Curcumin ameliorated myocardial infarction by inhibition of cardiotoxicity in the rat model

Cardiovascular diseases are the main cause of death globally. Many attempts have been done to ameliorate the pathological changes after the occurrence of myocardial infarction. Curcumin is touted as a polyphenol phytocompound with appropriate cardioprotective properties. In this study, the therapeutic effect of curcumin was investigated on acute myocardial infarction in the model of rats. Rats were classified into four groups; control, isoproterenol hydrochloride (ISO) (100 mg/kbw), curcumin (50 mg/kbw), and curcumin plus ISO treatment groups. After 9-day administration of curcumin, levels of lactate dehydrogenase (LDH), creatine kinase (CK), and cardiac troponin I (cTnI) were determined. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents were measured to investigate the oxidative status in infarct rats received curcumin. By using H & E staining, tissue inflammation was performed. Masson’s trichrome staining was conducted to show cardiac remodeling and collagen deposition. The number of apoptotic cells was determined by using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Data showed the serum decrease of LDH, CK, and cTnI in infarct rats after curcumin intake compared to the rats given (ISO) ( P < 0.05). Curcumin was found to reduce oxidative status by reducing SOD and MDA contents ( P < 0.05). Gross and microscopic examinations revealed that the decrease of infarct area, inflammation response and collagen deposition in rats given ISO plus curcumin ( P < 0.05). We noted the superior effect of curcumin to reduce the number of apoptotic cardiomyocytes after 9 days. Data point the cardioprotective effect of curcumin to diminish the complication of infarction by the reduction of cell necrosis and apoptosis in a rat model of experimental infarction.     

Role of thrombin in the pathogenesis of atherosclerosis

Atherosclerosis is an arterial disease associated with inflammation. Thrombin is a procoagulant and proinflammatory serine protease that contributes to the pathology of atherosclerosis by enhancing the expression of cell adhesion molecules, inducing the secretion of proinflammatory cytokines, activating inflammatory responses in atherosclerotic plaques, stimulating proliferation of aortic smooth muscle cells, and exacerbating vascular lesions at sites of injury. Hence, thrombin appears to be an important target for treatment of atherosclerosis and thrombin pharmacological inhibitors have significant therapeutic potency for suppressing inflammatory responses in cardiovascular diseases. This review summarizes the proinflammatory signaling functions of thrombin as well as the therapeutic potency of thrombin inhibitors in the pathogenesis of atherosclerosis and hence their potential therapeutic value in this condition.     

Climate‐driven shifts in the distribution of koala‐browse species from the Last Interglacial to the near future

The koala's Phascolarctos cinereus distribution is currently restricted to eastern and south‐eastern Australia. However, fossil records dating from 70 ± 4 ka (ka = 10³ yr) from south‐western Australia and the Nullarbor Plain are evidence of subpopulation extinctions in the southwest at least after the Last Interglacial (~128–116 ka). We hypothesize that koala sub‐population extinctions resulted from the eastward retraction of the koala's main browse species in response to unsuitable climatic conditions. We further posit a general reduction in the distribution of main koala‐browse trees in the near future in response climate change. We modelled 60 koala‐browse species and constructed a set of correlative species distribution models for five time periods: Last Interglacial (~128–116 ka), Last Glacial Maximum (~23–19 ka), Mid‐Holocene (~7–5 ka), present (interpolations of observed data, representative of 1960–1990), and 2070. We based our projections on five hindcasts and one forecast of climatic variables extracted from WorldClim based on two general circulation models (considering the most pessimistic scenario of high greenhouse‐gas emissions) and topsoil clay fraction. We used 17 dates of koala fossil specimens identified as reliable from 70 (± 4) to 535 (± 49) ka, with the last appearance of koalas at 70 ka in the southwest. The main simulated koala‐browse species were at their greatest modelled extent of suitability during the Last Glacial Maximum, with the greatest loss of koala habitat occurring between the Mid‐Holocene and the present. We predict a similar habitat loss between the present and 2070. The spatial patterns of habitat change support our hypothesis that koala extinctions in the southwest, Nullarbor Plain and central South Australia resulted from the eastward retraction of the dominant koala‐browse species in response to long‐term climate changes. Future climate patterns will likely increase the extinction risk of koalas in their remaining eastern ranges.     

The AMPA receptor subunits GluR-A and GluR-B reciprocally modulate spinal synaptic plasticity and inflammatory pain

Ca(2+)-permeable AMPA receptors are densely expressed in the spinal dorsal horn, but their functional significance in pain processing is not understood. By disrupting the genes encoding GluR-A or GluR-B, we generated mice exhibiting increased or decreased numbers of Ca(2+)-permeable AMPA receptors, respectively. Here, we demonstrate that AMPA receptors are critical determinants of nociceptive plasticity and inflammatory pain. A reduction in the number of Ca(2+)-permeable AMPA receptors and density of AMPA channel currents in spinal neurons of GluR-A-deficient mice is accompanied by a loss of nociceptive plasticity in vitro and a reduction in acute inflammatory hyperalgesia in vivo. In contrast, an increase in spinal Ca(2+)-permeable AMPA receptors in GluR-B-deficient mice facilitated nociceptive plasticity and enhanced long-lasting inflammatory hyperalgesia. Thus, AMPA receptors are not mere determinants of fast synaptic transmission underlying basal pain sensitivity as previously thought, but are critically involved in activity-dependent changes in synaptic processing of nociceptive inputs.     

Bacterial diversity and function of aerobic granules engineered in a sequencing batch reactor for phenol degradation

Aerobic granules are self-immobilized aggregates of microorganisms and represent a relatively new form of cell immobilization developed for biological wastewater treatment. In this study, both culture-based and culture-independent techniques were used to investigate the bacterial diversity and function in aerobic phenol- degrading granules cultivated in a sequencing batch reactor. Denaturing gradient gel electrophoresis (DGGE) analysis of PCR-amplified 16S rRNA genes demonstrated a major shift in the microbial community as the seed sludge developed into granules. Culture isolation and DGGE assays confirmed the dominance of beta-Proteobacteria and high-G+C gram-positive bacteria in the phenol-degrading aerobic granules. Of the 10 phenol-degrading bacterial strains isolated from the granules, strains PG-01, PG-02, and PG-08 possessed 16S rRNA gene sequences that matched the partial sequences of dominant bands in the DGGE fingerprint belonging to the aerobic granules. The numerical dominance of strain PG-01 was confirmed by isolation, DGGE, and in situ hybridization with a strain-specific probe, and key physiological traits possessed by PG-01 that allowed it to outcompete and dominate other microorganisms within the granules were then identified. This strain could be regarded as a functionally dominant strain and may have contributed significantly to phenol degradation in the granules. On the other hand, strain PG-08 had low specific growth rate and low phenol degradation ability but showed a high propensity to autoaggregate. By analyzing the roles played by these two isolates within the aerobic granules, a functional model of the microbial community within the aerobic granules was proposed. This model has important implications for rationalizing the engineering of ecological systems.     

Radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia: it is not always as it is expected

Observation of Coincident arrhythmias is not uncommon but the co-existence of idiopathic verapamil sensitive left ventricular tachycardia (ILVT) with other arrhythmias is very rare. We hereby presented a 30 year old male patient with a history of frequent episodes of palpitations and sustained narrow complex tachycardia. During electrophysiologic study two arrhythmias, one with narrow complexes which was shown to be typical atrioventricular nodal re-entrant tachycardia and the other with wide QRS complexes and right bundle branch block and left axis morphology, compatible with ILVT, were inducible. Radiofrequency catheter ablation of both arrhythmias was done at two consecutive sessions. The patient has remained asymptomatic without antiarrhythmic therapy for the past six months.     

The pesticide rotenone induces caspase-3-mediated apoptosis in ventral mesencephalic dopaminergic neurons

In vivo, the pesticide rotenone induces degeneration of dopamine neurons and parkinsonian-like pathology in adult rats. In the current study, we utilized primary ventral mesencephalic (VM) cultures from E15 rats as an in vitro model to examine the mechanism underlying rotenone-induced death of dopamine neurons. After 11 h of exposure to 30 nm rotenone, the number of dopamine neurons identified by tyrosine hydroxylase (TH) immunostaining declined rapidly with only 23% of the neurons surviving. By contrast, 73% of total cells survived rotenone treatment, indicating that TH+ neurons are more sensitive to rotenone. Examination of the role of apoptosis in TH+ neuron death, revealed that 10 and 30 nm rotenone significantly increased the number of apoptotic TH+ neurons from 7% under control conditions to 38 and 55%, respectively. The increase in apoptotic TH+ neurons correlated with an increase in immunoreactivity for active caspase-3 in TH+ neurons. The caspase-3 inhibitor, DEVD, rescued a significant number of TH+ neurons from rotenone-induced death. Furthermore, this protective effect lasted for at least 32 h post-rotenone and DEVD exposure, indicating lasting neuroprotection achieved with an intervention prior to the death commitment point. Our results show for the first time in primary dopamine neurons that, at low nanomolar concentrations, rotenone induces caspase-3-mediated apoptosis. Understanding the mechanism of rotenone-induced apoptosis in dopamine neurons may contribute to the development of new neuroprotective strategies against Parkinson's disease.     

Identification and comparative analysis of the RpL14 gene from Takifugu rubripes

The ribosomal protein RpL14 gene has been characterized in several species, including, human, rat and fruit fly. Haploinsufficiency for the gene causes the Minute phenotype in Drosophila, and it has been proposed as a regulator in the tumorigenic pathway in human. Several features concerning the gene structure have been studied, and some of these differ between human/rat and Drosophila. To address functional and evolutionary questions about these differences we have isolated and sequenced a cDNA and a genomic clone covering the RpL14 gene from the pufferfish Takifugu rubripes (Fugu). The Fugu RpL14 gene is approximately 2 Kb, with 5 introns, and encodes a protein of 137 amino acids. The protein contains a KOW-motif and a nuclear localization signal, which are conserved among a wide range of RPL14 proteins. On the other hand, a variable amino acid (alanine) repeat observed in human is missing in Takifugu rubripes, and the protein is shorter than its mammalian counterparts. Compared with human, the RpL14 gene in Fugu contains introns localized at identical positions in the gene, and most of them are shorter. A comparison of the RpL14 gene structure from a broad range of organisms indicates that both loss and gain of introns have occurred during the evolution of the gene.