Tinospora Cordifolia and Arabinogalactan in combination modulates benzo(a)pyrene-induced genotoxicity during lung carcinogenesis.

The present study explored the effects of combination of Tinospora cordifolia and Arabinogalactan on surface membrane dynamics and programmed cell deaths in rat model of lung cancer. The rats were divided into different groups namely normal control, benzo(a)pyrene (BP) treated, BP + Tinospora cordifolia (TC)-treated, BP + Arabinogalactan (A)-treated and BP + TC + A-treated groups. Significant changes were observed in the membrane dynamics of rats treated with BP. The carcinogen treatment demonstrated a marked decrease in membrane microviscosity. Also, excimer/monomer ratio and fluidity parameters of BP treated rats showed significant rise. On the other hand, combination of Tinospora cordifolia and Arabinogalactan improvised surface membrane dynamics. Moreover, micronuclei formation along with protein expression of bcl-2 showed significant increase in the lungs of BP treated rats. The combined treatment of Tinospora cordifolia and Arabinogalactan moderated the micronuclei formation in BP treated rats. Also, the combined treatment regulated the protein expressions of bcl-2 in BP-treated rats. As a result, marked improvement was noticed in apoptosis of BP treated cells treated with combination treatment. This study concludes that the Tinospora cordifolia and Arabinogalactan in combination improve the surface membrane dynamics and apoptosis in BP-treated rats.

CXCR2 is involved in pulmonary intravascular macrophage accumulation and angiogenesis in a rat model of hepatopulmonary syndrome.

Hepatopulmonary syndrome (HPS) is a lung complication in various liver diseases, with high incidence, poor prognosis and no effective non-surgical treatments in patients with hepatocirrhosis. Therefore, assessing HPS pathogenesis to explore proper therapy strategies is clinically relevant. In the present study, male Sprague-Dawley rats underwent sham operation or common bile duct ligation (CBDL). Two weeks post-surgery, the following groups were set up for 2 weeks of treatment: sham + normal saline, CBDL + CXCR2 antagonist SB225002, CBDL + tumour necrosis factor α (TNF-α) antagonist PTX and CBDL + normal saline groups. Liver and lung tissues were collected after mean arterial pressure (MAP) and portal venous pressure (PVP) measurements. Haematoxylin and eosin (H&E) staining (lung) and Masson staining (liver) were performed for pathological analyses. Finally, pulmonary tissue RNA and total protein were assessed for target effectors. The mRNA and protein levels of CXCR2 were significantly increased in the pulmonary tissue of CBDL rats. What's more, CXCR2 inhibition by SB225002 reduced the expression of CD68 and von Willebrand factor (vWf) in CBDL rats. Importantly, CXCR2 inhibition suppressed the activation of Akt and extracellular signal-regulated kinase (ERK) in CBDL rats. Antagonization of TNF-α with PTX down-regulated the expression of CXCR2. During HPS pathogenesis in rats, CXCR2 might be involved in the accumulation of pulmonary intravascular macrophages and angiogenesis, possibly by activating Akt and ERK, with additional regulation by TNF-α that enhanced pulmonary angiogenesis by directly acting on the pulmonary tissue. Finally, the present study may provide novel targets for the treatment of HPS.

[Expression of interferon-induced protein with tetratricopetide repeats 1 and liver cell apoptosis in mice with severe burns].

OBJECTIVE: To explore the relationship between the expression of interferon-induced protein with tetratricopetide repeats 1 (IFIT1) and liver cell apoptosis in the acute stress period after severe burns.
 METHODS: A total of 25 C57/129 adult mice were randomly divided into the normal control group (0 h) and the groups at 1, 6, 12 or 24 after severe burns (n=5 per group). A model with third degree (20% of the total body surface area) burn injury was established and then liver tissues were taken. IFIT1 expression was examined by Western blot. The expression of caspase-3 and -8 was measured by immunohistochemistry. Liver cell apoptosis was detected by terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL).
 RESULTS: After burns, IFIT1 expression was increased at 1 h, which reached the highest level at 6 h followed by a decrease at 12 h, which reached minimum level at 24 h. The differences between groups were significant (P<0.01). The caspase-3 and -8 levels significantly increased after burns in a time-dependent manner (P<0.01). Although at 0 h and 1 h there was no significant increase in liver cell apoptosis, the increase reached significance from 6 h to 24 h (P<0.01).
 CONCLUSION: The increase in IFIT1 expression after severe burns promotes liver cell apoptosis.

[Effect of ropivacaine on proliferation and migration of rat bone marrow mesenchymal stem cells].

OBJECTIVE: To observe the influence of ropivacaine on the proliferation and migration of rat bone marrow mesenchymal stem cells (BMSCs) and provide basis for the clinical application of BMSCs. METHODS: Rat BMSCs were isolated and cultured by adherence method. Surface markers of BMSCs were examined by flow cytometry. Multipotent differentiation of BMSCs was detected by induced adipogenesis, osteogenesis and muscular differentiation. Proliferation of BMSCs was examined by CCK-8 and Brdu incorporation after ropivacaine treatment at different concentrations. Migration of BMSCs was tested by cell scratch assay and Millicell experiment. RESULTS: Cultured cells had representative appearance and surface markers of BMSC, and they had potential multiple differentiation. Ropivacaine treatment at 50 and 100 µmol/L significantly reduced the proliferation rate of BMSCs and Brdu incorporation rate. There was significant difference compared with the control group (P<0.05). Cellular scratch assay and migration experiment indicated that ropivacaine significantly reduced the migration of BMSCs. There was significant difference compared with the control group (P<0.05). All these mentioned effects of ropivacaine on BMSCs were dose-dependent. There was significant difference between groups (P<0.05). CONCLUSION: Ropivacaine can significantly reduce the proliferation and migration of rat BMSCs, suggesting that the influence of local anesthetics on BMSCs has to be taken into account when BMSCs are used in clinical practice.

Schisandrin A protects against isoproterenol­induced chronic heart failure via miR­155.

Schisandrin A (Sch A) has a protective effect on cardiomyocytes. Circulating miR­155 levels are related to chronic heart failure (CHF). The present study aimed to clarify the role and the molecular mechanism of Sch A in CHF. C57BL/6JGpt mice were used for an isoproterenol (ISO)­induced CHF model to collect heart samples. Echocardiography was employed to detect heartbeat indicators. The degree of myocardial hypertrophy was evaluated based on the measurement of heart weight (HW), body weight (BW) and tibia length (TL) and the observation using hematoxylin­eosin staining. Sprague­Dawley rats were purchased for the separation of neonatal rat ventricular myocytes (NRVMs), which were treated with ISO for 24 h. Transfection regulated the level of miR­155. The viability of NRVMs was detected via MTT assay. The mRNA and protein levels were measured via reverse transcription­quantitative PCR and western blotting and immunofluorescence was used to detect the content of α­smooth muscle actin (α­SMA). Treatment with ISO resulted in rising left ventricular posterior wall thickness, intra­ventricular septum diastole, left ventricular end diastolic diameter, left ventricular end systolic diameter, HW/BW, HW/TL and falling ejection fraction and fractional shortening, the trend of which could be reversed by Sch A. Sch A ameliorated myocardial hypertrophy in CHF mice. In addition, Sch A inhibited ISO­induced upregulated expressions of atrial natriuretic peptide, B­type natriuretic peptide, B­myosin heavy chain and miR­155 in myocardial tissue. Based on the results in vitro, Sch A had no significant effect on the viability of NRVMs when its concentration was <24 µmol/l. Sch A inhibited the levels of miR­155, α­SMA and the phosphorylation levels of AKT and cyclic AMP response­element binding protein (CREB) in ISO­induced NRVMs, which was reversed by the upregulation of miR­155. Schisandrin A mediated the AKT/CREB signaling pathway to prevent CHF by regulating the expression of miR­155, which may shed light on a possible therapeutic target for CHF.

The clinical effects of ultrasound-guided microwave ablation in the treatment of primary hepatic carcinoma: Protocol for a retrospective clinical observation.

INSTRUCTION: Despite the continuous advancement of liver cancer diagnosis technology and level, there are still nearly two-thirds of patients with primary liver cancer that are already advanced at the time of diagnosis. Ultrasound-guided microwave ablation, as a palliative treatment for intermediate and advanced liver cancer, is currently recognized internationally Standard treatment for patients with unresectable hepatocellular carcinoma. However, recently, some scholars hold that ultrasound-guided microwave ablation does not guarantee complete inactivation of tumor lesions. METHODS/DESIGN: This study will evaluate the safety and effectiveness of ultrasound-guided microwave ablation in patients with advanced hepatocellular carcinoma through retrospective analysis. This study will follow a clinical research method with consecutive enrollment. The overall survival rate, objective tumor remission rate, serum indices and incidence of adverse effects after treatment will be counted for patients. DISCUSSION: At present, there are no good treatment options for intermediate and advanced hepatocellular carcinoma. Therefore, there is a strong demand to explore the individualized multidisciplinary combined treatment model based on ultrasound-guided microwave ablation. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2100052107, Registered on 17 October 2021.

Enhanced AMPA receptor-mediated excitatory transmission in the rodent rostromedial tegmental nucleus following lesion of the nigrostriatal pathway.

The GABAergic rostromedial tegmental nucleus (RMTg) has reciprocal connections with the dopaminergic ventral tegmental area and substantia nigra pars compacta (SNc), and is involved in inhibitory control of monoaminergic nuclei. At present, it is not clear whether unilateral 6-hydroxydopamine lesions of the SNc in rats affect AMPA receptor-mediated excitatory transmission in the RMTg. Here we found that lesions of the SNc in rats increased the firing rate of GABAergic neurons and the level of glutamate in the RMTg compared to sham-operated rats. Intra-RMTg injection of AMPA receptor agonist (S)-AMPA increased the firing rate of the GABAergic neurons in both sham-operated and the lesioned rats, while AMPA receptor antagonist NBQX decreased the firing rate of the neurons. Further, intra-RMTg injection of (S)-AMPA decreased the levels of dopamine and serotonin in the medial prefrontal cortex (mPFC) in the two groups of rats; conversely, NBQX increased the levels of dopamine and serotonin. Compared to sham-operated rats, the duration of (S)-AMPA and NBQX action on the firing rate of GABAergic neurons in the RMTg and release of doapmine and serotonin in the mPFC was prolonged in the lesioned rats. In addition, lesions of the SNc in rats increased protein expression of t-GluR1 and p-GluR1-S831 subunits compared to sham-operated rats. Therefore, these changes in the lesioned rats are associated with increased release of glutamate and up-regulated expression of GluR1 subunit-containing AMPA receptors in the RMTg, which suggest that degeneration of the nigrostriatal pathway enhances AMPA receptor-mediated excitatory transmission in the RMTg.

[A case-control study on serum organochlorines residues, genetic polymorphisms of glutathione S-transferase T1 and the risks of breast cancer].

OBJECTIVE: To study the potential effect of gene-environment interaction between glutathione S-transferase T1 (GSTT1) and serum organochlorines residues on the risk of breast cancer in women, in China. METHODS: 70 newly diagnosed female breast cancer patients and 30 controls from September 2006 to October 2007 were interviewed using the same questionnaire to obtain information regarding exposure to those risks. Organochlorine residues level in serum was measured by gas chromatography (GC). Genotypes of GSTT1 polymorphisms were analyzed by multiplex allele-specific polymerase chain reaction (PCR). Interaction indexes (gamma) were calculated to determine the type of gene-environment interaction. RESULTS: After adjusting the confounding factors, results showed that interaction existed in genetic polymorphisms of GSTT1 and dichlorodiphenyltrichloroethane (DDT)/hexachlorocyclohexane (HCH) residues, with interaction indexes (gamma) value as 1.352 and 1.528. CONCLUSION: Genetic and environmental hazard factors had a co-effect on the development of breast cancer while genetic polymorphisms of GSTT1 and DDT/HCH expressed an interaction to breast cancer.