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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 -
Journal of Biomechanics Jun 2024Lumbrical muscles originate on the flexor digitorum profundus (FDP) tendons and, during fist making, they move in the same direction when FDP muscle produces maximal...
Lumbrical muscles originate on the flexor digitorum profundus (FDP) tendons and, during fist making, they move in the same direction when FDP muscle produces maximal proximal tendon gliding. Injuries of the bipennate lumbricals have been described when a shear force acts between the origins on adjacent tendons of the FDP, as they glide in opposite directions in asymmetric hand postures. Other structures of the deep flexors complex can be affected during this injury mechanism, due to the so-called quadriga effect, which can commonly occur during sport climbing practise. Biomechanical studies are needed to better understand the pathomechanism. A cadaveric study was designed to analyse the effects of load during the fourth lumbrical muscle injury mechanism. The amount of FDP tendon gliding and metacarpophalangeal (MCP) joint flexion of the 5th finger were calculated. Ten fresh-frozen cadaveric specimens (ten non-paired forearms and hands) were used. The specimens were placed on a custom-made loading apparatus. The FDP of the 5th finger was loaded, inducing isolated flexion of the 5th finger, until rupture. The rupture occurred in all specimens, under a load of 11 kg (SD 4.94), at 9.23 mm of proximal tendon gliding (SD 3.55) and at 21.4° (SD 28.91) of MCP joint flexion. Lumbrical muscle detachment from the 4th FDP was observed, from distal to proximal, and changes in FDP tendons at the distal forearm level too. The quadriga effect can lead to injury of the bipennate lumbrical muscles and the deep flexors complex in the hand and forearm.
PubMed: 38924964
DOI: 10.1016/j.jbiomech.2024.112196 -
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 -
Arteriosclerosis, Thrombosis, and... Jul 2024
Topics: Humans; Plaque, Atherosclerotic; Atherosclerosis; Rupture, Spontaneous; Disease Progression; Animals
PubMed: 38924440
DOI: 10.1161/ATVBAHA.124.319396 -
Arteriosclerosis, Thrombosis, and... Jul 2024Most abdominal aortic aneurysms (AAAs) are small with low rupture risk (<1%/y) when diagnosed but slowly expand to ≥55 mm and undergo surgical repair. Patients and... (Review)
Review
CLINICAL PROBLEM
Most abdominal aortic aneurysms (AAAs) are small with low rupture risk (<1%/y) when diagnosed but slowly expand to ≥55 mm and undergo surgical repair. Patients and clinicians require medications to limit AAA growth and rupture, but drugs effective in animal models have not translated to patients.
RECOMMENDATIONS FOR INCREASING TRANSLATION FROM MOUSE MODELS
Use models that simulate human AAA tissue pathology, growth patterns, and rupture; focus on the clinically relevant outcomes of growth and rupture; design studies with the rigor required of human clinical trials; monitor AAA growth using reproducible ultrasound; and perform studies in both males and females.
SUMMARY OF STRENGTHS AND WEAKNESSES OF MOUSE MODELS
The aortic adventitial elastase oral β-aminopropionitrile model has many strengths including simulating human AAA pathology and modeling prolonged aneurysm growth. The Ang II (angiotensin II) model performed less well as it better simulates acute aortic syndrome than AAA. The elastase plus TGFβ (transforming growth factor-β) blocking antibody model displays a high rupture rate, making prolonged monitoring of AAA growth not feasible. The elastase perfusion and calcium chloride models both display limited AAA growth.
Topics: Animals; Aortic Aneurysm, Abdominal; Disease Models, Animal; Humans; Aortic Rupture; Pancreatic Elastase; Mice; Aorta, Abdominal; Female; Disease Progression; Male
PubMed: 38924435
DOI: 10.1161/ATVBAHA.124.320823 -
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