymptomatic illness to severe and possibly fatal complications, quality imaging and serological studies are required for diagnosis. The mainstay of treatment to date is surgery combined with antiparasitic agents. The surgical armamentarium consists of open and laparoscopic procedures for selected cases with growing confidence in parenchyma-sparing interventions. Endoscopic retrograde cholangiopancreatography (ERCP) is extremely useful for the diagnosis and treatment of biliary fistulas. Recent relevant studies in the literature are reviewed, and two complex cases are presented. The first patient underwent open surgery to treat 11 liver cysts, and during the follow-up, a right pulmonary cyst was diagnosed that was treated by minimally invasive surgery. The second case is represented by the peritoneal rupture of a giant liver cyst in a young woman who underwent laparoscopic surgery. Both patients developed biliary fistulas that were managed by ERCP. Both patients exhibited a non-specific clinical presentation and underwent several surgical procedures combined with antiparasitic agents, highlighting the necessity of customized treatment in order to decrease complications and successfully cure the disease.
Topics: Female; Humans; Biliary Fistula; Cholangiopancreatography, Endoscopic Retrograde; Echinococcosis, Hepatic; Laparoscopy; Liver; Tomography, X-Ray Computed
PubMed: 38921947
DOI: 10.3390/tomography10060070 -
Biomimetics (Basel, Switzerland) Jun 2024Acute cardiovascular events result from clots caused by the rupture and erosion of atherosclerotic plaques. This paper aimed to produce a functional biomimetic hydrogel...
Acute cardiovascular events result from clots caused by the rupture and erosion of atherosclerotic plaques. This paper aimed to produce a functional biomimetic hydrogel of the neointimal layer of the atherosclerotic plaque that can support thrombogenesis upon exposure to human blood. A biomimetic hydrogel of the neointima was produced by culturing THP-1-derived foam cells within 3D collagen hydrogels in the presence or absence of atorvastatin. Prothrombin time and platelet aggregation onset were measured after exposure of the neointimal models to platelet-poor plasma and washed platelet suspensions prepared from blood of healthy, medication-free volunteers. Activity of the extrinsic coagulation pathway was measured using the fluorogenic substrate SN-17. Foam cell formation was observed following preincubation of the neointimal biomimetic hydrogels with oxidized LDL, and this was inhibited by pretreatment with atorvastatin. The neointimal biomimetic hydrogel was able to trigger platelet aggregation and blood coagulation upon exposure to human blood products. Atorvastatin pretreatment of the neointimal biomimetic layer significantly reduced its pro-aggregatory and pro-coagulant properties. In the future, this 3D neointimal biomimetic hydrogel can be incorporated as an additional layer within our current thrombus-on-a-chip model to permit the study of atherosclerosis development and the screening of anti-thrombotic drugs as an alternative to current animal models.
PubMed: 38921252
DOI: 10.3390/biomimetics9060372 -
Cureus Jun 2024A femoral hernia containing the appendix within the sac is known as De Garengeot hernia. This condition is relatively rare but is important to recognize because it...
A femoral hernia containing the appendix within the sac is known as De Garengeot hernia. This condition is relatively rare but is important to recognize because it combines the complications of both femoral hernia and acute appendicitis, which are two distinct surgical emergencies. Clinical findings of a strangulated or incarcerated hernia may obscure signs of acute appendicitis. The presence of the inflamed appendix within the femoral hernia sac complicates the management of both conditions and requires careful surgical planning. We report a case of an 87-year-old female with De Garengeot hernia, complicated by perforated appendicitis and strangulated small bowel with perforation.
PubMed: 38919861
DOI: 10.7759/cureus.62994 -
AJOG Global Reports May 2024In vitro fertilization is the most used assisted reproductive technology in the United States that is increasing in efficiency and in demand. Certain states have...
BACKGROUND
In vitro fertilization is the most used assisted reproductive technology in the United States that is increasing in efficiency and in demand. Certain states have mandated coverage that enable individuals with low income to undergo in vitro fertilization treatment.
OBJECTIVE
This study aimed to evaluate if socioeconomic status has an impact on the perinatal outcomes in in vitro fertilization pregnancies. We hypothesized that with greater coverage there may be an alleviation of the financial burden of in vitro fertilization that can facilitate the application of evidence-based practices.
STUDY DESIGN
This was a retrospective, population-based, observational study that was conducted in accordance with the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database over the 6-year period from 2008 to 2014 during which period 10,000 in vitro fertilization deliveries were examined. Maternal outcomes of interest included preterm prelabor rupture of membranes, preterm birth (ie, before 37 weeks of gestation), placental abruption, cesarean delivery, operative vaginal delivery, spontaneous vaginal delivery, maternal infection, chorioamnionitis, hysterectomy, and postpartum hemorrhage. Neonatal outcomes included small for gestational age neonates, defined as birthweight <10th percentile, intrauterine fetal death, and congenital anomalies.
RESULTS
Our study found that the socioeconomic status did not have a statistically relevant effect on the perinatal outcomes among women who underwent in vitro fertilization to conceive after adjusting for the potential confounding effects of maternal demographic, preexisting clinical characteristics, and comorbidities.
CONCLUSION
The literature suggests that in states with mandated in vitro fertilization coverage, there are better perinatal outcomes because, in part, of the increased use of best in vitro fertilization practices, such as single-embryo transfers. Moreover, the quality of medical care in states with coverage is in the highest quartile in the country. Therefore, our findings of equivalent perinatal outcomes in in vitro fertilization care irrespective of socioeconomic status possibly suggests that a lack of access to quality medical care may be a factor in the health disparities usually seen among individuals with lower socioeconomic status.
PubMed: 38919707
DOI: 10.1016/j.xagr.2024.100329