Baicalein alleviates palmitic acid-induced endothelial cell dysfunction via inhibiting endoplasmic reticulum stress.

OBJECTIVE: Endothelial cells play a critical role in maintaining vascular function and kinetic homeostasis, but excessive accumulation of palmitic acid (PA) may lead to endoplasmic reticulum stress and trigger endothelial cell dysfunction. Baicalin (BCL), a natural plant extract, has received widespread attention for its biological activities in anti-inflammation and anti-oxidative stress. However, the mechanism of BCL on PA-induced endothelial cell dysfunction is unclear. Therefore, the aim of this study was to investigate whether BCL could inhibit PA-induced endoplasmic reticulum stress and thus attenuate endothelial cell dysfunction. METHODS: Human umbilical vein endothelial cells (HUVECs) were divided into Control, PA, PA + BCL-10 µM, PA + BCL-20 µM, and PA + BCL-50 µM groups. The PA group was treated with PA (200 µM), while the PA + BCL groups were co-treated with different concentrations of BCL (10 µM, 20 µM, 50 µM) for 24 hours. Cell viability was detected by MTT. Cell migration ability was determined by Transwell assay, apoptosis level by flow cytometry, and tube formation ability by tube formation assay. Finally, the levels of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and angiogenesis-related proteins (VEGFA and FGF2) were detected by western blot, MMP-9, as well as the protein levels of endoplasmic reticulum stress biomarkers (GRP78, CHOP, PERK, and ATF4). RESULTS: The results at the cellular level showed that cell viability, migration ability and tube formation ability of PA-induced HUVECs were significantly reduced, while apoptosis level was significantly increased. However, administration of different concentrations of BCL significantly enhanced PA-induced cell viability, migration ability and tube formation ability of HUVECs while inhibiting apoptosis. The results of protein levels showed that the protein levels of Bax and cleaved caspase-3 were observably up-regulated in the cells of the PA group, while the protein level of Bcl-2 was significantly down-regulated; compared with the PA group, the protein levels of Bax and cleaved caspase-3 were much lower and the Bcl-2 protein level was much higher in the PA + BCL group. Additionally, the protein levels of VEGFA, FGF2 and MMP-9 were raised and those of GRP78, CHOP, PERK and ATF4 were lowered in the PA + BCL group of cells in a concentration-dependent manner. CONCLUSION: BCL significantly attenuates PA-induced endothelial cell dysfunction by inhibiting endoplasmic reticulum stress.

Therapeutic effectiveness of tuberculous aneurysm and risk factors for mortality: a systematic review.

OBJECTIVE: This study aimed to determine the therapeutic effectiveness of tuberculous aortic aneurysms (TBAAs) and the risk factors for mortality. METHODS: We reviewed all case reports of TBAAs treated with open surgery or endovascular aneurysm repair (EVAR) from online database in 1996-2021. Only thoracic and abdominal aortic aneurysms were included. RESULTS: Eighty cases of open surgery and 42 cases of EVAR were included. The 2-year mortality and perioperative mortality rates of open surgery were 11.3% and 10.0%, respectively. Emergent open surgery had a significantly higher mortality (25.0%) than non-emergent open surgery (6.7%). In the EVAR group, 2-year mortality, perioperative mortality, and TBAA-related mortality were 16.7%, 4.8%, and 10.0%, respectively. Patients with typical tuberculosis (TB) symptoms before EVAR had a significantly higher TBAA-related mortality (35.0%) than patients with no typical TB symptoms before EVAR (0%). In the open surgery group, the rate of TB recurrence (2.7% vs 2.4%) and aneurysm recurrence (8.1% vs 7.3%) were quite close between preoperative anti-TB-treated and postoperative anti-TB-treated cases. However, in the EVAR group, TB recurrence (8.7% vs 0%) and aneurysm recurrence (12.5% vs 6.25%) were more common in postoperative anti-TB-treated cases. CONCLUSION: Open surgery was accompanied by higher perioperative mortality, whereas EVAR was followed with higher TBAA-related mortality. Emergent surgical choices of open surgery may be associated with high perioperative mortality. Typical TB symptoms before EVAR are a significant risk factor for mortality after EVAR. Early anti-TB treatment should be administered if EVAR is the surgical option.

Clinical features of tuberculous pseudoaneurysm and risk factors for mortality.

OBJECTIVES: The objective of this study was to determine the clinical features of tuberculous aneurysms and risk factors for mortality. METHODS: We reviewed all case reports of tuberculous aneurysms in the English literature from January 2000 to December 2020. The clinical features and possible risk factors for mortality were recorded and analyzed. RESULTS: In total, 174 cases of tuberculous aneurysms were identified. The morbidity of men was more than twice that of women. Male patients (51.47 ± 20.67 years) were older than female patients (39.52 ± 20.23 years; P < .05). The rupture rate in women (69.2%) was higher than that in men (48.8%). Tuberculosis (TB)-induced aneurysms often spontaneously ruptured 1.41 to 3.01 months after the onset of TB symptoms without any treatment, and Bacillus Calmette-Guerin (BCG)-induced aneurysms often spontaneously ruptured 10.51 to 26.49 months after BCG administration. The morbidity of large artery aneurysms was nearly twice that of middle artery aneurysms. However, middle artery aneurysms were more likely to rupture (75.4%) than large artery aneurysms (43.5%; P < .05). The rupture rate of BCG-induced aneurysms (37.0%) was lower than that of TB-induced aneurysms, regardless of whether there was a TB history (56.7%) or not (57.7%). Symptoms of TB occurred in 63.2% of patients, but only 8.6% of patients had both symptoms of TB and aneurysmal mass effects. Pain was the most common atypical clinical manifestation (50.0%). The Cox proportional hazards regression analysis and Kaplan-Meier estimator showed that rupture and no combined therapy were risk factors for mortality. CONCLUSIONS: Tuberculous aneurysms seemingly shared the same demographic characteristics as common aneurysms. The clinical features of TB-induced aneurysms were different from those of BCG-induced aneurysms in terms of the aneurysm location and rupture rate. Tuberculous aneurysms may occur at any site of the cardiovascular system with a preponderance for large arteries. The changeable clinical manifestations were important index for diagnosis, but focusing only on clinical manifestations may lead to a missed diagnosis. The combination of anti-TB medications and surgery before aneurysm rupture may provide the best prognosis.

Alpha-lactose reverses liver injury via blockade of Tim-3-mediated CD8 apoptosis in sepsis.

In sepsis, the liver plays a crucial role in regulating immune responses and is also a target organ for immune-related injury. Despite the critical function of CD8+ T cells against opportunistic viral infections, the CD8 immune response in the liver during sepsis remains elusive. Here we found that Tim-3 is highly up-regulated in liver CD8+ T cells in a mouse cecal ligation and puncture model and in peripheral blood CD8+ T cells of human patients with sepsis. The expression of Tim-3 in liver CD8+ T cells displayed a bi-phasic pattern and deletion of Tim-3 led to reduction of CD8+ T cell apoptosis. Administration of α-lactose, a molecule with a similar structure to galactin-9, reduced Tim-3 expression and liver injury in sepsis. Our results demonstrate that targeting Tim-3 to boost CD8+ T cell immune response may offer an improved outcome in patients with sepsis.