Caerulomycin A Enhances Transforming Growth Factor-β (TGF-β)-Smad3 Protein Signaling by Suppressing Interferon-γ (IFN-γ)-Signal Transducer and Activator of Transcription 1 (STAT1) Protein Signaling to Expand Regulatory T Cells (Tregs)

Cytokines play a very important role in the regulation of immune homeostasis. Regulatory T cells (Tregs) responsible for the generation of peripheral tolerance are under the tight regulation of the cytokine milieu. In this study, we report a novel role of a bipyridyl compound, Caerulomycin A (CaeA), in inducing the generation of Tregs. It was observed that CaeA substantially up-regulated the pool of Tregs, as evidenced by an increased frequency of CD4⁺ Foxp3⁺ cells. In addition, CaeA significantly suppressed the number of Th1 and Th17 cells, as supported by a decreased percentage of CD4⁺/IFN-γ⁺ and CD4⁺/IL-17⁺ cells, respectively. Furthermore, we established the mechanism and observed that CaeA interfered with IFN-γ-induced STAT1 signaling by augmenting SOCS1 expression. An increase in the TGF-β-mediated Smad3 activity was also noted. Furthermore, CaeA rescued Tregs from IFN-γ-induced inhibition. These results were corroborated by blocking Smad3 activity, which abolished the CaeA-facilitated generation of Tregs. In essence, our results indicate a novel role of CaeA in inducing the generation of Tregs. This finding suggests that CaeA has enough potential to be considered as a potent future drug for the treatment of autoimmunity.     

Diversity analysis in Indian genotypes of linseed (Linum usitatissimum L.) using AFLP markers

AFLP fingerprinting of 45 Indian genotypes of linseed was carried out to determine the genetic relationship among them. Sixteen primer combinations produced 1142 fragments with 1129 as polymorphic and 13 as monomorphic fragments. Polymorphic fragments varied from 44 (E-ACA/M-CTA) to 94 (E-AGC/M-CAC) with an average of 70.6 fragments per primer combination. The frequency of polymorphism varied from 93.7% to 100% with an average of 98.8% across all the genotypes. The PIC value ranged from 0.19 to 0.31 with an average of 0.23 per primer combination. The primer pair E-AGC/M-CAC showed the maximum PIC value (0.31) followed by E-AGC/M-CAG (0.29), E-AAC/M-CAG (0.26) and E-AGC/M-CTA (0.25). Resolving power (RP) and marker index (MI) varied from 13.73 to 43.50 and 8.81 to 28.91 respectively. The Jaccard's similarity coefficient varied from 0.16 to 0.57 with an average of 0.26 ± 0.05. The maximum genetic similarities (57%) were detected between genotypes Him Alsi-1 and Him Alsi-2, followed by Him Alsi-1 and GS41 and GS41 and LC-54. The genotypes R-552, Himani, RKY-14, Meera, Indira Alsi-32 and Suyog were found to be more divergent genotypes. The NJ clustering grouped all the 45 genotypes into three major clusters. In general the genotypes of cluster III had high oil content and those of cluster I had low oil content. At the population level, within population variance was much higher than between populations variance.     

Synthesis and antiamoebic activity of new cyclooctadiene ruthenium(II) complexes with 2-acetylpyridine and benzimidazole derivatives

Reaction of [Ru(eta4-C8H12) (CH3CN)2 Cl2] with 2-(2-pyridyl) benzimidazole or Schiff bases derived from 2-acetylpyridine and S-methyldithiocarbazate, S-benzyldithiocarbazate and thiosemicarbazide leads to form new complexes of the type [Ru(eta4-C8H12)(L)Cl2] (where L=ligand). In vitro, most of the compounds exhibited potent activity and the Ru derivatives 1a [Ru(eta4-C8H12)(2-Acpy-SMDT)Cl2], 2a [Ru(eta4-C8H12)(2-Acpy-SBDT)Cl2] and 3a [Ru(eta4-CsH12)(2-Acpy-TSC)Cl2] were found more active than metronidazole against (HK-9) strain of Entamoeba histolytica.     

Neuronal classes in the corticoid complex of the telencephalon of the strawberry finch, <Emphasis Type="Italic">Estrilda amandava</Emphasis>

The present study, based on neurohistological techniques (Nissl-staining, Golgi-impregnation), focuses on the cytoarchitecture of the corticoid complex in the strawberry finch, Estrilda amandava. This complex in birds occupies the dorsolateral surface of the telencephalic pallium and remains subdivided into an intermediate corticoid area (CI) and a dorsolateral corticoid area (CDL). The CDL in the strawberry finch is a thin superficial part of the caudal pallium adjoining the medially situated hippocampal formation, whereas the CI is demarcated between the CDL and the parahippocampal area of telencephalon. Neurons of the corticoid complex are classified into three main cell groups: predominant projection neurons, local circuit neurons and stellate neurons. The spinous projection neurons send out distant projecting axons that typically extend several varicose collaterals. Most of these collaterals lie parallel to the ventricle. These neurons are subclassified into pyramidal neurons (localized only in the CI) and multipolar neurons (present in both the CI and CDL). The CDL also possesses small and medium-sized horizontal cells, which are bitufted or multipolar with smooth, moderately branching dendrites. The aspinous local circuit neurons extend short axons that ramify locally. Stellate neurons have sparse spinous dendrites and locally arborizing axons. The corticoid complex of birds corresponds to the lateral cerebral cortex of lizards and to the entorhinal cortex of mammals on the basis of neuronal morphology and bidirectional connections between adjacent areas. This work is supported by a D. Phil. Fellowship under the UGC scheme awarded to P. Chand and by a CSIR Fellowship (F. no. 9/1 (270)/2004 — EMR-І) awarded to R.C. Maurya.     

Cytotherapy with naive rat umbilical cord matrix stem cells significantly attenuates growth of murine pancreatic cancer cells and increases survival in syngeneic mice

Background aimsPancreatic cancer, sometimes called a ‘silent killer’, is one of the most aggressive human malignancies, with a very poor prognosis. It is the fourth leading cause of cancer-related morbidity and mortality in the USA.MethodsA mouse peritoneal model was used to test the ability of unengineered rat umbilical cord matrix-derived stem cells (UCMSC) to control growth of pancreatic cancer. In vivo results were supported by various in vitro assays, such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), direct cell count, [³H]thymidine uptake and soft agar colony assays.ResultsCo-culture of rat UCMSC with PAN02 murine pancreatic carcinoma cells (UCMSC:PAN02, 1:6 and 1:3) caused G0/G1 arrest and significantly attenuated the proliferation of PAN02 tumor cells, as monitored by MTT assay, direct cell counts and [³H]thymidine uptake assay. Rat UCMSC also significantly reduced PAN02 colony size and number, as measured by soft agar colony assay. The in vivo mouse studies showed that rat UCMSC treatment significantly decreased the peritoneal PAN02 tumor burden 3 weeks after tumor transplantation and increased mouse survival time. Histologic study revealed that intraperitoneally administered rat UCMSC survived for at least 3 weeks, and the majority were found near or inside the tumor.ConclusionsThese results indicate that naive rat UCMSC alone remarkably attenuate the growth of pancreatic carcinoma cells in vitro and in a mouse peritoneal model. This implies that UCMSC could be a potential tool for targeted cytotherapy for pancreatic cancer.     

Effect of walking stress on growth,physiological adaptability and endocrine responses in Malpura ewes in a semi-arid tropical environment

Sheep in hot semi-arid environments are mostly reared using extensive systems. In addition to thermal stress and feed scarcity, the animals need to walk long distances for grazing in this ecological zone. A study was conducted to assess the effect of long-distance walking on adaptive capability in terms of physiological, biochemical and endocrine responses in Malpura ewes. Fourteen adult Malpura non-pregnant ewes weighing between 33 and 35 kg were used in the study. The ewes were randomly allocated into two groups of seven animals each: GI (n = 7; Control), and GII (n = 7; walking stress). The animals were stall-fed with a diet consisting of 70% roughage and 30% concentrate. Both GI and GII ewes had uniform access to feed and water. The walking stress group (GII) ewes were made to walk 14 km in two spans between 0900 and 1500 hours with 1 h 30 min for each span (7 km) of walking. The ewes subjected to walking stress (GII) were prevented from grazing by applying a face mask made of cotton thread. The study was conducted for a period of two estrous cycles (35 days) during the autumn season (October–November). Physiological responses were recorded twice daily at 0800 and 1400 hours at weekly intervals. Blood samples were collected from the jugular vein at weekly intervals to study the effects of walking stress on blood biochemical and endocrine parameters. The results indicate that walking stress had significant (P < 0.05) influence on body weight, average daily gain, respiration rate (RR), rectal temperature (RT), haemoglobin (Hb), packed cell volume (PCV), plasma glucose, calcium, phosphorus, aspartate amino transferase (AST), alanine amino transferase (ALT), tri-iodo-thyronine (T₃), thyroxin (T₄), and cortisol. However, walking stress did not influence the reproductive hormone levels. The significant changes in RR, RT, plasma cortisol, T₃ and T₄ show that Malpura ewes have the capability to adapt to long-distance walking, and that adrenal and thyroid gland hormones play a significant role in such adaptation.     

Proteome profile of whole cerebellum of the mature rat

Cerebellum is an important brain region involved in motor, cognition, learning and memory functions. Proteome mapping of the 21 days old rat cerebellum identified total 285 proteins, out of which 76 proteins were not reported earlier from rat brain. This includes 49 neuronal activity-specific proteins, 7 of which are reported for the first time from the cerebellum in this study. The protein sequence data for 31 proteins reported here have been integrated in the UniProt Knowledgebase.     

Age-associated changes in erythrocyte glutathione peroxidase activity: correlation with total antioxidant potential

Oxidative stress is believed to play a central role in aging and age-associated diseases. It leads to oxidative changes in human red blood cells (RBCs) in vivo and in vitro. In this study, we evaluated the oxidative damage to the erythrocytes during aging in the humans using RBC as a model, by measuring the cytosolic antioxidant enzyme glutathione peroxidase (GPx) activity. GPx activity was found to be significantly decreased as a function of human age and positively correlated with total antioxidant capacity, while negatively correlated with SOD activity. Thus, results of the present study showed involvement of oxidative stress as one of the risk factors, which can initiate and/or promote human aging.     

Larvicidal efficacy of Aloe barbadensis and Cannabis sativa against the malaria vector Anopheles stephensi (Diptera: Culicidae)

Anopheles stephensi is the primary vector of malaria, an endemic disease in India. An effort to control An. stephensi larvae by leaf extracts of Aloe barbadensis (Liliaceae) and Cannabis sativa (Moraceae) was made under laboratory conditions. A carbon tetrachloride extract of A. barbadensis was the most effective of all the extracts tested for larvicidal activity against the anopheline larvae, with LC₅₀ 15.58 and 8.04 p.p.m. after 24 and 48 h of exposure, respectively. Thus, the leaf extract of A. barbadensis has active components that could be useful as a larvicide of ecocongenial nature against malaria vectors.