Circular RNA hsa_circ_0012673 facilitates lung cancer cell proliferation and invasion via miR-320a/LIMK18521 axis.

OBJECTIVE: Lung cancer is one of the most malignant tumors with high morbidity and mortality in the world. The incidence and mortality of lung cancer were increased per year in many countries over the past 50 years. The increasing studies had shown that circular RNA (circRNA) was involved in the progression of lung cancer. Therefore, it was significant to seek the molecular mechanism of circ_0012673 in lung cancer. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to estimate the expression levels of circ_0012673, miR-320a and LIM domain kinase 1 (LIMK1) in lung cancer tissues and cells. 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT), flow cytometry and transwell assays were recruited to evaluate proliferation, apoptosis and mobility of lung cancer cells, respectively. The relative protein expression levels of Vimentin, N-cadherin, E-cadherin and LIMK1 were determined with Western blot assay. The relationships among circ_0012673, miR-320a and LIMK1 were analyzed by starBase database, dual-luciferase reporter assay, and Pearson's correlation. RESULTS: Circ_0012673 was overexpressed in lung cancer tissues and cell lines. Loss-of-functional experiment confirmed that knockdown of circ_0012673 constrained proliferation, motility and Epithelial-Mesenchymal Transition (EMT), but induced apoptosis by targeting miR-320a. Furthermore, LIMK1 was a target of miR-320a in lung cancer cells. Elevated LIMK1 could abolish the overexpression of miR-320a induced effects on lung cancer cells. Mechanistically, circ_0012673 contributed to lung cancer progression through mediating miR-320a /LIMK1 pathway. CONCLUSIONS: Circ_0012673 was a tumor-promoter in lung cancer via acting as competing endogenous RNA to regulate LIMK1 expression by binding miR-320a.

Time course of histomorphological changes in adipose tissue upon acute lipoatrophy.

BACKGROUND AND AIMS: Crown-like structures (CLS) are characteristic histopathology features of inflamed adipose tissues in obese mice and humans. In previous work, we suggested that these cells derived from macrophages primarily involved in the reabsorption of dead adipocytes. Here, we used a well-characterized transgenic mouse model in which the death of adipocytes in adult mice is inducible and highly synchronized. In this "FAT ATTAC" model, apoptosis is induced through forced dimerization of a caspase-8 fusion protein. METHODS AND RESULTS: 0, 0.5, 1, 2, 3 and 10 days post induction of adipocyte cell death, we analyzed mesenteric and epididymal adipose depots by histology, immunohistochemistry and electron microscopy. Upon induction of caspase-8 dimerization, numerous adipocytes lost immunoreactivity for perilipin, a marker for live adipocytes. In the same areas, we found adipocytes with hypertrophic mitochondria and signs of organelle degeneration. Neutrophils and lymphocytes were the main inflammatory cells present in the tissue, and the macrophages were predominantly Mac-2 negative. Over the course of ablation, Mac-2 positive macrophages substituted for Mac-2 negative macrophages, followed by CLS formation. All perilipin negative, dead adipocytes were surrounded by CLS structures. The time course of histopathology was similar in both fat pads studied, but occurred at earlier stages and was more gradual in mesenteric fat. CONCLUSION: Our data demonstrate that CLS formation results as a direct consequence of adipocyte death, and that infiltrating macrophages actively uptake remnant lipids of dead adipocytes. Upon induction of adipocyte apoptosis, inflammatory cells infiltrate adipose tissue initially consisting of neutrophils followed by macrophages that are involved in CLS formation.

Explaining Zipf's law via a mental lexicon.

Zipf's law is the major regularity of statistical linguistics that has served as a prototype for rank-frequency relations and scaling laws in natural sciences. Here we show that Zipf's law-together with its applicability for a single text and its generalizations to high and low frequencies including hapax legomena-can be derived from assuming that the words are drawn into the text with random probabilities. Their a priori density relates, via the Bayesian statistics, to the mental lexicon of the author who produced the text.

Dual modeling of political opinion networks.

We present the result of a dual modeling of opinion networks. The model complements the agent-based opinion models by attaching to the social agent (voters) network a political opinion (party) network having its own intrinsic mechanisms of evolution. These two subnetworks form a global network, which can be either isolated from, or dependent on, the external influence. Basically, the evolution of the agent network includes link adding and deleting, with the opinion changes influenced by social validation, the political climate, the attractivity of the parties, and the interaction between them. The opinion network is initially composed of numerous nodes representing opinions or parties that are located on a one dimensional axis according to their political positions. The mechanism of evolution includes union, splitting, change of position, and attractivity, taking into account the pairwise node interaction decaying with node distance in power law. The global evolution ends in a stable distribution of the social agents over a quasistable and fluctuating stationary number of remaining parties. Empirical study on the lifetime distribution of numerous parties and vote results is carried out to verify numerical results.

Clinical application of a patient-controlled apparatus for ventricular administration of morphine in intractable pain: report of 28 cases.

The authors developed a patient-controlled apparatus (L-224) for ventricular administration of pain-relieving medication and utilized it in the treatment of 28 patients with intractable pain. The initial dose of morphine hydrochloride was 1 mg, which afforded pain relief for an average of 170 hours. At an average dose of 1.8 mg, the average time of pain relief obtained was 137 hours. Therefore, they conclude that L-224 is a satisfactory apparatus for the ventricular administration of pain medication; it is patient controlled, safe, and reliable in clinical application.

[Cox regression model analysis of influence of the transitional mucosa adjacent to rectal carcinoma on anastomotic recurrence after anterior resection].

The influence of nine clinico-pathological factors on anastomotic recurrence of rectal cancer after anterior resection was analyzed using Cox regression model. Among the nine factors, the mucin histochemical changes in mucosa at the resection margins, Dukes' stage and histological type of the cancer were of significance (P less than 0.1). The most important variable for anastomotic recurrence was mucin histochemical changes at the resection margins according to the Wald statistic value. It is suggested that the transitional mucosa adjacent to rectal carcinoma in which mucin histochemical changes take place bears great weight on the further malignant transformation after anterior resection. The biological characteristics of the transitional mucosa and clinical significance of the application of Cox regression model for prognostic analysis are discussed.

Clinical and laboratory observations on polysaccharide sulphate (PSS) in 282 cases of ischemic cerebrovascular disease.

Polysaccharide sulphate (PSS) is a new heparinoid drug. The therapeutic effect and laboratory findings in the treatment of 282 cases with ischemic cerebrovascular disease by PSS were analysed in this study. In treating patients with acute cerebral infarction, the effective rate (93.2%) and highly effective rate (62.9%) were both significantly higher in comparison with controls. Excellent results were also obtained in treating patients with cerebral infarction at late and sequela stage and patients with transient ischemic attack. Laboratory observations and animal experiments showed that PSS has anticoagulative and vasodilatory effects. It can also reduce blood viscosity and serum lipids. So PSS is an effective drug for the prevention and treatment of ischemic cerebrovascular diseases.

The clinical and biological significance of the transitional mucosa adjacent to colorectal cancer.

The underlying nature of the transitional mucosa adjacent to colorectal cancer is defined and the evidence for and against the statement that this transitional mucosa involves primary premalignant change presented in this article. An association between mucin histochemical changes at the margins of resection and a poorer clinical outcome of patients has been recognized in patients with colorectal cancer after surgery. The retained transitional mucosa at the margins of resection appears to correlate with tumor recurrence and a poorer survival in patients who have undergone radical resection. It is considered that the transitional mucosa adjacent to colorectal cancer and its presence at the margins of resection may be an important prognostic marker for patients with large bowel cancer following radical resection.

Analgesia from electrical stimulation of the hypothalamic arcuate nucleus in pentobarbital-anesthetized rats.

Inhibition of noxious heat-induced tail flick by electrical stimulation of the arcuate nucleus of the hypothalamus (ARH) was examined and characterized in pentobarbital-anesthetized rats. Systematic mapping studies revealed that inhibition of the tail flick reflex could be induced by stimulating widespread areas in the ventromedial parts of the hypothalamus, which include the paraventricular nucleus, ventromedial nucleus, dorsomedial nucleus, anterior hypothalamic area as well as the ARH areas. The ARH stimulation-produced tail flick suppression could be completely blocked by systemic naloxone (2 mg/kg) which shows the involvement of an opiate mechanism in this effect. Although the tail flick reflex in the lightly anesthetized state is of significantly shorter latency than in the unanesthetized state, thresholds of the ARH stimulation for suppressing spinal nociceptive reflexes in the lightly anesthetized state were not significantly different from the thresholds at the same ARH sites in the awake state.

The role of periaqueductal gray in mediation of analgesia produced by different frequencies electroacupuncture stimulation in rats.

The marked suppression of noxious heat-evoked tail flick reflex was produced in conscious rats by low (2 Hz) or high (100 Hz) frequency electroacupuncture (EA) stimulation at acupoints S36 and Sp6. Electrolytic and kainate lesions in the ventral periaqueductal gray (vPAG) led to significant attenuation of the low and high frequency EA analgesia as measured 4 and 6 days following the lesion. In sham-operated animals, analgesia induced by either low or high frequency EA remained intact. The role of vPAG in organization of different EA analgesia is discussed in detail.

A GABAergic mechanism in the inhibition of cardiac vagal reflexes.

A depressor response and bradycardia were produced by aortic nerve stimulation in urethane-chloralose-anaesthetized, paralyzed and artificially ventilated rabbits. Stimulation of the superficial peroneal nerve (SP) or rostral ventrolateral medulla (rVLM) inhibited the aortic nerve stimulation-evoked bradycardia, which was also inhibited by direct microinjection of GABA into the dorsal vagus nucleus (DVN). Application of bicuculline methiodide into the same medullary area antagonized the effect of GABA and partially or completely abolished the SP or rVLM stimulation-produced inhibition. However, strychnine hydrochloride had no effect on the SP or rVLM stimulation-produced inhibition. These observations indicate that GABAergic system present at the DVN is possibly involved in the inhibition of evoked bradycardia during somatic afferent and rVLM stimulation.

The inhibitory effect of somatic inputs on the excitatory responses of vagal cardiomotor neurones to stimulation of the nucleus tractus solitarius in rabbits.

Experiments were done in 41 rabbits anaesthetized with urethane and chloralose, paralyzed with Flaxedil and ventilated artificially. Extracellular recordings of 142 units were made in the dorsal vagal nucleus (DVN) and the nucleus ambiguus (NA), identified by antidromic response to stimulation of the cervical vagus nerve. In total 63.5% of them exhibited spontaneous activity and 22 units (17 in DVN and 5 in NA) showed a cardiac rhythm; their antidromic conduction velocity was 3.7-12.5 m/s, which suggests their having axons in the range of B fibres. These neurones were classified as vagal cardiomotor neurones. A total of 16 DVN and 4 NA vagal cardiomotor neurones were excited orthodromically by electrical stimulation of the contralateral nucleus tractus solitarius (NTS). Electrical stimulation of the superficial peroneal nerve (SP) with low intensity or the deep peroneal nerve (DP) with high intensity which activated C fibres inhibited excitatory responses of 16 neurones (14 in DVN and 2 in NA). The other 4 neurones were unaffected by SP inputs. These results provide electrophysiological evidence for the inhibitory effect of somatic inputs on the evoked discharges of vagal cardiomotor neurones in the DVN and the NA.