Chemokine CCL2 promotes cardiac regeneration and repair in myocardial infarction mice via activation of the JNK/STAT3 axis.

Stimulation of adult cardiomyocyte proliferation is a promising strategy for treating myocardial infarction (MI). Earlier studies have shown increased CCL2 levels in plasma and cardiac tissue both in MI patients and mouse models. In present study we investigated the role of CCL2 in cardiac regeneration and the underlying mechanisms. MI was induced in adult mice by permanent ligation of the left anterior descending artery, we showed that the serum and cardiac CCL2 levels were significantly increased in MI mice. Intramyocardial injection of recombinant CCL2 (rCCL2, 1 µg) immediately after the surgery significantly promoted cardiomyocyte proliferation, improved survival rate and cardiac function, and diminished scar sizes in post-MI mice. Alongside these beneficial effects, we observed an increased angiogenesis and decreased cardiomyocyte apoptosis in post-MI mice. Conversely, treatment with a selective CCL2 synthesis inhibitor Bindarit (30 µM) suppressed both CCL2 expression and cardiomyocyte proliferation in P1 neonatal rat ventricle myocytes (NRVMs). We demonstrated in NRVMs that the CCL2 stimulated cardiomyocyte proliferation through STAT3 signaling: treatment with rCCL2 (100 ng/mL) significantly increased the phosphorylation levels of STAT3, whereas a STAT3 phosphorylation inhibitor Stattic (30 µM) suppressed rCCL2-induced cardiomyocyte proliferation. In conclusion, this study suggests that CCL2 promotes cardiac regeneration via activation of STAT3 signaling, underscoring its potential as a therapeutic agent for managing MI and associated heart failure.

Prognostic Analysis and Risk Factors Associated with Fetal Ventriculomegaly.

BACKGROUND: This study aimed to investigate the clinical outcome and related risk factors of fetal lateral ventriculomegaly (VM). METHODS: A retrospective analysis was performed on 255 cases diagnosed as fetal VM. Prenatal imaging examination was carried out. The pregnancy outcomes were investigated through follow-up. According to the prognosis of children, they were divided into case group and control group. Multivariate logistic regression was used to analyze the factors influencing the prognosis of hydrocephalus. RESULTS: After excluding the cases with either loss of follow-up or incomplete information, 102 cases were followed up. Twelve cases with poor prognosis were set as the case group. According to the maternal age, gestational age, gender of children, and follow-up time, 3 cases were selected from the other 90 cases for each child in the case group, respectively, and selected as the control group. Paired comparative analysis was performed on 48 cases. Using prognosis as a dependent variable, multivariate logistic regression analysis of the statistically significant factors indicated that the change speed of width ratio (CSWR) and maximum lateral ventricular width (MW) were associated with fetal prognosis. CONCLUSIONS: Our results suggested that CSWR and MW may have the value of predicting fetal prognosis.

Hematoporphyrin derivative-mediated photodynamic techniques for the diagnosis and treatment of chordoma.

BACKGROUND: Chordoma is a rare congenital low-grade malignant tumor characterized by infiltrative growth. It often tends to compress important intracranial nerves and blood vessels, making its surgical treatment extremely difficult. Besides, the efficacy of radiotherapy and chemotherapy is limited. The photosensitizer hematoporphyrin derivative (HPD) can emit red fluorescence under 405 nm excitation and produce reactive oxygen species for tumor therapy under 630 nm excitation. Herein, we investigated the effects of the photosensitizer hematoporphyrin derivative (HPD) on different cell lines of chordoma and xenograft tumors under 405 nm and 630 nm excitation. METHODS: The photosensitizer hematoporphyrin derivative (HPD) and Two different chordoma cell lines (U-CH1, JHC7) were used for the test. The in vitro experiments were as follows: (1) the fluorescence intensity emitted by chordoma cells excited by different 405 nm light intensities was observed under a confocal microscope; (2) the Cell Counting Kit-8 (CCK-8) assay was performed to detect the effects of different photosensitizer concentrations and 630 nm light energy densities on the activity of chordoma cells. In the in vivo experiments, (3) Fluorescence visualization of chordoma xenograft tumors injected with photosensitizer via tail vein under 405 nm excitation; (4) Impact of 630 nm excitation of photosensitizer on the growth of chordoma xenograft tumors. RESULTS: (1) The photosensitizers in chordoma cells and chordoma xenografts of nude mice were excited by 405 nm to emit red fluorescence; (2) 630 nm excitation photosensitizer reduces chordoma cell activity and inhibits chordoma xenograft tumor growth in chordoma nude mice. CONCLUSION: Photodynamic techniques mediated by the photosensitizer hematoporphyrin derivatives can be used for the diagnosis and treatment of chordoma.

Predictive Value of the Systemic Immune Inflammation Index for Adverse Outcomes in Patients With Acute Ischemic Stroke.

Background and Purpose: The systemic immune-inflammation index, a new index based on platelets, neutrophils and lymphocytes, has been shown to be associated with outcomes of patients with venous sinus thrombosis and cancer. However, its application in acute ischemic stroke has rarely been reported. Therefore, we examined the relationship between systemic immune-inflammation index levels at hospital admission and the outcomes of patients 3 months after onset, and plotted a nomogram to predict the probability of adverse outcomes in patients with acute ischemic stroke. Methods: We retrospectively analyzed a total of 208 patients with acute ischemic stroke who were admitted between January 2020 and December 2020, and recorded the modified Rankin score 3 months later. A modified Rankin score ≥ 3 was defined as an adverse outcome. Age, sex, NIHSS score, SII, hypertension and coronary heart disease were included in the binary logistic regression, and the nomogram was plotted with a regression equation. Results: Receiver operating characteristic (ROC) curve analysis indicated that the best cutoff value of the systemic immune-inflammation index was 802.8, with a sensitivity of 70.9% and specificity of 58.2% (area under the curve: 0.657, 95% confidence interval: 0.572-0.742). The nomogram had a C index of 0.802. The average error of the calibration curves of the training set and the validation set was 0.021 and 0.034, respectively. Conclusion: The systemic immune-inflammation index is associated with short-term adverse outcomes in patients with acute ischemic stroke, and the nomograms can predict the risk of adverse outcomes in patients with acute ischemic stroke.

[Influence of introducing hexyloxy group on fluorescence property of 4-nitrostilbene compounds].

Two new stilbene derivatives, 4-methacryloxyl-4'-nitrostilbene (NS) and 4-(6-methacryloxyl)-hexyloxy-4'-nitrostilbene (HNS), were synthesized and characterized by FTIR, UV-Vis, HPLC and 1H NMR. The influence of structure, concentration and solvent polarity on the fluorescence of the two compounds was investigated in the present paper. Results showed that both NS and HNS have concentration quenching effect and the fluorescence spectrum exhibited a red shift with the increase in the polarity of solvents. Moreover, the donor-acceptor structure is formed in HNS due to the introduction of donor group hexyloxy, which leads to a 72 nm red shift of the maximum wavelength of fluorescence compared with NS, and the fluorescence generated from such composite in DMF solution would change from yellow to orange.

[Study on styrene derivatives with stilbene-like pendant: synthesis and the fluorescence properties].

A series of styrene derivatives with stilbene-like pendant were synthesized through heterogeneous Wittig reaction of triphenyl-(4-vinyl)-benzylphosphornium chloride with aromatic aldehydes. The substituted styrenic monomer, 4-(2-aryl)-vinyl-styrene, was strongly photoluminescent in solution and in solid state. Introduced electron-pushing substituents and lengthened conjugation both enhanced the emission intensity and led to a red shift of emission bands, with the maximum emission wavelength shifted from 378 to 494 nm. The fluorescece quantum efficiencies were determined by employing quinine sulfate as reference; and 4-(2-anthryl)-vinyl-styrene (AVS) possessed the highest quantum efficiency (lambda = 494 nm, phi(f) = 0.635).

Inhibitory effect of D3 dopamine receptors on neuropeptide Y­induced migration in vascular smooth muscle cells.

Abnormal migration of vascular smooth muscle cells (VSMCs) serves an important role in hypertension, atherosclerosis and restenosis following angioplasty, which is regulated numerous hormonal and humoral factors, including neuropeptide Y (NPY) and dopamine. Dopamine and NPY are both sympathetic neurotransmitters, and a previous study reported that NPY increased VSMC proliferation, while dopamine receptor inhibited it. Therefore, the authors wondered whether or not there is an inhibitory effect of dopamine receptor on NPY­mediated VSMC migration. The present study demonstrated that stimulation with NPY dose­dependence (10­10­10­7M, 24 h) increased VSMC migration, the stimulatory effect of NPY was via the Y1 receptor. This is because, in the presence of the Y1 receptor antagonist, BIBP3226 (10­7 M), the stimulatory effect of NPY on VSMC migration was blocked. Activation of the D3 receptor by PD128907 dose­dependence (10­11­10­8 M) reduced the stimulatory effect of NPY on VSMC migration. The effect of PD128907 was via the D3 receptor, because the inhibitory effect of PD128907 on NPY­mediated migration was blocked by the D3 receptor antagonist, U99194. The authors' further study suggested that the inhibitory effect of the D3 receptor was via the PKA signaling pathway, in the presence of the PKA inhibitor, 14­22 (10­6 M), the inhibitory effect of PD128907 on VSMC migration was blocked. Moreover, the inhibitory effect of PD128907 was imitated by PKA activator, Sp­cAMP [S], in the presence of Sp­cAMP [S], the NPY­mediated stimulatory effect on VSMC migration was abolished. The present study indicated that activation of the D3 receptor inhibits NPY Y1­mediated migration on VSMCs, PKA is involved in the signaling pathway.

[Distribution and expression of peroxisome proliferator activated receptor gamma in human pituitary adenomas].

OBJECTIVE: To evaluate the distribution and expression of peroxisome proliferator activated receptor gamma (PPAR-gamma) in human pituitary adenomas. METHODS: Thirty eight consecutive surgically resected pituitary adenomas and 5 normal pituitary tissues were enrolled in the study. Immunohistochemistry was used to confirm the distribution of PPAR-gamma. Expression of PPAR-gamma was evaluated by Western blot. RESULTS: PPAR-gamma immunoreactivity was located in the nucleoli of pituitary adenoma cells. PPAR-gamma was expressed in all human pituitary adenomas and normal pituitary tissues. Its expression in pituitary adenomas was significantly higher than in normal pituitary tissues (P < 0.01), and its expression in ACTH-secreting adenomas was significantly higher than in any other type of pituitary adenomas (P < 0.05). CONCLUSIONS: PPAR-gamma may play an important role in the generation, growth, and invasion of human pituitary adenomas. It may become a novel therapeutic target for these tumors.

[Factors influencing the recurrence of Cushing's disease treated by transsphenoidal surgery].

OBJECTIVE: To explore factors influencing the recurrence of patients with Cushing's disease after transsphenoidal surgery. METHODS: We retrospectively analyzed the clinical data of 182 patients treated by transsphenoidal surgery with Cushing's disease in our department in PUMC Hospital from 1992 to 2002. RESULTS: The recurrence rates were significantly different when patients had different radiological findings (P = 0.001), operative methods (P = 0.001), histological findings (P = 0.04), and postoperative cortisol levels (P = 0.02); however, such difference was not found in term of tumor size (P = 0.43). CONCLUSION: Radiological findings, operative methods, histological findings, and postoperative cortisol estimates may be the factors influencing the recurrence of patients treated by transsphenoidal surgery.

Reconstruction of the sellar floor following transsphenoidal surgery using gelatin foam and fibrin glue.

OBJECTIVE: To introduce a new principle of sellar reconstruction and to evaluate the effectiveness of absorbable gelatin foam and fibrin glue for sellar reconstruction. METHODS: A total of 176 consecutive patients who underwent surgery for pituitary adenomas, cysts, chordomas, or subdiaphragmatic craniopharyngiomas in the sella turcica between January 2001 and April 2003 at Peking Union Medical College Hospital were enrolled. Different techniques of sellar closure and indications for each specific condition were retrospectively reviewed. RESULTS: Seventy-seven (43.7%) patients developed a visible cerebrospinal fluid (CSF) leakage during surgery. Intra-operative CSF leakage were repaired simply with gelatin foam and fibrin glue in 62 (35.2%) patients, and with autologous fat graft and sellar floor reconstruction in 15 (8.5%) patients. Postoperative CSF rhinorrhea occurred only in 1 case. There were no visual deterioration, allergic rhinitis, meningitis, pneumocranium, granulomas, or other complications associated with the reconstruction procedure. CONCLUSION: The procedure of using gelatin foam and fibrin glue and principle of cranial base reconstruction is safe and effective in preventing postoperative complications following transsphenoidal surgery.

Effect of preoperative use of long-acting octreotide on growth hormone secreting pituitary adenoma and transsphenoidal surgery.

OBJECTIVE: To investigate whether somatostatin analog octreotide long acting release (LAR) shrinks growth hormone (GH) secreting adenomas, and improves the results of subsequent transsphenoidal surgery. METHODS: Seventeen previously untreated active acromegalic patients with pituitary adenomas were treated with LAR (30 mg intramuscular injection every 28 days) for 3 months prior to transsphenoidal surgery. Clinical reaction, mean GH secretion, and tumor volume were measured under basal conditions and after LAR treatment. RESULTS: Presurgical treatment improved acromegaly symptoms and induced a significant reduction of GH under the 5 ng/mL limit in microadenoma (P < 0.05), while only 18.2% (2/11) in macroadenoma. Meanwhile, tumor shrinkage occurred in 58.8% (10/17) patients, with 1 case in the microadenoma group. All marked shrinkage (> 25%) occurred in the macroadenoma group. Statistical analysis showed tumor shrinkage caused by LAR was greater in macroadenoma group than that in microadenoma group (P < 0.05). During operation, adenoma was soft in 15 cases, with the exception of 2 cases in which the soft tumor was divided by fibrous septa, but all tumor removal was smooth. CONCLUSIONS: A short term administration of preoperative LAR may induce a significant decrease in GH-secretion level and adenoma volume. Presurgical use of octreotide LAR improves surgical results especially in macroadenomas.

Arsenic, copper, and zinc contamination in soil and wheat during coal mining, with assessment of health risks for the inhabitants of Huaibei, China.

Field studies were conducted to investigate arsenic (As), copper (Cu), and zinc (Zn) contamination in agricultural soils and wheat crops at two areas in Huaibei, China. Area A is in the proximity of Shuoli coal mine. In area B, three coal mines and a coal cleaning plant were distributed. The potential health risk of As, Cu, and Zn exposure to the local inhabitants through consumption of wheat grains was also estimated. The results showed that significantly higher (p<0.05) concentrations of As, Cu, and Zn were found in soils collected from area B than in those from area A. Arsenic concentrations in wheat sampled from area A were negatively correlated with the distance from the coal mine (p<0.001). Concentrations of Cu and Zn in wheat seedlings and grains collected from area B were significantly higher (p<0.05) than in those collected from area A, with the exception of Zn in wheat seedlings. Concentrations of Cu and Zn in most wheat grain samples were above the permissible limits of Cu and Zn in edible plants set by the Food and Agriculture Organization/World Health Organization. The hazard index of aggregate risk through consumption of wheat grains was 2.3-2.4 for rural inhabitants and 1.4-1.5 for urban inhabitants. The average intake of inorganic As for rural inhabitants in Huaibei was above 10 µg day(-1). These findings indicated that the inhabitants around the coal mine are experiencing a significant potential health risk due to the consumption of locally grown wheat.