Design,synthesis, and biological evaluation of a cephalosporin-monohydroguaiaretic acid prodrug activated by a monoclonal antibody-beta-lactamase conjugate

A novel cephalosporin derivative of monohydroguaiaretic acid (cephem-M(3)N, 7) was synthesized and found to possess anticancer activity against human leukemia (K562), breast carcinoma (MCF7), human lung cancer (A549), human colon cancer (Colo205) and pancreatic cancer cells (Capan2 and MiaPaCa2). A tumor targeting fusion protein (dsFv3-beta-lactamase) was also used in conjunction with cephem-based M(3)N 7 and its potency toward K562, MCF7, A549, Colo205, Capan2, and MiaPaCa2 was found to approach that of the free M(3)N (4). In the presence of dsFv3-beta-lactamase, tumor cells were found to be much more susceptible to conjugate 7 than normal human embryonic lung (HEL) cells and normal fibroblasts (Hef522). These notions provide a new approach to the use of nordihydroguaiaretic acid (NDGA) and its derivatives for antitumor therapy.     

Discovering Candidate Chromosomal Regions Linked to Kernel Size-Related Traits via QTL Mapping and Bulked Sample Analysis in Maize

Kernel size-related traits, including kernel length, kernel width, and kernel thickness, are critical components in determining yield and kernel quality in maize (Zea mays L.). Dissecting the phenotypic characteristics of these traits, and discovering the candidate chromosomal regions for these traits, are of potential importance for maize yield and quality improvement. In this study, a total of 139 F2:3 family lines derived from EHel and B73, a distinct line with extremely low ear height (EHel), was used for phenotyping and QTL mapping of three kernel size-related traits, including 10-kernel length (KL), 10-kernel width (KWid), and 10-kernel thickness (KT). The results showed that only one QTL for KWid, i.e., qKWid9 on Chr9, with a phenotypic variation explained (PVE) of 13.4% was detected between SNPs of AX-86298371 and AX-86298372, while no QTLs were detected for KL and KT across all 10 chromosomes. Four bulked groups of family lines, i.e., Groups I to IV, were constructed with F2:3 family lines according to the phenotypic comparisons of KWid between EHel and B73. Among these four groups, Group I possessed a significantly lower KWid than EHel (P = 0.0455), Group II was similar to EHel (P = 0.34), while both Group III and Group IV were statistically higher than EHel (P < 0.05). Besides, except Group IV exhibited a similar KWid to B73 (P = 0.11), KWid of Groups I to III were statistically lower than B73 (P < 0.00). By comparing the bulked genotypes of the four groups to EHel and B73, a stable chromosomal region on Chr9 between SNPs of AX-86298372 to AX-86263154, entirely covered by qKWid9, was identified to link KWid with the positive allele of increasing phenotypic effect to KWid from B73, similar to that of qKWid9. A large amount of enzyme activity and macromolecule binding-related genes were annotated within this chromosomal region, suggesting qKWid9 as a potential QTL for KWid in maize.     

Protective effect of Didymocarpus pedicellata on ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and hyperproliferative response

Didymocarpus pedicellata R. Br. (Gesneriaceae) is widely used in traditional Indian medicines against renal afflictions. In the present study, we have revealed ethanolic extract of aerial parts of D. pedicellata to possess significant antioxidant activity and protect against ferric nitrilotriacetate (Fe-NTA) mediated renal oxidative stress, nephrotoxicity and tumor promotion response. D. pedicellata extract was found to possess a high content of total polyphenolics, exhibit potent reducing power and significantly scavenge free radicals including several reactive oxygen species (ROS) and reactive nitrogen species (RNS). The extract also significantly and dose-dependently protected against Fe-NTA plus H(2)O(2)-mediated damage to lipids and DNA. Protective efficacy of the extract was also tested in vivo against Fe-NTA mediated nephrotoxicity and tumor promotion response. Administration of Fe-NTA (9 mg/kg body weight, i.p.) to Swiss albino mice depleted renal glutathione content and activities of antioxidant and phase II metabolizing enzymes with concomitant induction of oxidative damage. Fe-NTA also incited hyperproliferation response elevating ornithine decarboxylase activity and [(3)H]-thymidine incorporation into DNA. Elevation in serum creatinine (SCr) and blood urea nitrogen (BUN), and histopathological changes were also evident and suggested Fe-NTA to afflict damage to kidney. Pretreatment of mice with D. pedicellata extract (100-200 mg/kg body weight) for 7 days not only restored antioxidant armory near normal values but also significantly protected against renal oxidative stress and damage restoring normal renal architecture and levels of renal damage markers, viz., BUN and SCr. The results of the present study indicate D. pedicellata to possess potent antioxidant and free radical scavenging activities and preclude oxidative damage and hyperproliferation in renal tissues.     

Syntheses and anti-depressant activity of 5-amino-1, 3, 4-thiadiazole-2-thiol imines and thiobenzyl derivatives

A number of new imine derivatives of 5-amino-1, 3, 4-thiadiazole-2-thiol have been synthesized, and their anti-depressant activity was tested using imipramine as reference drug. Two compounds namely 5-{[1-(4-chlorophenyl)-3-(4-methoxy-phenyl)prop-2-en-1-ylidene]-amino}-5-benzylthio-1, 3,4 -thiadiazole 4i(b) and 5-{[1-(4-chlorophenyl)-3-(4-dimethyl-aminophenyl)-prop-2-en-1-ylidene]amino}-5-benzylthio-1,3,4-thiadiazole 4i(c) have shown significant anti-depressant activity, which decreased immobility time by 77.99% and 76.26% compared to the standard imipramine (82%). All the compounds in the series have passed neurotoxicity tests.     

Serum Trace Element Levels in Febrile Convulsion

Febrile convulsion is the most common disorder in childhood with good prognosis. There are different hypotheses about neurotransmitters and trace element changes in biological fluids which can have a role in pathogenesis of febrile convulsion. In this study, serum selenium, zinc, and copper were measured by atomic absorption spectrometry in the children with febrile convulsion (n?=?30) and in the control group (n?=?30). The age and sex of the subjects were registered. Selenium and zinc were found to be significantly lower in febrile convulsion cases than in the control group (p?<?0.0001 and p?<?0.0001, respectively). There was no significant difference in the value of copper between the two groups (p?=?0.16). While selenium and zinc levels were 44.92?±?10.93 μg/l and 66.13?±?18.97 μg/dl in febrile convulsion, they were found to be 62.98?±?9.80 μg/l and 107.87?±?28.79 μg/dl in healthy children. Meanwhile, copper levels were 146.40?±?23.51 μg/dl in the patients and 137.63?±?24.19 μg/dl in the control group, respectively. This study shows that selenium and zinc play an important role in the pathogenesis of febrile convulsion.     

Development of spermatic granuloma in albino rats following administration of water extract of Heliotropium bacciferum Forssk

A spermatic granuloma is a chronic inflammatory reaction produced in response to extravasated sperm within the intertubular connective tissue. The present study investigates the possible toxic effects of water extract of Heliotropium bacciferum on the reproductive system of male albino rats and the associated potential for the development of spermatic granulomas. H. bacciferum is a herbal plant used in traditional medicine and reported to have cytotoxic effects due to pyrrolizidine alkaloids. Histological examinations revealed no changes in the tissues of the testes, although, some changes were detected in the cauda epididymis, the most important of which was the development of small lesions of spermatic granulomas. Clear gaps were observed between the epithelial linings of the epididymal tubules.