Ligation Method Research Articles

Resveratrol alleviates acute lung injury through regulating PLSCR-3-mediated mitochondrial dysfunction and mitophagy in a cecal ligation and puncture model

Sepsis is considered as a life-threatening organ dysfunction caused by a dysregulated response of the host to an infection. Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life-threatening condition, and is the type of organ injury that is most commonly induced by sepsis. Resveratrol (RSV) has been shown to exert a wide range of therapeutic effects due to its anti-inflammatory and anti-oxidant properties. The present study aimed to investigate whether RSV could mitigate sepsis-induced ALI/ARDS, and also to unravel the underlying mechanism. The model of sepsis was established by applying the cecal ligation and puncture (CLP) method, and mitochondria from the lung tissue were isolated to assess mitochondrial function, as determined from measuring mitochondrial superoxide production using MitoSOX red mitochondrial superoxide indicator and the membrane potential. It was found that RSV could exert a protective role in CLP-induced ALI/ARDS, as evidenced by moderate levels of inflammatory cell infiltration and interstitial edema, as well as decreased levels of C-reactive protein (P<0.01), interleukin (IL)-6 (P<0.01), IL-1β (P<0.01) and tumor necrosis factor-α (P<0.01). Moreover, phospholipid scramblase 3 (PLSCR-3)-mediated mitochondrial dysfunction and mitophagy were shown to contribute towards the CLP-caused lung damage, which was reversed upon RSV administration, as demonstrated by improved mitochondrial function and markedly reduced increases in the protein levels of autophagy related (ATG)5 (P<0.01), ATG7 (P<0.05) and microtubule-associated protein 1A/1B-light chain 3 (LC3-Ⅰ/Ⅱ) (P<0.01), and a significantly increased expression of P62 (P<0.05). In addition, with regard to the CLP-induced lung injury in the mouse model, overexpression of PLSCR-3 was found to remove the beneficial effects observed upon RSV treatment. Taken together, the results of the present study have uncovered a novel molecular mechanism through which RSV may alleviate ALI/ARDS via regulating PLSCR-3-mediated mitochondrial dysfunction and mitophagy in CLP-induced mouse model.

Surgical left atrial appendage closure: success rate and its relationship with cerebrovascular accident

Background: Several surgical procedures such as excision or exclusion are recommended for the closure of the left atrial appendage (LAA). This study was conducted with the aim to evaluate the success rate of different surgical techniques for LAA closure, their respective complications, and the rate of post-surgical cerebrovascular accident (CVA). Methods: This retrospective study included 150 consecutive patients who underwent LAA closure most commonly after mitral valve surgery within 3 to 6 months after surgery. An expert echocardiographic fellow collected the data on patients’ surgical LAA closure methods and history of CVA, types of prosthetic valves, mortality, and bleeding. Results: The failure rate for complete LAA closure was 36.7% (55 patients) in our study. The greatest success rate of complete LAA closure was seen in purse-string method (75.5%), followed by resection method (71.4%), while the lowest success rate (≈ 33.3%) was observed in ligation method. A significant relationship was observed between clots on the surface of metallic valve and postoperative CVA (P = 0.001; likelihood ratio: 32).In multivariate analysis, there was also no statistically significant relationship between partial LAA closure and the incidence of post-surgical CVA (P > 0.050). Conclusion: We observed the highest success rate of complete LAA closure in purse-string method followed by resection method. Interestingly, our results showed that despite the higher rate of residual LAA clot in cases of partial LAA closure, the occurrence of post-surgical CVA was mostly related to the presence of clots on the surface of metallic mitral prostheses rather than the presence of partial LAA closure.

Gallic Acid Improved Amytryptiline Effect in Neuropathic Pain Induced by Partial Sciatic Nerve Ligation (PSNL) in Rats

Aim and Backround: Amytriptiline (AMY), an antidepressant, is used in the treatment of neuropathic pain. However, with limited therapeutic benefits and side effects of AMY, it is not helpful to the majority of the neuropathic pain patients. Gallic acid (GA) is a polyphenolic product with potential antioxidant effects, useful in neuropathic pain. Objective: The purpose of the study was to investigate the improved neuropathic pain relief with GA in combination with AMY in rats. Methods: Partial sciatic nerve ligation (PSNL) method is used for neuropathic pain induction in rats. The rats were randomly divided into 6 groups (n = 8), and treated with drugs or vehicle once daily for 15 days after the pain induction. The first group served as Normal control and received normal saline (p.o), the second group served as Sham Control and received Normal Saline (p.o), the third group served as Surgery Control and received normal saline (p.o), the fourth group received AMY (25mg/kg, p.o), while the fifth group received GA (100mg/kg,p.o), and the sixth group received both AMY and GA. Further behavioural studies for pain were carried out on days 1,4,7,10,13,16,19 and 22. Histological studies of sciatic nerves were carried out on days 1, 15 and 22, and on the 22nd day, all the remaining animals were sacrificed for the biochemical estimations of the sciatic nerve tissues. Results: GA attenuates neuropathic pain better in combination with AMY by ameliorating the behavioral, biochemical and histopathological signs and symptoms. This resultant effect is due to its antioxidant, antinociceptive and anti-inflammatory actions. It also potentiates AMY antinociceptive and antioxidant effects when given in combination in a continuous treatment. Conclusion: The results suggest that GA in combination with AMYattenuated the neuropathic pain. Hence, the use of GA as an adjunctive with AMY in the neuropathic pain will be more therapeutically beneficial; further studies on patients to confirm the results are warranted.

Thrombolytic Effect of Nattokinase and Its Mechanism

Objective: Exploring the anti-thrombotic effect and mechanism of nattokinase in vitro and vivo. Methods: The thrombolytic effect of NK on old thrombus was studied by blood clot lysis method in vitro, the rat carotid artery thrombosis model induced by ferric chloride and the rat venous thrombosis model induced by inferior vena cava ligation method were used to study the thrombolytic effect of NK in vivo. TXB2, 6-k, PGE2, t-PA, \begin{document}$\cdot {\rm{O}}_2^- $\end{document} , ·OH, XOD and other indicators were detected to explore the antithrombotic mechanism of NK. Results: Nattokinase could significantly dissolve old thrombus (P \begin{document}$\cdot {\rm{O}}_2^- $\end{document} , ·OH and XOD. The values of TXB2, PEG2, \begin{document}$\cdot {\rm{O}}_2^- $\end{document} , ·OH and XOD were increased significantly, while the values of 6-K-PGF1 α and t-PA were decreased significantly. Conclusion : NK had strong thrombolytic activity in vivo and vitro, and had effect on fresh thrombus and old thrombus. NK could inhibit thrombosis by inhibiting platelet aggregation, reduce oxidative damage and reducing the level of coagulation factors. NK could also play a direct thrombolytic role by stimulating the production of t-PA, dissolving fibrin, and might play an indirect thrombolytic role by inhibiting the production of PAI-1.

Conjugation of a Blood Brain Barrier Peptide Shuttle to an Fc Domain for Brain Delivery of Therapeutic Biomolecules.

The frequency of brain disease has increased significantly in the past years. After diagnosis, therapeutic options are usually limited, which demands the development of innovative therapeutic strategies. The use of antibody–drug conjugates (ADCs) is promising but highly limited by the existence of the blood–brain barrier (BBB). To overcome the impermeability of this barrier, antibody fragments can be engineered and conjugated to BBB peptide shuttles (BBBpS), which are capable of brain penetration. Herein, we linked the highly efficient BBBpS, PepH3, to the IgG fragment crystallizable (Fc) domain using the streamlined expressed protein ligation (SEPL) method. With this strategy, we obtained an Fc-PepH3 scaffold that can carry different payloads. Fc-PepH3 was shown to be nontoxic, capable of crossing an in vitro cellular BBB model, and able to bind to the neonatal Fc receptor (FcRn), which is responsible for antibody long half-life (t1/2). Overall, we demonstrated the potential of Fc-PepH3 as a versatile platform readily adaptable to diverse drugs of therapeutic value to treat different brain conditions.

Early soft tissue response to zirconium oxide and titanium healing abutments in vivo: a study in dogs

BackgroundThis study aimed to investigate the clinical characteristics and early soft tissue response to zirconium oxide (Zr) and titanium (Ti) healing abutments in dogs.MethodsEight implants (four at each hemi-mandible) were inserted after bilateral mandibular third and fourth premolars and first molar extraction in dogs. Then, two Zr and two Ti healing abutments were connected to each unilateral mandible eight weeks later. The ligation method was used to create a peri-implant mucositis model and the 24 abutments were divided into four groups: Zr or Ti healing abutments with ligation (ZrL, TiL) or non-ligation (ZrN, TiN). The clinical indices, peri-implant crevicular fluid (PICF), and inflammatory cytokines (TNF-α and IL-1β) were measured and analyzed on days 0 and 28. The dogs were then sacrificed on day 28, soft tissues around the implants were harvested, and inflammation infiltration was tested by immunohistochemistry. Normal distribution test and two-way analysis of variance was used to analyze the data.ResultsThe results showed that the clinical indices were similar for Zr and Ti healing abutments. There was significantly more PICF in the ZrL and TiL groups compared to in the ZrN and TiN groups. The TNF-α levels in PICF were significantly different between ZrL and ZrN groups on day 28. And the TNF-α levels in PICF were significantly higher in TiL group on day 28 than that on day 0. However, the number of inflammatory cells was not significantly different between the groups as measured by immunohistochemistry.ConclusionsThese data indicate that soft tissue responses to Zr healing abutments with peri-implant mucositis were comparable to those of Ti healing abutments in vivo, providing a theoretical foundation for the clinical application of Zr abutments.

Clinical value and role of microRNA-29c-3p in sepsis-induced inflammation and cardiac dysfunction

BackgroundThe goal of this study was to investigate the diagnostic value of miR-29c-3p in sepsis and its role in sepsis-induced inflammatory response and cardiac dysfunction.MethodsSerum level of miR-29c-3p was detected by qRT-PCR. The ROC curve was used to evaluate the diagnostic value of miR-29c-3p for Sepsis. The cecal ligation and puncture method (CLP) was used to establish a rat sepsis model. To assess cardiac function, left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and maximum rate of rise/fall of left ventricle pressure (± dp/dtmax) in different experimental groups were detected, and the serum cardiac troponin I (cTnI), creative kinase isoenzyme MB (CK-MB) were measured by ELISA. Meanwhile, TNF-α, IL-1β, and IL-6 were detected by ELISA to assess the level of inflammatory response in animals.ResultsmiR-29c-3p level was upregulated in sepsis patients. ROC curve revealed that miR-29c-3p had the ability to distinguish sepsis patients from healthy controls. Cardiac dysfunction and inflammation were observed in sepsis rat, which were characterized by the decrease of LVSP and + dp/dtmax, the increase of LVEDP, − dp/dtmax, cTnI, CK-MB, TNF-α, IL-1β, IL-6. All effects were reversed by the injection of miR-29c-3p antagomir. Logistics regression analysis manifested miR-29c-3p is an independent factor in the occurrence of cardiac dysfunction in sepsis patients.ConclusionsmiR-29c-3p has potential as a biomarker for the diagnosis of sepsis, and inhibition of miR-29c-3p expression in animal models reduced sepsis-induced cardiac dysfunction and inflammatory response.

Beneficial effects and related mechanism of hawthorn leaves flavonoids on cardiac function in rats with acute myocardial infarction

Objective: To explore the effect and related regulatory mechanism of hawthorn leaf flavonoids (FHL) on cardiac function in rats with acute myocardial infarction (AMI). Methods: Sixty SPF male Sprague-Dawley rats (9-week-old, weighing 300-350 g) were used in this study. Ten rats were assigned to sham operation group, and the remaining 50 rats were used to establish the AMI model with coronary artery ligation method, AMI was successfully established in 36 rats. AMI rats were randomly divided into AMI group and FHL low-, medium-, and high-dose groups (n=9 for each group). Rats received intraperitoneal injection (10 ml·kg-1·day-1) with physiological saline and FHL solution with concentrations of 0.3, 0.6, and 1.2 mg/ml, respectively for 4 consecutive weeks. Echocardiography was performed at the end of experiments. Left ventricular end diastolic diameter (LVEDD), left ventricular end diastolic anterior wall thickness (LAWD), left ventricular ejection fraction (LVEF) and left ventricular end diastolic pressure (LVEDP) were measured. Then the rats were sacrificed under deep anesthesia, and the left ventricular anterior wall tissue was used for pathological examinations by hematoxylin-eosin (HE) staining. Other myocardial tissue was used for in situ terminal transferase labeling (TUNEL) staining, and the apoptosis rate of cardiomyocytes was calculated. The myocardial cell apoptosis rate, the mRNA, and protein expressions of phosphatidylinositol 3β-kinase (PI3K), protein kinase B (Akt), glycogen synthetase kinase-3 (GSK3β), cyclin D1 and the protein expressions of p-Akt and p-GSK3β were detected by real-time fluorescent quantitative PCR (RT-qPCR) and Western blot respectively. Results: Compared with sham operation group, the LVEDD and LVEDP of the rats in AMI group and FHL low-, medium-and high-dose groups were increased, and the LAWD and LVEF were reduced (all P<0.05). Compared with AMI group, LVEDD and LVEDP were reduced, and LAWD and LVEF were increased in FHL low-, medium-and high-dose groups (all P<0.05). LVEDD and LVEDP decreased, and LAWD and LVEF increased in proportion to the increase of FHL dose (all P<0.05). LVEDD and LAWD values were similar between FHL low-dose and medium-dose groups (both P>0.05). HE staining results evidenced necrotic myocardial tissue, together with disordered arrangement of myocardial fibers, and a large number of inflammatory cells infiltrated in the myocardial tissue in AMI group. The myocardial damage of rats in FHL low-, medium-, and high-dose groups was less than that of AMI group. The myocardial fibers were arranged neatly, but there were still partial breaks and a small amount of inflammatory cell infiltration in the myocardial tissue and there were scattered islands of normal myocardial tissue in the infarct area of these groups. Among them, myocardial damage was the least in FHL high-dose group. The results of TUNEL staining showed that compared with AMI group, the apoptosis rate of myocardial cells was significantly reduced in FHL low-, medium-, and high-dose groups (all P<0.001), but was still higher than that in sham operation group (all P<0.001). Myocardial cell apoptosis rate decreased in proportion with increasing FHL dose (P<0.05). The RT-qPCR results showed that compared with AMI group, the expression levels of PI3K and cyclin D1 mRNA were significantly upregulated in the myocardial tissue of rats in FHL low-, medium-, and high-dose groups, but still lower than those in sham operation group (all P<0.05), and PI3K and cyclin D1 mRNA expression levels increased with the increase dose of FHL (P<0.05). Western blot results showed that compared with AMI group, the expression levels of PI3K, p-Akt, p-GSK3β, and cyclin D1 were significantly upregulated in the myocardial tissue of rats in FHL low-, medium-, and high-dose groups, but still lower than those in sham operation group (all P<0.05), and the protein expression levels of PI3K, p-Akt, p-GSK3β, and cyclin D1 increased in proportion with the increase dose of FHL (all P<0.05). Conclusion: FHL can effectively improve cardiac function in rats with AMI, and the beneficial effects may be partly mediated through activating PI3K/GSK3β/cyclin D1 signaling pathway.

Acetazolamide Alleviate Cerebral Edema Induced by Ischemic Stroke Through Inhibiting the Expression of AQP4 mRNA.

We want to investigate the effect of aquaporin-4 (AQP4) on cerebral edema induced by ischemic stroke in rats and explore whether inhibiting the expression of AQP4 through acetazolamide (AZA) could attenuate brain edema and protect cerebral function. The Sprague Dawley (SD) rats were randomly divided into four groups: sham + saline group, sham + AZA group, AZA intervention group, and nonintervention group. Each group was divided into five subgroups according to the time of cerebral ischemia (6h, 1day, 3days, 5days, and 7days). The model of cerebral infarction in rats was adopted by means of the bilateral carotid arteries ligation (2-VO) method. The rats inintervention group were given intraperitoneal injection of AZA (35mg/kg/day). Hematoxylin-eosin staining was performed for pathological analysis of the infarcted area. The brain water content was calculated to evaluate the degree of brain edema. The messenger RNA (mRNA) and protein expressions of AQP4 in the brain were measured by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. Significant cerebral pathological damages were found in ischemic stroke rats. The brain water content, protein, and mRNA expression of AQP4 of the intervention and nonintervention groups were markedly higher than those of the sham groups. By contrast, AZA administration reduced the brain water content, whereas improved cerebral dysfunction was induced by ischemic stroke. Moreover, AZA obviously reduced the protein and mRNA expression of AQP4 after ischemic stroke in rats' brains. The expression of AQP4 was closely related to cerebral edema induced by ischemic stroke. Decreasing the expression of AQP4 mRNA by AZA administration can effectively relieve cerebral edema and decrease cerebral pathological damage.

Antiulcerogenic activity of Yttrium and Copper oxide nanoparticles

Gastric ulcer is an excavation of mucosa and extending to submucosal layers due to increased gastric secretion, generation of free radicals and imbalance between protective factors and aggravating factors. The present study aimed to screen yttrium and copper oxide nanoparticles for antiulcerogenic activity. Metal oxide nanoparticles were evaluated for various biological activities considering their high surface area to volume ratio, different oxidative states, cell permeability etc. Various studies have proved metal oxide nanoparticles to be beneficial in various ailments due to their antioxidant, antibacterial, and other pharmacological activities. Nanoparticles prepared using biogenic methods were relatively more biocompatible and less toxic compared to conventional methods of synthesis. In the present study, green synthesized yttrium and copper oxide nanoparticles were evaluated for acute toxicity, antioxidant, proton pump inhibition and antiulcerogenic activity. In vitro antioxidant activity by DPPH, nitric oxide scavenging methods and H+K+ATPase assay was performed to evaluate the mechanism of action. Synthesized nanoparticles have shown no signs of acute toxicity as per OECD 423. Pyloric ligation method was performed to evaluate gastric volume, pH and ulcer severity. The present study revealed the dose-dependent antiulcer potential of yttrium oxide nanoparticles at doses of 2mg/kg and 20mg/kg. Antisecretory action of yttrium and copper oxides were evident from in vitro H+K+ATPase activity and inhibition of gastric volume. Antioxidant activities of yttrium oxide nanoparticles indicate gastric mucosal protection by free radical scavenging action. Copper oxide nanoparticles produced antisecretory activity but produced mucosal damage and hemorrhage at a dose of 20mg/kg.

The effect of ligation methods on biofilm formation in patients undergoing multi-bracketed fixed orthodontic therapy - A systematic review.

Many modifications to fixed orthodontic appliances have been introduced to manage biofilm formation. The aim of this review was to investigate elastomeric ligation in comparison with stainless steel ligation and self-ligation with regard to microbiological and clinical indicators of biofilm formation in patients wearing multi-bracketed fixed orthodontic appliances. The MEDLINE and the EMBASE databases were searched up to February 2021 and supplemented by additional manual searches of bibliographies. Parallel-group and split-mouth randomized controlled trials (RCTs) comparing different ligation methods were identified. The Cochrane Risk of Bias-2 tool was applied to assess the quality of evidence. A total of 11 RCTs were included in this review. Nine RCTs compared self-ligation and elastomeric ligation; two compared elastomeric ligation and stainless steel ligation. The included studies had either some concerns or were at a high risk of bias. Qualitative assessment of the studies identified that there were no significant differences in biofilm formation between elastomeric ligation and self-ligation, but that stainless steel ligation was less susceptible to biofilm formation than elastomeric ligation. There were no significant differences between self-ligation and elastomeric ligation for biofilm formation in patients wearing multi-bracketed fixed orthodontic appliances. Stainless steel ligation may accumulate less biofilm than elastomeric ligation; however, the clinical significance of the difference could not be evaluated. Further high-quality studies are required in order to determine which ligation method is better for managing biofilm formation in patients wearing multi-bracketed fixed orthodontic appliances.

PH-Controlled Protein Orthogonal Ligation Using Asparaginyl Peptide Ligases.

Peptide asparaginyl ligases (PALs) catalyze transpeptidation at the Asn residue of a short Asn-Xaa1-Xaa2 tripeptide motif. Due to their high catalytic activity toward the P1-Asn substrates at around neutral pH, PALs have been used extensively for peptide ligation at asparaginyl junctions. PALs also bind to aspartyl substrates, but only when the γCOOH of P1-Asp remains in its neutral, protonated form, which usually requires an acidic pH. However, this limits the availability of the amine nucleophile and, consequently, the ligation efficiency at aspartyl junctions. Because of this perceived inefficiency, the use of PALs for Asp-specific ligation remains largely unexplored. We found that PAL enzymes, such as VyPAL2, display appreciable catalytic activities toward P1-Asp substrates at pH 4-5, which are at least 2 orders of magnitude higher than that of sortase A, making them practically useful for both intra- and intermolecular ligations. This also allows sequential ligations, first at Asp and then at Asn junctions, because the newly formed aspartyl peptide bond is resistant to the ligase at the pH used for asparaginyl ligation in the second step. Using this pH-controlled orthogonal ligation method, we dually labeled truncated sfGFP with a cancer-targeting peptide and a doxorubicin derivative at the respective N- and C-terminal ends in the N-to-C direction. In addition, a fluorescein tag and doxorubicin derivative were tagged to an EGFR-targeting affibody in the C-to-N direction. This study shows that the pH-dependent catalytic activity of PAL enzymes can be exploited to prepare multifunction protein biologics for pharmacological applications.

Down-regulation of SNHG16 alleviates the acute lung injury in sepsis rats through miR-128-3p/HMGB3 axis

BackgroundLong noncoding RNAs contribute to various inflammatory diseases, including sepsis. We explore the role of small nucleolar RNA host gene 16 (SNHG16) in sepsis-mediated acute lung injury (ALI) and inflammation.MethodsA sepsis-induced ALI rat model was constructed by the cecal ligation and perforation method. The profiles of SNHG16, miR-128-3p, and high-mobility group box 3 (HMGB3) were monitored by quantitative reverse transcription PCR and Western blot. The pathologic changes of lung tissues were evaluated by Hematoxylin–Eosin staining, immunohistochemistry, and dry and wet method. Meanwhile, the pro-inflammatory factors and proteins were determined by ELISA and Western blot. In contrast, a sepsis model in BEAS-2B was induced with lipopolysaccharide (LPS) to verify the effects of SNHG16/miR-128-3p/HMGB3 on lung epithelial cell viability and apoptosis.ResultsAs a result, SNHG16 and HMGB3 were up-regulated, while miR-128-3p was down-regulated in sepsis-induced ALI both in vivo and in vitro. Inhibiting SNHG16 reduced the apoptosis and inflammation in the sepsis-induced ALI model. Overexpressing SNHG16 promoted LPS-mediated lung epithelial apoptosis and inhibited cell viability and inflammation, while miR-128-3p had the opposite effects. Mechanistically, SNHG16 targeted miR-128-3p and attenuated its expression, while miR-128-3p targeted the 3′ untranslated region of HMGB3.ConclusionsOverall, down-regulating SNHG16 alleviated the sepsis-mediated ALI by regulating miR-128-3p/HMGB3.

Effect of hypogastric artery ligation in obstetric hemorrhage and fertility

Aim: In this study, we aimed to examine the effectiveness of hypogastric artery ligation method in obstetric hemorrhage and its effects on fertility.&#x0D; Patients and Methods: Sixty-two patients who underwent bilateral hypogastric artery ligation (HAL) due to obstetric bleeding at Kocaeli Derince Training and Research Hospital between November 1, 2011 and November 1, 2016 were retrospectively evaluated.&#x0D; Results: In patients with postpartum hemorrhage, bleeding was controlled with HAL in 47 (84%) of them, while hysterectomy was performed in addition to HAL in 9 (16%) patients. While 17 patients gave consent for bilateral tubal ligation before the operation, none were in the hysterectomy group. Postoperative follow-up information was obtained for 31 of the remaining 36 patients. It was observed that 7 of the patients had an intrauterine device inserted, 3 gave birth in our center, 18 had regular menstrual periods, and 3 had hysteroscopy due to irregular menstrual periods, which revealed no pathology.&#x0D; Conclusion: HAL is an important procedure used as the last step in obstetric bleeding, especially in fertility-sparing surgery, and it can be used safely by experienced surgeons. More emphasis should be placed on this surgical method in today's gynecology and obstetrics residency training process.

Zinc‑finger E‑box‑binding homeobox 1 alleviates acute kidney injury by activating autophagy and the AMPK/mTOR pathway.

Zinc‑finger E‑box‑binding homeobox1(ZEB1) is involved in epithelial‑mesenchymal transition. In the present study, the protective effect of ZEB1 on acute kidney injury (AKI) was explored. The cecal ligation and puncture(CLP) method was performed to establish the AKI model in rats. ZEB1 expression, blood urea nitrogen(BUN) and serum creatinine (SCr) levels, inflammation [interleukin(IL)‑1β, IL‑6, and tumour necrosis factor‑α], phosphorylated AMP‑activated protein kinase (p‑AMPK) and phosphorylated mammalian target of rapamycin (p‑mTOR) expression, and histopathological changes in CLP‑induced AKI rats were assessed. AMPK inhibitor dorsomorphin(DM) was intraperitoneally injected to determine the effect of ZEB1 on AKI and the regulatory mechanism involving the AMPK/mTOR pathway. CLP downregulated ZEB1 expression, increased BUN and SCr levels, promoted inflammation and apoptosis, and increased the acute kidney score in the kidney tissues of CLP‑induced AKI rats. Autophagy and the AMPK/mTOR pathway were blocked in CLP‑induced AKI rats. ZEB1 overexpression inhibited inflammation and apoptosis, reduced BUN and SCr levels, and activated autophagy and the AMPK/mTOR pathway in CLP‑induced AKI rats. The protective effect of ZEB1 overexpression on AKI was reversed by DM. Thus, ZEB1 was revealed to alleviate CLP‑induced AKI by activating autophagy and the AMPK/mTOR pathway.

F-18 FDG PET/CT CAN BE USED AS AN IMAGING BIOMARKER FOR REFLECTING SYNTHETIC VASCULAR SMOOTH MUSCLE CELL ACTIVITY IN THE ANIMAL MODEL OF VASCULAR REMODELING DISORDER

Objective: Synthetic vascular smooth muscle cells (VSMCs) play important roles in vascular remodeling disorders including atherosclerosis, restenosis, and transplant vasculopathy. 18F-fluorodeoxyglucose positron emission tomography (F-18 FDG PET/CT) is a non-invasive molecular imaging modality widely used in clinical practice for reflecting glucose metabolism. The aim of this study was to demonstrate the feasibility of measuring the activity of synthetic VSMCs using F-18 FDG PET/CT in an atherosclerotic rat model of partial carotid artery ligation. Design and method: Using Sprague-Dawley rats, neointimal hyperplasia was made by right partial carotid ligation method. After 1 month, all animal models undertook F-18 FDG PET/CT images. Then the vessels were harvested and analyzed with autoradiography and histomolecular approaches. Results: The affected carotid artery exhibited prominent neointinal hyperplasia region with a narrowed lumen. Known surrogate marker of synthetic VSMCs including matrix metallopeptidase-9, cyclophilin A, and collagen type III were increased in neointimal hyperplasia region. There were no immune cells such as macrophages or neutrophils. F-18 FDG PET/CT and autoradiography showed increased tracer uptake along the same affected arteries. Glucose transporter-1 was also increased in neointimal hyperplasia region. Conclusions: It is feasible to use F-18 FDG PET/CT as an imaging surrogate-marker for reflecting synthetic VSMC activities in vascular remodeling disorders.

Superior Laryngeal Nerve Injury in Thyroidectomy Surgery

Introduction: The thyroid gland is one of the endocrine glands with the most frequent disorders or diseasescompared to other endocrine glands. Treatment of these disorders is generally performed by surgery orcalled a thyroidectomy. Thyroidectomy surgery can pose a risk of complications, both early complications,and late complications. Common complications are hemorrhage, hypoparathyroidism, recurrent laryngealnerve injury, and external branch of the superior laryngeal nerve.Purpose: To analyze the effect of the surgical method of superior thyroideal vasa ligation as distally aspossible on the prevention of injury to the external branch of the superior laryngeal nerve (EBSLN) inthyroidectomy.Methods: Clinical trial study with pre and post-test design in patients undergoing thyroidectomy surgery.Patients were examined using a questionnaire of the injury-related voice of EBSLN (SKC-EBSLN), whichtested the validity and reliability of the previous test and measured 1-octave sound ability before and afterthyroidectomy surgery using the superior thyroidectomy vasa ligation method as distally as possible to seeits effect on EBLSN function and tone ability function.Results: There were differences in the scores of the SKC-EBSLN questionnaire before and afterthyroidectomy surgery using the method of superior thyroideal vasa ligation as distally as possible (p&lt;0.05). Further analysis showed that clinical diagnosis, surgery, tumor size, and AP outcome did not havea statistically significant effect on the postoperative SKC-EBSLN score (p&gt; 0.05). In this study, the SKCEBSLN score had a significant effect on the 1-octave tone ability (p &lt;0.05).Conclusion: As many as 51.9% of patients had a normal voice condition with few complaints and wereable to sing 1-octave tone after surgery using the method of superior thyroidal vasa ligation as distally aspossible. The SKC-EBSLN questionnaire is a valid and reliable questionnaire to evaluate the results ofthyroidectomy surgery.

Exploring the regulatory mechanism of Nao Tai Fang on vascular Dementia's biological network based on cheminformatics and transcriptomics strategy

Ethnopharmacological relevanceNao Tai Fang (NTF) is modified from Buyang Huanwu Decoction. Modern pharmacological research showed that NTF has a good anti-cerebral ischemic effect and can improve the learning and memory ability of cerebrovascular disease. AimThe purpose of this study is to explore the regulation mechanism of NTF on the regulation mechanism of vascular dementia (VD)'s biological network based on chemoinformatics and transcriptomics strategies. MethodFirst, the bilateral common carotid artery ligation method was used to create a rat VD model. After NTF intervention for 30 days, the treatment effect was evaluated by HE staining and water maze experiment. Then, the Agilent mRNA expression profiling chip was used to obtain mRNA expression data of hippocampal tissues of VD model rats before and after NTF intervention, and microarray analysis was used to screen for genes with significant differential expression. The BATMAN database was utilized to obtain the potential targets of NTF and the Genecards and OMIM were utilized to collect the VD potential genes. The cytoscape was utilized to construct and analyze the networks. ResultThe animal experiments showed that NTF can improve VD. A total of 180 up-regulated proteins and 289 down-regulated proteins were identified. The top 20 up- and down-regulated differentially expressed genes were utilized to construct differentially expressed gene's protein-protein interaction (PPI) network. A total of 677 NTF potential targets and 550 VD genes were obtained and were utilized to construct NTF-VD PPI network. The cheminformatics analysis showed that NTF can regulate a lot of biological processes and signaling pathways (such as inflammation modules, vasodilation and contraction modules, hypoxia modules, angiogenesis, coagulation, neurovascular unit modules, Neuroactive ligand-receptor interaction, Calcium signaling pathway, Serotonergic synapse). ConclusionNTF may play a role in the treatment of VD through the targets, signaling pathways and biological processes discovered in this study.

Rationality and necessity of vascular stapler application during liver resection (Review).

Liver resection (LR) is the primary treatment method for patients with hepatocellular carcinoma (HCC). Improving surgical safety and reducing surgical morbidity and mortality is important for patients receiving LR. Various devices have been developed to facilitate vascular transection to reduce intraoperative blood loss, which is considered to be a predictor of poor surgical outcomes in patients undergoing LR. Vascular staplers have been widely applied for the division of major vascular and biliary structures in the process of LR; however, when and how to use these tools remains controversial. This review aims to report the rationality and necessity of using vascular staplers in vessel transection during liver surgery. Due to the risk of intraoperative and postoperative hemorrhage and biliary fistula, the process of transection of the portal pedicle and hepatic vein is a crucial step during LR. Stapling represents a vascular dissection technique that is widely used in laparoscopic LR and has then been popularized in open LR. Advocates argue that stapler transection methods provide several advantages, including diminished blood loss, fewer transfusion requirements and shorter operative times. However, other studies have failed to demonstrate those benefits when using these tools compared with the simple clamp-crushing technique. Using the stapler vascular transection method resulted in smaller surgical margins and similar surgical outcomes compared with those of the clamp-crushing vascular transection method. However, the intraoperative use of vascular staplers may significantly increase the financial burden of liver resection for patients with HCC, while not improving short- and long-term outcomes. Therefore, it has been suggested that vascular staplers should not be routinely used in LR. The current review discussed the above points and recommended that the stapling transection of the portal pedicle and hepatic vein should be applied during laparoscopic LR in a rational manner. However, the suturing ligation method should be routinely used in open LR.

ALS/FTD-causing mutation in cyclin F causes the dysregulation of SFPQ.

Previously, we identified missense mutations in CCNF that are causative of familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Hallmark features of these diseases include the build-up of insoluble protein aggregates as well as the mislocalization of proteins such as transactive response DNA binding protein 43 kDa (TDP-43). In recent years, the dysregulation of SFPQ (splicing factor proline and glutamine rich) has also emerged as a pathological hallmark of ALS/FTD. CCNF encodes for the protein cyclin F, a substrate recognition component of an E3 ubiquitin ligase. We have previously shown that ALS/FTD-linked mutations in CCNF cause disruptions to overall protein homeostasis that leads to a build-up of K48-linked ubiquitylated proteins as well as defects in autophagic machinery. To investigate further processes that may be affected by cyclin F, we used a protein-proximity ligation method, known as Biotin Identification (BioID), standard immunoprecipitations and mass spectrometry to identify novel interaction partners of cyclin F and infer further process that may be affected by the ALS/FTD-causing mutation. Results demonstrate that cyclin F closely associates with proteins involved with RNA metabolism as well as a number of RNA-binding proteins previously linked to ALS/FTD, including SFPQ. Notably, the overexpression of cyclin F(S621G) led to the aggregation and altered subcellular distribution of SFPQ in human embryonic kidney (HEK293) cells, while leading to altered degradation in primary neurons. Overall, our data links ALS/FTD-causing mutations in CCNF to converging pathological features of ALS/FTD and provides a link between defective protein degradation systems and the pathological accumulation of a protein involved in RNA processing and metabolism.