An excessive, irritable, productive or non-productive coughing
associated with airway inflammation belongs to pathological
cough. Increased activation of airway vagal nociceptors in
pathological conditions results from dysregulation of the neural
pathway that controls cough. A variety of mediators associated
with airway inflammation overstimulate these vagal airway fibers
including C-fibers leading to hypersensitivity and hyperreactivity.
Because current antitussives have limited efficacy and unwanted
side effects there is a continual demand for the development of
a novel more effective antitussives for a new efficacious and safe
cough treatment. Therefore, inhibiting the activity of these vagal
C-fibers represents a rational approach to the development of
effective antitussive drugs. This may be achieved by blocking
inflammatory mediator receptors or by blocking the generator
potential associated with the specific ion channels. Because
voltage-gated sodium channels (NaVs) are absolutely required for
action potentials initiation and conduction irrespective of the
stimulus, NaVs become a promising neural target. There is
evidence that NaV1.7, 1.8 and 1.9 subtypes are predominantly
expressed in airway cough-triggering nerves. The advantage of
blocking these NaVs is suppressing C-fiber irrespective to stimuli,
but the disadvantage is that by suppressing the nerves is may
also block beneficial sensations and neuronal reflex behavior. The
concept is that new antitussive drugs would have the benefit of
targeting peripheral airway nociceptors without inhibiting the
protective cough reflex.
Mangiferin is a kind of polyphenol chemical compound separated from these herbal medicines of Mangifera indica L., Anemarrhena asphodeloides Bge. and Belamcanda chinensis L., which has anti-inflammatory, anti-virus, and other physiological activities without toxic effects. Osteoarthritis (OA) is a chronic disease that is also a kind of arthritis disease in which articular cartilage or bones under the joint is damaged. In addition, artificial replacements are required in severe cases. At present, there are not too much researches on the potential biological activities of mangiferin that plays a protective role in the treatment of OA. In this study, we evaluated the protective effect of mangiferin on osteoarthritis (OA) in vitro and in vivo. First, the effect of different concentrations of mangiferin on rat chondrocytes was determined by MTT assay. Second, the effects of mangiferin on the expression levels of matrix metalloproteinase (MMP)-13, TNF-α, Collagen II, Caspase-3, and cystatin-C in interleukin-1β (IL-1β)-induced rat chondrocytes were examined by the real-time polymerase chain reaction in vitro, meanwhile the effects of mangiferin on the nuclear factor kappa-B (NF-κB) signaling pathway were also investigated by Western Blot. Finally, the antiosteoarthritic protective effect of mangiferin was evaluated in the rat model by anterior cruciate ligament transection (ACLT) combined with bilateral ovariectomy-induced OA in vivo. The results showed that the mangiferin was found to inhibit the expression of MMP-13, TNF-α, and Caspase-3 which also increased the expression of Collagen II and cystatin-C in IL-1β-induced rat chondrocytes. In addition, IL-1β-induced activation of nuclear factor kappa-B (NF-κB) and the degradation of inhibitor of κB (IκB)-α were suppressed by mangiferin. For the in vivo study in a rat model of OA, 100 μl of mangiferin was administered by intra-articular injections for rats, the results showed that the cartilage degradation was suppressed by mangiferin through Micro CT and Histological Examination. According to both in vitro and in vivo results, mangiferin has a protective effect in the treatment of OA which may be a promising therapeutic agent for OA.
A survey of the species of the Proteocephalus-aggregate from sticklebacks (Actinopterygii: Gasterosteidae) is provided. The occurrence of three species in North America is confirmed: (i) Proteocephalus filicollis (Rudolphi, 1802), which has been reported from the three-spined stickleback, Gasterosteus aculeatus Linnaeus, in the northeastern part of North America (Newfoundland); (ii) Proteocephalus pugetensis Hoff et Hoff, 1929 occurs also in G. aculeatus, but in northwestern North America (British Columbia and Washington); and (iii) Proteocephalus culaeae sp. n., which is described from the brook stickleback, Culaea inconstans (Kirtland), in Manitoba (Canada). Another species, Proteocephalus ambiguus (Dujardin, 1845), a specific parasite of the nine-spined stickleback, Pungitius pungitius (Linnaeus), and type species of the genus, has also been found in North America (Alberta, Canada), but its vouchers are in poor condition and cannot be reliable assigned to this species. Both species reported from three-spined stickleback differ from each other by the shape of the scolex (rounded in P. filicollis versus continuously tapered towards the anterior extremity in P. pugetensis) and the apical sucker (widely oval to subspherical in frontal view in P. filicollis versus flattened in P. pugetensis). Proteocephalus culaeae sp. n. is characterised by a short body composed of a few, continuously widened proglottids, a short scolex narrower than the strobila and devoid of an apical sucker, a short, pyriform cirrus sac, no vaginal sphincter, and few testes. A key to species of the Proteocephalus-aggregate from sticklebacks is provided.
L-arginine is a substrate for nitric oxide synthase (NOS) responsible for the production of NO. This investigation studied the effect of apocynin, an NADPH oxidase inhibitor and catalase, an H2O2 scavenger on L-arginine-induced oxidative stress and hypotension. Forty Wistar-Kyoto rats were treated for 14 days with vehicle, L-arginine (12.5 mg/ml p.o.), L-arginine + apocynin (2.5 mmol/l p.o.), L-arginine + catalase (10000 U/kg/day i.p.) and L-arginine plus apocynin + catalase respectively. Weekly renal functional and hemodynamic parameters were measured and kidneys harvested at the end of the study for histopathological and renal NADPH oxidase 4 (Nox4) assessments. L-arginine administration in normotensive rats decreased systolic blood pressure (120±2 vs. 91±2 mmHg) and heart rate (298±21 vs. 254±15 bpm), enhanced urinary output (21.5±4.2 vs. 32±1.9 ml/24 h, increased creatinine clearance (1.72±0.56 vs. 2.62±0.40 ml/min/kg), and fractional sodium excretion (0.88±0.16 vs. 1.18±0.16 %), caused proteinuria (28.10±1.93 vs. 35.26±1.69 mg/kg/day) and a significant decrease in renal cortical blood perfusion (292±3 vs. 258±5 bpu) and pulse wave velocity (3.72±0.20 vs 2.84±0.13 m/s) (all P<0.05). L-arginine increased plasma malondialdehyde (by ~206 % P<0.05) and NO (by ~51 %, P<0.05) but decreased superoxide dismutase (by ~31 %, P<0.05) and total antioxidant capacity (by ~35 %, P<0.05) compared to control. Renal Nox4 mRNA activity was approximately 2.1 fold higher (P<0.05) in the L-arginine-treated rats but was normalized by apocynin and apocynin plus catalase treatment. Administration of apocynin and catalase, but not catalase alone to rats fed L-arginine, restored the deranged renal function and structure, prevented hypotension and enhanced the antioxidant capacity and suppressed Nox4 expression. These findings suggest that apocynin and catalase might be used prophylactically in the states of oxidative stress.
Although playing an important role in shaping the environment, the mechanisms responsible for runoff initiation and yield in arid and semiarid regions are not yet fully explored. With infiltration-excess overland flow, known also as Hortonian overland flow (HOF) taking place in these areas, the uppermost surface 'skin' plays a cardinal role in runoff initiation and yield. Over large areas, this skin is composed of biocrusts, a variety of autotrophs (principally cyanobacteria, green algae, lichens, mosses) accompanied by heterotrophs (such as fungi, bacteria, archaea), which may largely dictate the infiltration capability of the surface. With most biocrust organisms being capable of excreting extracellular polymeric substances (EPS or exopolymers), and growing evidence pointing to the capability of certain EPS to partially seal the surface, EPS may play a cardinal role in hindering infiltration and triggering HOF. Yet, despite this logic thread, great controversy still exists regarding the main mechanisms responsible for runoff generation (runoff initiation and yield). Elucidation of the possible role played by EPS in runoff generation is the focus of the current review.
The common pistachio psyllid (CPP) is thought to respond to nutrient availability in pistachio trees. We determined the effect of a deficiency of leaf iron (Fe) has on the abundance of the pistachio psyllid at a regional scale. First, we monitored the abundance pistachio psyllid in four pistachio orchards (24 trees as 24 repetitions) located in Maybod County, Yazd province in the centre of Iran and then measured leaf nutrient levels. Orchards were located up to 2.6 km apart. Multivariate regressions were used to determine the relationship between leaf nutrients and CPP population growth. The results indicate that the number of psyllid eggs and population growth rate of the nymphs was negatively correlated with Fe levels in the leaves, while peak numbers of psyllid eggs were positively correlated with the levels of Cu in the leaves. In a manipulative field experiment, we conducted two experiments: (1) pistachio trees treated with iron compared with control trees, and (2) pistachio trees previously treated with iron were treated with ammonium sulphate and compared with trees treated with ammonium sulphate. In the first experiment, psyllids in leaf disc-cages had a significantly greater intrinsic rate of population increase and net reproductive rate on Fe-treated trees than the control trees (Stage 1). In the second experiment, psyllids in leaf disc-cages had similar intrinsic rates of population increase and net reproduction both on the ammonium sulphate treated trees (control) and those previously treated with iron. This indicates that iron may have reacted negatively with nitrogen content of the leaves. In general, these findings indicate that when there is a deficiency of iron in the leaves, the application of nitrogen fertilizer had little effect on the performance of CPP and may have played a minor role in the population dynamics of CPP, but the application of a Fe fertilizer without considering the nitrogen content of the leaves may lead to a population outbreak.
Coprophagous insect communities play a critical role in the decomposition of vertebrate dung and provide ecosystem
functions fundamental to modern agriculture. While the ecology of dung beetles is rather well understood, niche differentiation in
coprophagous fl ies is poorly studied. Sepsid fl ies (Diptera: Sepsidae) are a vital part of the European community of coprophages,
with 6–7 widespread species of Sepsis often found co-occurring in the same pasture. To advance our ecological understanding of
the mechanisms that enable species to coexist, we investigated the oviposition preferences and larval performance of 7 common
species of Sepsis in the dung of different large domestic and wild mammals. Substrate preferences and subsequent performance
of larvae in laboratory experiments did not vary greatly. All species did very well on cow dung, the most common substrate in
Central Europe, but also on dung of horse and wild boar. In contrast, fl ies did not prefer or grow well in dung of red and roe deer,
two of the most common wild vertebrates. Thus there were only minor differences among the species tested along the specialistgeneralist (dung) gradient, indicating that differences in the choice of oviposition sites by the adults of the different fl y species
and larval performance do not constitute a major axis of ecological differentiation. Nevertheless, there was a positive correlation
between substrate choice and larval performance indicating the preference of gravid females for particular oviposition sites is
adaptive. We conclude that sepsids are common in Europe because they are well adapted to the dung of herbivorous livestock
rather than wild animals. Nevertheless, specialization on particular types of dung does not defi ne the niche of Sepsis dung fl ies
and hence plays a minor role in mediating their species diversity.
Reactive oxygen species are an important element of redox regulation in cells and tissues. During physiological processes, molecules undergo chemical changes caused by reduction and oxidation reactions. Free radicals are involved in interactions with other molecules, leading to oxidative stress. Oxidative stress works two ways depending on the levels of oxidizing agents and products. Excessive action of oxidizing agents damages biomolecules, while a moderate physiological level of oxidative stress (oxidative eustress) is necessary to control life processes through redox signaling required for normal cellular operation. High levels of reactive oxygen species (ROS) mediate pathological changes. Oxidative stress helps to regulate cellular phenotypes in physiological and pathological conditions. Nrf2 (nuclear factor erythroid 2-related factor 2, NFE2L2) transcription factor functions as a target nuclear receptor against oxidative stress and is a key factor in redox regulation in hypertension and cardiovascular disease. Nrf2 mediates transcriptional regulation of a variety of target genes. The Keap1-Nrf2-ARE system regulates many detoxification and antioxidant enzymes in cells after the exposure to reactive oxygen species and electrophiles. Activation of Nrf2/ARE signaling is differentially regulated during acute and chronic stress. and Keap1 normally maintains Nrf2 in the cytosol and stimulates its degradation through ubiquitination. During acute oxidative stress, oxidized molecules modify the interaction of Nrf2 and Keap1, when Nrf2 is released from the cytoplasm into the nucleus where it binds to the antioxidant response element (ARE). This triggers the expression of antioxidant and detoxification genes. The consequence of long-term chronic oxidative stress is activation of glycogen synthase kinase 3β (GSK-3β) inhibiting Nrf2 activity and function. PPARγ (peroxisome proliferator-activated receptor gamma) is a nuclear receptor playing an important role in the management of cardiovascular diseases, hypertension and metabolic syndrome. PPARγ targeting of genes with peroxisome proliferator response element (PPRE) has led to the identification of several genes involved in lipid metabolism or oxidative stress. PPARγ stimulation is triggered by endogenous and exogenous ligands – agonists and it is involved in the activation of several cellular signaling pathways involved in oxidative stress response, such as the PI3K/Akt/NOS pathway. Nrf2 and PPARγ are linked together with their several activators and Nrf2/ARE and PPARγ/PPRE pathways can control several types of diseases.
Flagellin (flg22) induces rapid and long-lasting defence responses. It may also affect the photosynthetic activity depending on several internal and external factors, such as the phytohormone ethylene or the day/night time. Based on the results, flg22 treatment, neither in the light phase nor in the evening, caused any significant change in chlorophyll fluorescence induction parameters in the leaves of wild-type and ethylene-receptor mutant Never ripe tomato plants measured the next morning. However, flg22 in the light phase decreased the effective quantum yield and the photochemical quenching both locally and systemically in guard cells. In parallel, the production of reactive oxygen species and nitric oxide increased, which contributed to the stomatal closure and a decrease in CO2 assimilation the next day. A decrease in sugar content and elevated hexokinase activity measured after flg22 exposure can also contribute to local defence responses in intact tomato plants.
Atrial fibrillation and atrial tachycardias (AF/AT) have been reported as a common condition in patients with pulmonary hypertension (PH). As yet, limited data exists about the significance of the borderline post-capillary pressure component on the occurrence of AF / AT in patients with isolated pre-capillary PH. We retrospectively studied the prevalence of AF / AT in 333 patients (mean age 61±15 years, 44 % males) with pre-capillary idiopathic / familiar pulmonary arterial hypertension, and inoperable chronic thromboembolic pulmonary hypertension. The prevalence of AF / AT was analyzed in different categories of pulmonary artery wedge pressure (PAWP). In the study population overall, the mean PAWP was 10.5±3 mmHg, median of 11 mmHg, range 2-15 mmHg. AF / AT was diagnosed in 79 patients (24 %). The proportion of AF / AT among patients with PAWP below the median (≤11 mmHg) was lower than in subjects with PAWP between 12 and 15 mmHg, 30 (16 %) vs. 46 (35 %), p=0.0001. Compared to the patients with PAWP≤11 mmHg, subjects with PAWP between 12 and 15 mmHg were older (65±13 years vs. 58±16), with more prevalent arterial hypertension [100 (70 %) vs. 106 (55 %)] and diabetes mellitus [50 (35 %) vs. 48 (25 %)], showed larger size of the left atrium (42±7 vs. 40±6 mm), and higher values of right atrium pressure (12±5 vs. 8±5 mmHg), p<0.05 in all comparisons. The prevalence of AF / AT in the group studied increased with the growing post-capillary component.