4-Methyl-2,6-diformylphenol based biocompatible chemosensors for pH: discrimination between normal cells and cancer cells

Two compounds, namely, 2-hydroxy-5-methyl-3-((pyridin-2-ylimino)methyl)benzaldehyde (HM-2py-B) and 2-hydroxy-5-methyl-3-((pyridin-3-ylimino)methyl)benzaldehyde (HM-3py-B), have been explored as fluorescent chemosensors for pH. HM-2py-B and HM-3py-B were synthesized by single step condensation reaction between 4-methyl-2,6-diformylphenol and the appropriate aminopyridine. These compounds have been characterized by elemental analysis, FT-IR, ¹H NMR, ¹³C NMR, ESI mass spectrometry, and absorption and fluorescence spectroscopy. Their structures have been confirmed by single crystal X-ray diffraction analysis. Both of the compounds show low emission at 530 nm at low pH. Fluorescence intensity increases with the increase in pH. With the alteration in pH of the medium from 4.0 to 10.0, the fluorescence intensity at 530 nm enhances by 66 and 195 fold for HM-2py-B and HM-3py-B, respectively. pK_a values of HM-2py-B and HM-3py-B have been determined to be 7.15 and 6.57, respectively. Fluorescence increase occurs mainly due to deprotonation of the phenolic OH group. Several cations and anions could not induce significant change in fluorescence behavior for both of the probes. The quantum yield and life-time enhance significantly when the pH of the medium is changed from 5.0 to 9.0. Naked eye identification of different pH environments is possible by using these compounds. Some theoretical calculations have been carried out to support experimentally obtained spectral transitions. As cancer cell has a pH in the range of 5.5–7.0 in comparison to normal cell pH of 7.4, these probes have been used effectively to discriminate between normal cells and cancer cells.

Two 4-methyl-2,6-diformylphenol based compounds with pyridylamine have been established as chemosensors for pH. The probes are able to differentiate between normal cells and cancer cells.     

Biocompatible implant mimicking cartilage: A new horizon for reconstructive facial field

Cartilage is avascular with limited to no regenerative capacity, so its loss could be a challenge for reconstructive surgery. Current treatment options for damaged cartilage are also limited. In this aspect there is a tremendous need to develop an ideal cartilage-mimicking biomaterial that could repair maxillofacial defects. Considering this fact in this study we have prepared twelve silicone-based materials (using Silicone 40, 60, and 80) reinforced with hydroxyapatite, tri-calcium phosphate, and titanium dioxide which itself has proven their efficacy in several studies and able to complement the shortcomings of using silicones. Among the mechanical properties (Young’s modulus, tensile strength, percent elongation, and hardness), hardness of Silicone-40 showed similarities with goat ear (P > .05). Silicone peaks have been detected in FTIR. Both AFM morphology and SEM images of the samples confirmed more roughed surfaces. All the materials were nonhemolytic in hemocompatibility tests, but among the twelve materials S2, S3, S5, and S6 showed the least hemolysis. For all tested bacterial strains, adherence was lower on each material than that grown on the plain industrial silicone material which was used as a positive control. S2, S3, S5, and S6 samples were selected as the best based on mechanical characterizations, surface characterizations, in vitro hemocompatibility tests and bacterial adherence activity. So, outcomes of this present study would be promising when developing ideal cartilage-mimicking biocomposites and their emerging applications to treat maxillofacial defects due to cartilage damage.     

Acute and subchronic dermal toxicity of Vitex negundo essential oil

Vitex negundo is a common herb in different herbal formulation. The potential acute and sub-chronic dermal toxicities were evaluated as per OECD (Organization for Economic Cooperation and Development) guidelines 402 and 411, respectively. Both sexes of Wistar rats were exposed to Vitex negundo oil of 2000?mg/kg body weight for acute dermal toxicity, whereas in the dermal sub-chronic toxicity study, rats were exposed to Vitex negundo oil 250, 500 and 1000?mg/kg body weight, respectively, for five times a week for 90?d. In acute and sub-chronic toxicity studies, all animals were normal without any behavioral, serum biochemistry, hematology, necroscopical and histopathological changes. The no observed effect level (NOEL) and no observed adverse effect level (NOAEL) of Vitex negundo oil were 250 and 1000?mg/kg/day, respectively. Vitex negundo oil is under the category 5 (Unclassified) according to the Globally Harmonized System, with an LD₅₀ value of over 2000?mg/kg.     

Modern approaches to the treatment of breast cancer

Breast cancer is the most common cause of cancer death in women in this country. Until recently, the traditional treatment has been radical surgery with or without radiation therapy for patients with primary breast cancer, and palliative endocrine therapy followed by chemotherapy for patients with advanced disease. These treatments have met with limited effectiveness in terms of eradicating the disease. Studies in the past decade have given cause for optimism for breast cancer patients. Adjuvant systemic therapy after local treatment appears promising for certain subsets of patients with primary breast cancer. The development of estrogen receptor assays has markedly changed our approach to the disease and improved patient care. Estrogen receptor is an important prognostic factor and is useful in planning appropriate therapy for patients with primary breast cancer as well as those with advanced disease. Further research is urgently needed to improve the dismal survival of certain women with this common malignancy.     

Synthesis,Characterization, and Biological Evaluation of 99mTc(CO)3‐Labeled Peptides for Potential Use as Tumor Targeted Radiopharmaceuticals

During the past decade, several peptides containing Arg‐Gly‐Asp sequence have been conjugated with different chelating agents for labeling with various radionuclides for the diagnosis of tumor development. In this study, we report the synthesis of two tetrapeptides (Asp‐Gly‐Arg‐His and Asp‐Gly‐Arg‐Cys) and one hexapeptide [Asp‐Gly‐Arg‐D‐Tyr‐Lys‐His] by changing the amino acid sequence of the Arg‐Gly‐Asp motif. Peptide synthesis was initiated from aspartic acid. Aspartic acid placed at C‐terminal end of the peptide chain can be conjugated with different drug molecules facilitating their transport to the site of action. The peptides were synthesized in excellent yield and labeled using freshly prepared [^99mTc(CO)₃(H₂O)₃]⁺ intermediate. A complexation yield of over 97% was achieved under mild conditions even at low ligand concentrations of 10^?2 m . Radiolabeled peptides were characterized by HPLC and were found to be substantially stable in saline, in His solution as well as in rat serum and tissue (kidney, liver) homogenates. Internalization studies using Ehrlich ascites carcinoma cell line showed rapid and significant internalization (30–35% at 30 min of incubation attaining maximum value of about 40–60% after 2–4 h incubation). A good percentage of quick internalization was also observed in α_vβ₃‐receptor‐positive B16F10 mouse melanoma cell line (14–16% after 30 min of incubation and 25–30% after 2–4 h incubation). Imaging and biodistribution studies were performed in Swiss albino mice bearing Ehrlich ascites tumor in right thigh. Radiolabeled peptides exhibited fast blood clearance and rapid elimination through the urinary systems. ^99mTc(CO)₃‐tetra‐Pep2 exhibited remarkable localization at tumor site (1.15%, 1.17%, and 1.37% ID/g at 2, 4, and 6 h p.i., respectively) which could be due to slow clearance of the radiolabeled peptide from blood in comparison with the other two radiolabeled peptides. However, ^99mTc(CO)₃‐hexa‐Pep exhibited the highest tumor to muscle and tumor to blood ratios among the three. The preliminary results with these amino acid–based peptides are encouraging enough to carry out further experiments for targeting tumor.     

Effect of ECG-derived respiration (EDR) on modeling ventricular repolarization dynamics in different physiological and psychological conditions

Ventricular repolarization dynamics is an important predictor of the outcome in cardiovascular diseases. Mathematical modeling of the heart rate variability (RR interval variability) and ventricular repolarization variability (QT interval variability) is one of the popular methods to understand the dynamics of ventricular repolarization. Although ECG derived respiration (EDR) was previously suggested as a surrogate of respiration, but the effect of respiratory movement on ventricular repolarization dynamics was not studied. In this study, the importance of considering the effect of respiration and the validity of using EDR as a surrogate of respiration for linear parametric modeling of ventricular repolarization variability is studied in two cases with different physiological and psychological conditions. In the first case study, we used 20 young and 20 old healthy subjects’ ECG and respiration data from Fantasia database at Physionet to analyze a bivariate QT–RR and a trivariate \({\text{QT}}{-}{\text{RR}}{-}{\text{RESP}}\,{\text{or}}\,{\text{QT}}{-}{\text{RR}}{-}{\text{EDR}}\) model structure to study the aging effect on cardiac repolarization variability. In the second study, we used 16 healthy subjects’ data from drivedb (stress detection for automobile drivers) database at Physionet to do the same analysis for different psychological condition (i.e., in stressed and no stress condition). The results of our study showed that model having respiratory information (QT–RR–RESP and QT–RR–EDR) gave significantly better fit value (p < 0.05) than that of found from the QT–RR model. EDR showed statistically similar (p > 0.05) performance as that of respiration as an exogenous model input in describing repolarization variability irrespective of age and different mental conditions. Another finding of our study is that both respiration and EDR-based models can significantly (p < 0.05) differentiate the ventricular repolarization dynamics between healthy subjects of different age groups and with different psychological conditions, whereas models without respiration or EDR cannot distinguish between the groups. These results established the importance of using respiration and the validity of using EDR as a surrogate of respiration in the absence of respiration signal recording in linear parametric modeling of ventricular repolarization variability in healthy subjects.     

Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2

Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.     

二十碳五烯酸对三种肝癌细胞系作用的实验研究

目的 探讨二十碳五烯酸（eicosapentaenoic acid,EPA)对3种肝癌细胞系作用。方法 EPA作用于HepG2（携带有野生型p53基因）、Huh7（携带有突变型p53基因）和Hep3B(p53基因缺失）这3种肝癌细胞系,通过细胞计数、DNA电泳、流式细胞技术和末端转移酶标记技术等来检测EPA对这3种细胞系的作用和可能的机制。结果 EPA主要是通过诱导HepG2肝癌细胞系的细胞凋亡来抑制其生长,而且这种抑制作用呈现出时间和剂量依赖的关系。而且同时发现EPA对于Huh7和Hep3B这两种肝癌细胞系无明显抑制作用。结论 细胞凋亡的诱导可能是EPA抑制HepG2肝癌细胞系生长的主要机制。而且p53基因可能参与EPA诱导HepG2细胞系细胞凋亡的过程。