Label-free high frame rate imaging of circulating blood clots using a dual modal ultrasound and photoacoustic system

Deep vein thrombosis (DVT) is a disorder when a blood clot (thrombus) is formed in one of the deep veins. These clots detach from the original sites and circulate in the blood stream at high velocities. Diagnosing these blood clots at an early stage is necessary to decide the treatment strategy. For label-free, in vivo, and real-time detection, high framerate photoacoustic imaging can be used. In this work, a dual modal clinical ultrasound and photoacoustic (PA) system is used for the high framerate PA imaging of circulating blood clots in blood at linear velocities up to 107 cm/sec. Blood clot had 1.4 times higher signal-to-noise ratio (SNR) in the static mode and 1.3 times higher SNR compared to blood PA signal in the flow experiments. This work demonstrates that fast-moving circulating blood clots are easy to recognize against the background PA signal and may aid in early diagnosis.     

Features and incidence of thromboembolic disease: A comparative study between high and low altitude dwellers in Saudi Arabia

To estimate and compare the incidence of thromboembolic disease among patients who are clinically suspected for VTE among high and low altitude dwellers in Saudi Arabia. A prospective study conducted over two years (2011–2013) conducted in two different geographical areas in Saudi Arabia; Abha City and Riyadh City. Patients clinically suspected with deep vein thrombosis and pulmonary embolism was recruited to the study. A detailed social, medical and laboratory investigations were taken from all patients including lifestyle, occupation and smoking. A total of 234 patients participated in the study. There were 146 (62.4%) females and 88 (37.6%) males. Mean age was 51.7 years. A 56.8% incidence of DVT was seen among high altitude dwellers compared to 13.0% among low altitude dwellers. Also, a 12.6% incidence of PE was documented among high altitude dwellers, compared to 4.1% of the low altitude dwellers. VTE was significantly more among high altitude dwellers (81.9%) compared to low altitude dwellers (21.9%). Mean WBC count was significantly higher among the high altitude dwellers (10.8 ± 9.7 vs. 8.2 ± 3.4, p = 0.043). Mean platelet count was significantly higher among the high altitude dwellers compared to the low altitude dwellers (327.4 ± 162.4 vs. 212.0 ± 158.9, p = 0.005). The likelihood of developing VTE is greater among people who resided at moderate to high altitude for prolonged periods of time. The changes in the factors for coagulation including platelet counts may not reflect the true status of hypercoagulability especially if patients have stayed longer in high altitudes because of physiological adaptation to the environment.     

14‐3‐3ζ binds to and stabilizes phospho‐beclin 1S295 and induces autophagy in hepatocellular carcinoma cells

Data from The Cancer Genome Atlas (TCGA) indicate that the expression levels of 14‐3‐3ζ and beclin 1 (a key molecule involved in cellular autophagy) are up‐regulated and positively correlated with each other (R = .5, P < .05) in HCC tissues. Chemoresistance developed in hepatoma cancer cells is associated with autophagy initiation. This study aimed to explore 14‐3‐3ζ’s role in regulating autophagy in HCC cells, with a focus on beclin 1. The co‐localization of 14‐3‐3ζ and beclin 1 was detectable in primary HCC tissues. To simulate in vivo tumour microenvironment (hypoxia), CSQT‐2 and HCC‐LM3 cells were exposed to 2% oxygen for 24 hours. The protein levels of 14‐3‐3ζ and phospho‐beclin 1^S295 peaked at 12 hours following hypoxia. Meanwhile, the strongest autophagy flux occurred: LC3II was increased, and p62 was decreased significantly. By sequencing the coding area of BECN 1 gene of CSQT‐2 and HCC‐LM3 cells, we found that the predicted translational products of BECN 1 gene contained RLPS²⁹⁵VP (R, arginine; L, leucine; P, proline; S, serine; V, valine), a classic 14‐3‐3ζ binding motif. CO‐IP results confirmed that 14‐3‐3ζ bound to beclin 1, and this connection was markedly weakened when S²⁹⁵ was mutated into A²⁹⁵ (alanine). Further, 14‐3‐3ζ overexpression prevented phospho‐beclin 1^S295 from degradation and enhanced its binding to VPS34, whilst its knockdown accelerated the degradation. Additionally, 14‐3‐3ζ enhanced the chemoresistance of HCC cells to cis‐diammined dichloridoplatium by activating autophagy. Our work reveals that 14‐3‐3ζ binds to and stabilizes phospho‐beclin 1^S295 and induces autophagy in HCC cells to resist chemotherapy.