The action of topical application of Vitamin B12 ointment on radiodermatitis in a porcine model.

Radiodermatitis is an inevitable side effect of radiotherapy in cancer treatment and there is currently no consensus on effective drugs for treating the condition. Vitamin B12 is known to be effective for repairing and regenerating damaged skin. However, there are few studies on the use of Vitamin B12 for treating radiodermatitis. This study explored the therapeutic efficacy and mechanism of action of Vitamin B12 ointment on radiodermatitis. A porcine model of grade IV radiodermatitis was established. The ointment was applied for 12 weeks after which histological staining, transmission electron microscopy, RT-qPCR, western blotting, and gene sequencing were performed for the evaluation of specific indicators in skin samples. After 12 weeks of observation, the Vitamin B12 treatment was found to have significantly alleviated radiodermatitis. The treatment also significantly reduced the expression levels of NF-κB, COX-2, IL-6, and TGF-ß in the skin samples. The pathways involved in the effects of the treatment were identified by analysing gene expression. In conclusion, Vitamin B12 ointment was found to be highly effective for treating radiodermatitis, with strong anti-radiation, anti-inflammatory, and anti-fibrosis effects. It is thus a promising drug candidate for the treatment of severe radiodermatitis.

Overexpression of microRNA-205-5p exerts suppressive effects on stem cell drug resistance in gallbladder cancer by down-regulating PRKCE.

Some microRNAs (miRs or miRNAs) have been reported to function as tumor suppressors in gallbladder cancer (GBC). However, the specific effect of miR-205-5p on GBC remains unclear. The objective of the present study was to unravel the effects of miR-205-5p on the drug resistance in GBC. For this purpose, the expression of miR-205-5p and protein kinase C ϵ (PRKCE) was quantified in the peripheral blood sample harvested from GBC patients and healthy volunteers. Then the relationship between miR-205-5p and PRKCE was validated. After isolating the GBC stem cells, ectopic expression and depletion experiments were conducted to analyze the effect of miR-205-5p and PRKCE on cell proliferation, drug resistance, apoptosis, and colony formation rate as well as the expression of apoptotic factors (Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), and cleaved caspase 3). Finally, the mouse xenograft model of GBC was established to verify the function of miR-205-5p in vivo. Intriguingly, our results manifested that miR-205-5p was down-regulated, while PRKCE was up-regulated in peripheral blood samples and stem cells of patients with GBC. Moreover, miR-205-5p targeted PRKCE and negatively regulated its expression. The overexpression of miR-205-5p or silencing of PRKCE inhibited the drug resistance, proliferation, and colony formation rate while promoting apoptosis of GBC stem cells. Additionally, the overexpression of miR-205-5p attenuated drug resistance to gemcitabine but promoted the gemcitabine-induced cell apoptosis by inhibiting the PRKCE in vivo. Overall, an intimate correlation between miR-205-5p and PRKCE is a key determinant of drug resistance of GBC stem cells, thus, suggesting a novel miR-205-5p-based clinical intervention target for GBC patients.

MG53 protects against contrast-induced acute kidney injury by reducing cell membrane damage and apoptosis.

Mitsugumin 53 (MG53) is a tripartite motif family protein that has been reported to attenuate injury via membrane repair in different organs. Contrast-induced acute kidney injury (CI-AKI) is a common complication caused by the administration of iodinated contrast media (CM). While the cytotoxicity induced by CM leading to tubular cell death may be initiated by cell membrane damage, we wondered whether MG53 alleviates CI-AKI. This study was designed to investigate the effect of MG53 on CI-AKI and the underlying mechanism. A rat model of CI-AKI was established, and CI-AKI induced the translocation of MG53 from serum to injury sites on the renal proximal tubular (RPT) epithelia, as illustrated by immunoblot analysis and immunohistochemical staining. Moreover, pretreatment of rats with recombinant human MG53 protein (rhMG53, 2 mg/mL) alleviated iopromide-induced injury in the kidney, which was determined by measuring serum creatinine, blood urea nitrogen and renal histological changes. In vitro studies demonstrated that exposure of RPT cells to iopromide (20, 40, and 80 mg/mL) caused cell membrane injury and cell death, which were attenuated by rhMG53 (10 and 50 µg/mL). Mechanistically, MG53 translocated to the injury site on RPT cells and bound to phosphatidylserine to protect RPT cells from iopromide-induced injury. In conclusion, MG53 protects against CI-AKI through cell membrane repair and reducing cell apoptosis; therefore, rhMG53 might be a potential effective means to treat or prevent CI-AKI.

Cytotoxic and anti-inflammatory active plicamine alkaloids from Zephyranthes grandiflora.

Phytochemical investigation on the 95% EtOH extract of the whole plants of Zephyranthes grandiflora resulted in the isolation of six new 4a-epi-plicamine-type alkaloids, zephygranditines A-F (1-6), including three novel 11,12-seco-plicamine-type alkaloids. The structures of the isolated compounds were established based on 1D and 2D (1H1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated alkaloids were tested in vitro for cytotoxic potential against seven malignant melanoma cell lines and inhibitory activity for nitric oxide (NO) production and Cox-1/Cox-2. As a result, alkaloids 1-3 exhibited some cytotoxic activity against all the tested tumor cell lines with IC50 values <20 µM and 1 and 2 displayed anti-inflammatory activity in both assay of inhibitory activity for nitric oxide production and Cox-1/Cox-2.

Novel oncogenic and chemoresistance-inducing functions of resistin in ovarian cancer cells require miRNAs-mediated induction of epithelial-to-mesenchymal transition.

Resistin plays a role in the growth, proliferation, angiogenesis, metastasis and therapeutic resistance in different cancers. However, such effects of resistin have never been evaluated in ovarian cancer, a deadly gynecological malignancy. We observed a significant induction of ovarian cancer cells' growth, invasion and cisplatin resistance, and established a mechanism of resistin action that included induction of EMT and stemness, as evidenced by down-regulated epithelial marker e-cadherin and up-regulated mesenchymal markers vimentin/ ZEB1 and stemness markers sox2, oct4 and nanog. The mechanism also included suppression of tumor suppressor miRNAs, let-7a, miR-200c and miR-186. Over-expression of these miRNAs significantly reversed the resistin-mediated effects on invasion and chemoresistance. We further validated our results in vivo where resistin administration significantly enhanced tumor growth in mice. Our results provide first evidence for such oncogenic effects of resistin in ovarian cancer models and a rationale for future studies to further understand the mechanistic role of resistin in ovarian cancer invasiveness, metastasis and therapy resistance.

Computed Tomography-Guided Interstitial Brachytherapy for Locally Advanced Cervical Cancer: Introduction of the Technique and a Comparison of Dosimetry With Conventional Intracavitary Brachytherapy.

OBJECTIVE: We present a new technique of 3-dimensional computed tomography-guided interstitial (IS) brachytherapy (BT) for locally advanced cervical cancer, offering a more advantageous clinical treatment approach. MATERIALS/METHODS: Interstitial BT was performed using an applicator combining uterine tandem and metal needles; needles were inserted freehand under real-time 3-dimensional computed tomography guidance. Twenty-eight patients with bulky tumors and/or parametrial extension (tumor size > 5 cm) after external beam radiotherapy received IS BT. Dosimetric outcomes of the IS BT including the total dose (external beam radiotherapy and high dose-rate BT) D90 for the high-risk clinical target volume (HR-CTV) and D2cc for the organs at risk (OARs) were investigated and compared with a former patient group consisting of 30 individuals who received the conventional intracavitary (IC) BT. RESULTS: The mean D90 values for HR-CTV in the IC BT and IS BT groups were 76.9 ± 5.7 and 88.1 ± 3.3 Gy, respectively. Moreover, 85.7% of the patients received D90 for HR-CTV of 87 Gy or greater in the IS BT group, and only 6.7% of the patients received D90 for HR-CTV of 87 Gy or greater in the IC BT group. The D2cc for the bladder, rectum, and sigmoid were 84.7 ± 6.8, 69.2 ± 4.2, and 67.8 ± 4.5 Gy in the IC BT group and 81.8 ± 6.5, 66.8 ± 4.0, and 64.8 ± 4.1 Gy in the IS BT group. The mean number of needles was 6.9 ± 1.4, with a mean depth of 2.9 ± 0.9 mm for each IS BT. Interstitial BT was associated with only minor complications. CONCLUSIONS: The IS BT technique resulted in better dose-volume histogram parameters for large volume tumors (>5 cm) compared with the conventional IC BT and acceptable risk of acute complications in locally advanced cervical cancer and is clinically feasible.

Clinical feasibility of interstitial brachytherapy using a "hybrid" applicator combining uterine tandem and interstitial metal needles based on CT for locally advanced cervical cancer.

PURPOSE: To explore the dosimetric advantage of target volume and surrounding normal tissue by using interstitial (IS) brachytherapy (BT) based on three-dimensional CT in locally advanced cervical cancer, as a simple and effective clinical treatment approach. METHODS AND MATERIALS: Fifty-two patients with poor tumor response to external beam radiotherapy and a residual tumor >5 cm at the time of the first BT were included. IS BT was performed using a "hybrid" applicator combining uterine tandem and free metal needles based on three-dimensional CT. The high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume, and organs at risk were contoured. The total dose, including external beam radiotherapy (45 Gy in 25 fractions) and high-dose-rate BT (30 Gy in 5 fractions), was biologically normalized to conventional 2-Gy fractions. D90 and D100 for HR-CTV and intermediate-risk clinical target volume and D2cc for the bladder, rectum, and sigmoid were analyzed. RESULTS: The mean D90 value for HR-CTV was 88.4 ± 3.5 Gy. Totally, 88.5% of the patients received D90 for HR-CTV ≥87 Gy. The D2cc for the bladder, rectum, and sigmoid were 81.1 ± 5.6, 65.7 ± 5.1, and 63.1 ± 5.4 Gy, respectively. The mean number of needles was 6.9 ± 1.3 for each application. IS BT was associated with minor complications. CONCLUSION: IS BT using the "hybrid" applicator provides a dosimetric advantage for target volume and organs at risk in large-volume (>5 cm) tumors and is, thereby, clinically feasible. However, the long-term curative effect and possible toxicity need further clinical observation.

Association between insulin dosage and insulin usage time, and coronary artery lesions in patients with type 2 diabetes and coronary heart disease.

Insulin is used in the treatment of type 2 diabetes, with its usage reaching 30-50% in Western countries. The aim of the present study was to determine the association between insulin dosage (ID)/insulin usage time (IT) and coronary artery lesions in patients of type 2 diabetes with coronary heart disease. Based on the insulin using dosage, 353 type 2 diabetes patients were divided into the high-dose (≥0.5 IU/kg) and low-dose (<0.5 IU/kg) group. Selected coronary angiography was performed and the Gensini score was used to determine the degree of the coronary artery lesions. The homeostasis model assessment-insulin sensitivity (HOMA-IS) index was assessed by HOMA2. Data including age, gender, smoking, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG), glucose (Glu), hemoglobin A1c (HbA1c), C-peptide, ID, IT, diabetes duration time (DT), and IT/DT were collected. The association between insulin usage (both dose and time) and the coronary artery lesions in these patients was then determined. Statistical differences for the two groups for factors including C-peptide, HbA1c, ID, IT, DT, IT/DT and the Gensini score values (P<0.05) were identified. By contrast, no significant differences for factors such as gender, smoking history, age, BMI, TC, TG, LDL, HDL, fasting insulin, Glu, SBP and DBP were observed. The coronary artery damage Gensini score in insulin-insensitive individuals was significantly greater than that in the insulin-sensitive individuals. The Spearman analysis revealed that ID and IT, DT and IT/DT were positively correlated with the coronary artery damage Gensini score. The multivariate regression, the interquartile range method and receiver operating characteristic analyses showed that ID, ID/DT, IT had a greater effect on coronary vascular damage compared with DT. In conclusion, the degree of coronary artery lesions were correlated with ID, IT, DT, IT/DT. High doses of insulin or a high IT/DT ratio may aggravate coronary artery damage.

The association study on renalase polymorphism and hypertension: a meta-analysis.

Hypertension is considered a multi-factorial disease since its development is affected by both genetic and environmental factors. Intensive efforts have been focused on identifying gene(s) related to hypertension. Renalase is a recently discovered protein that expressed in kidney, heart, liver, and brain that metabolizes catecholamines, regulation of blood pressure in humans and animals. A common missense polymorphism in the flavin-adenine dinucleotide-binding domain of human renalase (Glu37Asp) has recently been described. But the reported results are not always consistent. In this meta-analysis, we examined the association between (Glu37Asp) polymorphism (rs2296545) in renalase gene and risk of hypertension. Through a systematic literature search for publications between 2007 and 2014, we summarized the data from 4 studies on polymorphism (rs2296545) in renalase gene and risk of hypertension. We did not find any association of rs2296545 with risk of hypertension in dominant model (OR=0.64; 95% CI: 0.41-1.00), recessive model (OR=1.29, 95% CI: 0.95-1.75), co-dominant model (OR=1.38, 95% CI: 0.92-2.08), and allelic model (OR=1.19; 95% CI: 0.96-1.47). The results of the present study indicated that the renalase genetic polymorphism was not associated with risk of hypertension.

Crystal structure of N-(2-hy-droxy-eth-yl)-5-nitro-isophthalamic acid monohydrate.

In the title compound, C10H10N2O6·H2O, the carb-oxy-lic acid group and the nitro group are essentially coplanar with the benzene ring [maximum deviation = 0.0264 (9) Å], while the amide group is oriented at a dihedral angle of 9.22 (5)° with respect to the benzene ring. In the crystal, classical O-H⋯O and N-H⋯O hydrogen bonds and weak C-H⋯O inter-actions link the organic mol-ecules and water mol-ecules of crystallization into a three-dimensional supra-molecular architecture.

Knockdown of Wip1 Enhances Sensitivity to Radiation in HeLa Cells Through Activation of p38 MAPK.

The objectives of the study were to investigate the functional role and potential mechanism of wild-type p53-induced phosphatase (Wip1) in cervical cancer cell line HeLa cells, along with the effect of knockdown of Wip1 in combination with γ-irradiation on the HeLa cells. Expression of Wip1 was silenced or overexpressed. After transfection, cell viability was determined. Moreover, γ-irradiation and SB203580 were performed to explore the effect of colony formation and cell apoptosis. Likewise, protein expression levels of p38, p-p38, p53, and p-p53 were assessed in the presence or not of SB203580 and overexpression of Wip1. Both the mRNA and protein levels of Wip1 were significantly decreased by transfection with Wip1-specific small interfering RNA (siRNA) but were significantly increased by transfection with pcDNA3.1-Wip1. Knockdown of Wip1 significantly decreased cell growth and colony formation ability and increased apoptotic rate. Additionally, better results were obtained by knockdown of Wip1 in combination with γ-irradiation. The protein expression levels of p-p38 (p < 0.05), p53 (p < 0.01), and p-p53 (p < 0.05) were all significantly increased by knockdown of Wip1. However, application of SB203580 reversed the effects. Our study confirms the important roles of Wip1 in cervical cancer. Knockdown of Wip1 enhances sensitivity to radiation in HeLa cells by inhibiting cell proliferation and inducing apoptosis through activation of p38 MAPK.

[Check ligament suspension for correction of congenital severe blepharoptosis].

OBJECTIVE: To evaluate the clinical result of check ligament suspension for correction of congenital severe blepharoptosis. METHODS: Since Jan. 2010 to Nov. 2010, 15 eyes in 15 cases with congenital severe blepharoptosis were treated with the check ligament suspension. Palpebral aponeurosis was exposure by opening fascia palpebral during blepharoplasty. Palpebral aponeurosis was cut off about 5 mm above the tarsus. The check ligament was seen in the intermuscular space between the segment of levator and the anterior one third of superior rectus attached to the conjunctival fornix. Congenital blepharoptosis could be corrected by suturing the check ligament and levator palpebrae superior to the upper margin of tarsal plate with 3-0 silk thread. Double eyelid plasty was carried out in the end. RESULTS: The follow-up period was 3-11 months with good cosmetic result. All the cases could close their eyes in 15 to 30 days with no complication. CONCLUSIONS: In conclusion, this technique is quite successful in raising the level of the upper eyelid in severe congenital blepharoptosis. The check ligament moves in a similar direction as the natural movement of levator muscle, so both the postoperative static and dynamic appearance of the upper lid is more natural.

[Effects of lipid-modulation and antiplatelet treatment on the endothelial lipase expression].

OBJECTIVE: To investigate the effects of lipid-modulation and antiplatelet treatment on the expression of endothelial lipase (EL) of patients with coronary artery disease (CAD), and investigate the role of EL in the development of CAD. METHODS: One hundred and fifty-seven cases were divided into three groups according to clinical manifestations and the results of coronary artery angiography: control group (n=41) with more than one risk factors of CAD and the vessel lesions was <30%; stable angina pectoris (SAP) group (n=55); acute coronary syndrome (ACS) group (n=61). The EL positive cell rate was measured 2 weeks after cessation of lipid-modulation and aspirin treatment, and 6 months after treatment with simvastatin and/or aspirin. The drug was ceased for the complications or not tolerance for the treatment. RESULTS: Except the patients in control group with aspirin treatment, the EL positive cell rate was significantly decreased among other groups [control group with simvastatin: (3.93±0.87)% vs. (5.28±1.05)%, SAP group: (8.16±2.11)% vs. (15.12±2.53)%, ACS group: (13.93±3.22)% vs. (38.44±4.36)%; SAP group with aspirin: (10.57±4.07)% vs. (14.66±2.29)%, ACS group: (18.28±5.14)% vs. (40.27±3.96)%; control group with aspirin and simvastatin: (3.13±0.87)% vs. (5.33±1.25)%, SAP group: (5.68±2.20)% vs. (14.89±2.15)%, ACS group: (7.81±3.96)% vs. (39.27±5.17)%, P<0.05 or P<0.01]. CONCLUSION: The treatment with lipid-modulation and/or antiplatelet drug may significantly decrease the expression of EL, implying that EL participates in the progression of CAD.

Ethyl 2-(2-methyl-4-nitro-1H-imidazol-1-yl)acetate.

In the title compound, C(8)H(11)N(3)O(4), the dihedral angle between the imidazole ring and the ethyl acetate plane is 103.1 (8)°. The crystal packing is stabilized by weak inter-molecular C-H⋯O and C-H⋯N hydrogen bonds.

Glycine ethyl ester hydro-chloride.

In the crystal structure of the title compound, C(4)H(10)NO(2) (+)·Cl(-) (systematic name: 3-eth-oxy-3-oxopropan-1-aminium chlor-ide), there are strong inter-molecular N-H⋯Cl, C-H⋯Cl and C-H⋯O hydrogen-bonding inter-actions between the free chloride anion and the organic cation, resulting in a two-dimensional supra-molecular network in the ab plane.

3,5-Dinitro-benzoyl chloride.

The carbonyl chloride group in the title compound, C(7)H(3)ClN(2)O(5), is disordered over two orientations with occupancies of 0.505 (5) and 0.495 (5). The mol-ecule is approximately planar, the dihedral angle between the carbonyl chloride plane and benzene ring being 9.6 (4)° in the major disorder component and 7.1 (4)° in the minor component. The nitro group at the 5-position is twisted, forming a dihedral angle of 6.7 (4)°. The crystal packing is stabilized by C-H⋯O hydrogen bonds.

4-(4-Ethoxy-benz-yl)-1,3-oxazolidin-2-one.

In the title compound, C(12)H(15)NO(3), the ethoxy-benzyl ring plane forms a dihedral angle of 60.3 (4)° with the mean plane of the oxazolidine ring. The mol-ecules are linked through N-H⋯O hydrogen bonds into a chain running in the b direction.

Methyl 9H-carbazole-9-acetate.

The title compound, C(15)H(13)NO(2), was synthesized by N-alkyl-ation of methyl bromo-acetate with 9H-carbazole. The carbazole ring system is essentially planar (mean atomic deviation = 0.0346 Å) and makes a dihedral angle of 86.5 (7)° with the methyl acetate group. Weak inter-molecular C-H⋯O hydrogen bonding is present in the crystal structure.

[Preparation of clenbuterol monoclonal antibody with subtractive immunization method].

AIM: To obtain Clenbuterol monoclonal antibodies. METHODS: Clenbuterol complete antigen was prepared with diazotization method. BALB/c mice was immunized with subtractive immunization, Clenbuterol monoclonal antibody was prepared with rule hybridoma technique. RESULTS: The mice obtained tolerance to BSA by subtractive immunization. The rate of the hybridoma cell with positive reaction which had obtained was 8.2%, and the specific clenbuterol monoclonal antibody was obtained at last. CONCLUSION: Monoclonal antibodies to micromolecule contaminant be prepared by subtractive immunization, could decrease the workload in the bolting of monoclonal antibodies, and increase the chance to obtain the antibody of expected.

[Changes of fasting serum insulin in normotensive patients with left ventricular hypertrophy].

OBJECTIVE: To explore the relationship between left ventricular hypertrophy (LVH) and serum insulin changes in normotensive patients. METHODS: Forty-two normotensive patients with LVH, who were free of hypertension, coronary artery disease and diabetes, were examined for fasting serum insulin, glucose and serum lipids, and the left ventricular mass (LVM) and left ventricular mass index (LVMI) were also measured with echocardiography, with 46 normal subjects serving as the control group. RESULTS: The levels of fasting triglyceride and insulin, as well as insulin resistance index (IRI), were higher in the LVH group than in the control group. Multifactor regression analysis showed that IRI was positively correlated to LVM and LVMI in LVH group (r=0.38, P<0.01; r=0.29, P<0.01). CONCLUSION: Hyperinsulinemia is closely correlated with LVH in these normotensive patients, and can be involved in the pathogenesis and progression of LVH.