Problems such as massive hemorrhage caused by uncontrolled drug dosage are the main significant obstacle in clinical thrombolytic therapy, which are prominently due to the lack of targeting and controlled...
Disability
and even death from acute thrombosis remain a grave
menace to public health. At present, the traditional drugs represented
by urokinase (UK) in clinical thrombolysis can cause side effects
of bleeding when the dosage is excess. Therefore, a more effective
and safer method of thrombolysis is urgently needed. In this paper,
a multifunctional dual-drug sequential release thrombolysis platform
(UK-UH@PDA@HMSNs) consisting of polydopamine (PDA)-modified hollow
mesoporous silicon (HMSNs) loading with UK and unfractionated heparin
(UH) was constructed with a double physical assistance (NIR-II and
bubbles). With the aid of near infrared-II (NIR-II, 1064 nm, 1.0 W
cm–2) laser, the photothermal effect of PDA could
be motivated to facilitate the UH release, thereby accelerating the
dissolution of thrombus. Afterward, the local hyperthermia effect
could expedite the phase transition of l-menthol in HMSNs
to generate bubbles to promote the release of UK, thereby realizing
the sequential release of two thrombolytic drugs. Importantly, this
method deftly conquered the inherent obstacle that UK and UH cannot
be combined directly. In vivo and in vitro experiments proved that the thrombolytic efficiency of UK-UH@PDA@HMSNs
stimulated by NIR-II was nearly 3 times than that of UK alone. Collectively,
the proposed dual physical assistance and sequential dual-drug delivery
system significantly improved the efficiency of thrombolysis under
the premise of limiting drug doses; the risk of death from intracranial
hemorrhage thus could be decreased radically.
Background
Previous studies have shown that Family with sequence similarity 134 member B (FAM134B) was involved in the occurrence and development of malignancy, however, the function and molecular mechanism of FAM134B in Hepatocellular Carcinoma (HCC) radiotherapy resistance remain unclear. Therefore, it may clinical effective to clarify the molecular mechanism and identify novel biomarker to overcome radiotherapy resistance in HCC.
Methods
The protein and mRNA expression of FAM134B were determined using Real-time PCR and Western blot, respectively. IHC assay was performed to investigate the association between FAM134B expression and the clinicopathological characteristics of 132 HCC patients. Functional assays, such as in situ model, colon formation, FACS, and Tunel assay were used to determine the oncogenic role of FAM134B in human HCC progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of FAM134B promotes radiation-sensitive in HCC cells.
Results
We noted that FAM134B was downregulated in HCC, which was correlated with the radiation resistance in patients with HCC. Overexpression of FAM134B contribute to radiation sensitive in HCC; however, inhibition of FAM134B confers HCC cell lines to radiation resistance both in vitro and in vivo. Moreover, we found that FAM134B interacts with FMS related receptor tyrosine kinase 3 (FLT3) and downregulation of FAM134B activated JAK/Stat3 signaling pathway. Importantly, pharmacological inhibition of JAK/Stat3 signaling pathway significantly counteracted downregulation of FAM134B-induced radiation resistance and enhanced radiation therapeutic efficacy in HCC.
Conclusions
Our findings suggest that FAM134B may be a potential therapeutic biomarker for the treatment of HCC patients with radiotherapy tolerance.
This research aimed to evaluate the therapeutic effect of edaravone on lower limb ischemia-reperfusion injury by MRI images of graph patch-based directional curvelet transform (GPBDCT), compression reconstruction algorithm. 200 patients with lower limb ischemia-reperfusion injury after replantation of severed limb were randomly divided into the observation group (edaravone treatment) and control group (Mailuoning injection treatment), with 100 cases in each group. MRI scanning and image processing using the GPBDCT algorithm were used to evaluate the therapeutic effect of the two groups of patients. The results showed that the signal noise ratio (SNR) (22.01), relative
l
2
norm error (RLNE) (0.0792), and matching degree
γ
(0.9997) of the compression and reconstruction algorithm based on GPBDCT were superior to those of the conventional compression and reconstruction algorithm (
P
<
0.05
). MRI examination showed that the decrease of bleeding signal after treatment in the observation group was superior to that in the control group. The levels of superoxide dismutase (SOD) (15 ± 2.02), malondialdehyde (MDA) (2.27 ± 1.02), B cell lymphoma-2 (Bcl-2) (8.5 ± 1.02), Bcl-2-associated X (Bax) (3.7 ± 0.42), and Caspase-3 protein (35.9 ± 5.42) in the observation group before and after treatment were significantly higher than those in the control group (
P
<
0.05
). In conclusion, the GPBDCT-based compression reconstruction algorithm has a better effect on MRI image processing, and edaravone can better remove free radicals and alleviate apoptosis.
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