Phytochemicals from the stem wood of Sorbus lanata (D. Don.) Schauer

Three new phenolic compounds, sorlanin (4-(3-(hydroxymethyl)-5-methoxy-7-phenyl-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)-2-methoxyphenol, 1), sorbanin (2-((3,5-dimethoxy-[1,1′-biphenyl]-4-yl)oxy)-1-(4-hydroxy-3-methoxyphenyl)propane-1,3-diol, 2) and sorbalanin (4-(3-(hydroxymethyl)-5,6-dimethoxy-2,3-dihydrobenzo[b][1,4]dioxino[2,3-g]benzofuran-2-yl)-2-methoxyphenol, 3), together with eight known compounds, polystachyol (4), isolariciresinol (5), dihydrodehydrodiconiferyl alcohol (6), tuberculatin (7), ovafolinin E (8), aucuparin (9), 2′-methoxyaucuparin (10), and tetracosyl-3-(3,4-dihydroxyphenyl)acrylate (11), were isolated from Sorbus lanata. The structures of these phytoconstituents were elucidated through extensive spectroscopic techniques, including UV, IR, 1D and 2D NMR, ESI-MS and HRESI-MS experiments. All the compounds except 9 and 10 were isolated for the first time from the genus Sorbus. The isolated compounds were also tested in DPPH radical scavenging reaction where compounds 6, 7, 10 and 11 showed significant activities with IC₅₀ values of 9.2, 11.7, 23.0 and 33.7 μM, respectively.     

Familial hemiplegic migraine mutations affect Na,K-ATPase domain interactions

Familial hemiplegic migraine (FHM) is a monogenic variant of migraine with aura. One of the three known causative genes, ATP1A2, which encodes the α2 isoform of Na,K-ATPase, causes FHM type 2 (FHM2). Over 50 FHM2 mutations have been reported, but most have not been characterized functionally. Here we study the molecular mechanism of Na,K-ATPase α2 missense mutations. Mutants E700K and P786L inactivate or strongly reduce enzyme activity. Glutamic acid 700 is located in the phosphorylation (P) domain and the mutation most likely disrupts the salt bridge with Lysine 35, thereby destabilizing the interaction with the actuator (A) domain. Mutants G900R and E902K are present in the extracellular loop at the interface of the α and β subunit. Both mutants likely hamper the interaction between these subunits and thereby decrease enzyme activity. Mutants E174K, R548C and R548H reduce the Na⁺ and increase the K⁺ affinity. Glutamic acid 174 is present in the A domain and might form a salt bridge with Lysine 432 in the nucleotide binding (N) domain, whereas Arginine 548, which is located in the N domain, forms a salt bridge with Glutamine 219 in the A domain. In the catalytic cycle, the interactions of the A and N domains affect the K⁺ and Na⁺ affinities, as observed with these mutants. Functional consequences were not observed for ATP1A2 mutations found in two sporadic hemiplegic migraine cases (Y9N and R879Q) and in migraine without aura (R51H and C702Y).     

Melatonin inhibits Gram-negative pathogens by targeting citrate synthase

Bacterial infections caused by Gram-negative pathogens represent a growing burden for public health worldwide. Despite the urgent need for new antibiotics that effectively fight against pathogenic bacteria, very few compounds are currently under development or approved in the clinical setting. Repurposing compounds for other uses offers a productive strategy for the development of new antibiotics. Here we report that the multifaceted melatonin effectively improves survival rates of mice and decreases bacterial loads in the lung during infection. Mechanistically, melatonin specifically inhibits the activity of citrate synthase of Gram-negative pathogens through directly binding to the R300, D363, and H265 sites, particularly for the notorious Pasteurella multocida. These findings highlight that usage of melatonin is a feasible and alternative therapy to tackle the increasing threat of Gram-negative pathogen infections via disrupting metabolic flux of bacteria.

     

Iron chelation or anti-oxidants prevent renal cell damage in the rewarming phase after normoxic, but not hypoxic cold incubation

It has now been firmly established that, not only ischemia/reperfusion, but also cold itself causes damage during kidney transplantation. Iron chelators or anti-oxidants applied during the cold plus rewarming phase are able to prevent this damage. At present, it is unknown if these measures act only during the cold, or whether application during the rewarming phase also prevents damage. We aimed to study this after cold normoxic and hypoxic conditions. LLC-PK1 cells were incubated at 4 degrees C in Krebs-Henseleit buffer for 6 or 24h, followed by 18 or 6h rewarming, respectively. Cold preservation was performed under both normoxic (95% air/5% CO2) and hypoxic (95% N2/5% CO2) conditions. The iron chelator 2,2'-DPD (100 microM), anti-oxidants BHT (20 microM) or sibilinin (200 microM), and xanthine oxidase inhibitor allopurinol (100 microM) were added during either cold preservation plus rewarming, or rewarming alone. Cell damage was assessed by LDH release (n=3-9). Addition of 2,2'-DPD and BHT during cold hypoxia plus rewarming did, but during rewarming alone did not prevent cell damage. When added during rewarming after 6h cold normoxic incubation, BHT and 2,2'-DPD inhibited rewarming injury compared to control (p<0.05). Allopurinol did not prevent cell damage in any experimental set-up. Our data show that application of iron chelators or anti-oxidants during the rewarming phase protects cells after normoxic but not hypoxic incubation. Allopurinol had no effect. Since kidneys are hypoxic during transplantation, measures aimed at preventing cold-induced and rewarming injury should be taken during the cold.     

Birth defects interstate data exchange: a battle worth fighting?

BACKGROUND: Regardless of where infants and children are delivered, diagnosed, or treated, an important aspect of population-based birth defects surveillance is ensuring the inclusion of children with birth defects in the catchment area. However, little is known as to how the lack of interstate birth defects data exchange affects program surveillance, monitoring, prevention, and referral activities. The study objectives were to determine the status of interstate birth defects data exchange agreements and to quantify statewide data on resident births occurring in nonresident states. METHODS: In 2004, surveys were distributed to all population-based birth defects programs in the United States to determine: 1) the types of interstate birth defects data exchange agreements that exist among birth defects programs, 2) perceived barriers in establishing exchange agreements, and 3) the extent to which out-of-state births affect a program's catchment area. The National Center for Health Statistics (NCHS) data for 2002 on live birth residency were used to determine the actual frequency of out-of-state live birth occurrence. RESULTS: Of the 52 states and territories that were surveyed, 65% (n = 34) responded. Approximately 21% (n = 7) of those that responded had an interstate data exchange agreement that allowed sharing of birth defects data with another state or a facility within another state. Approximately 53% (n = 18) of responding states indicated plans to develop an interstate birth defects data exchange agreement with other states, hospitals, or both. The NCHS data showed that the actual percentage of resident out-of-state live births ranged from 0.16 to 11.51. NCHS data also reveal that 78% of states would be able to capture >75% of their out-of-state births by sharing data on out-of-state births with the three neighboring states ranking highest in terms of such occurrences. CONCLUSIONS: Few states have interstate birth defects data exchange agreements, though all states have resident births occurring out of state. While suggestive, data beyond residency of live births are needed to quantify the degree to which the objectives of state-based birth defects programs are compromised. Resources exist to guide programs in establishing interstate data exchange agreements. Efforts to establish such agreements with only a few neighboring states could be a large step toward improving birth defects surveillance on a state, regional, and national level.     

Potential use of melatonin in skin cancer treatment: A review of current biological evidence

Skin cancer, particularly melanoma, is a leading cause of death worldwide. The therapeutic methods for this malignancy are not effective, and due to the side effects of these treatments, applying an appropriate alternative or complementary treatment is important. According to available data, melatonin as the main product of the pineal gland has oncostatic and antitumoral properties. Also, melatonin acts as an anti-inflammatory and reactive oxygen species inducer agent which suppresses the growth of tumors. It also has apoptosis induction characteristics through regulating signaling pathways, including heat shock protein 70, nuclear factor-erythroid 2 p45-related factor 2 and others. Thus, adding melatonin to chemo- and radiotherapy may have synergistic therapeutic effects and increase the survival time in patients with skin cancer. Few clinical studies have evaluated the efficacy of melatonin in skin cancer. Based on the related mechanisms, this review discusses about how melatonin may improve outcomes in skin cancer patients.     

Melatonin,a toll-like receptor inhibitor: Current status and future perspectives

Toll-like receptors (TLRs) are crucial activators of inflammatory responses, they are considered immune receptors. TLRs are of fundamental importance in the pathophysiology of disorders related to inflammation including neurodegenerative diseases and cancer. Melatonin is a beneficial agent in the treatment of inflammatory and immune disorders. Melatonin is potent anti-inflammatory hormone that regulates various molecular pathways. Withal, limited studies have evaluated the inhibitory role of melatonin on TLRs. This review summarizes the current knowledge related to the effects of melatonin on TLRs in some common inflammatory and immunity disorders.     

Melatonin is an appropriate candidate for breast cancer treatment: Based on known molecular mechanisms

Breast cancer is the most prevalent cancer and one of the most important causes of death in women throughout the world. Breast cancer risk factors include smoking, alcohol consumption, personal and family history, hypertension, and hormone therapy, long-term use of nonsteroidal anti-inflammatory drugs and tobacco usage. Surgery, chemotherapy, radiotherapy, immunotherapy, and neoadjuvant therapy are the current means for breast cancer treatment. Despite hormonal agents and chemotherapy, which have beneficial effects on lowering breast cancer death rate, the reaction of different people to these treatments is still a challenging point. Melatonin (N-acetyl-5-methoxy tryptamine) is a methoxy indole compound that is mainly secreted by the pineal gland at night; it is as an antioxidant, anti-inflammatory, and oncostatic agent. On the basis of recent studies, melatonin has antitumor properties on different cancer types and it may suppress cancer development in vitro and as well as in animal models. It is suggested that melatonin inhibits the development of breast cancer by various mechanisms. This paper summarizes the roles of melatonin in breast cancer treatment from the aspect of its molecular actions.     

Indices of environmental temperatures for primates in open habitats

Studies of thermoregulation in primates are under-represented in the literature, although there is sufficient evidence to suggest that temperature represents an important ecological constraint. One of the problems in examining thermoregulation in primates, however, is the difficulty in quantifying the thermal environment, since shade temperatures, solar radiation, humidity and wind speed all serve to alter an animals perceived temperature. Since animals respond to their perceived temperature, we need methods to account for each of these factors, both individually and collectively, if we are to understand the integrated impact of the thermal environment on primates. Here, we present a review of some thermal indices currently available. Black bulb temperatures can account for the effect of solar radiation, with wind chill equivalent temperatures and the heat index providing quantifiable estimates of the relative impact of wind speed and humidity, respectively. We present three potential indices of the perceived environmental temperature (PET) that account for the combined impact of solar radiation, humidity and wind speed on temperature, and perform a preliminary test of all of the climatic indices against behavioural data from a field study of chacma baboons (Papio cynocephalus ursinus) at De Hoop Nature Reserve, South Africa. One measure of the perceived environmental temperature, PET2, is an effective thermal index, since it enters the models for feeding and resting behaviour, and also accounts for levels of allogrooming. Solar radiation intensity is an important factor underlying these relationships, although the wind chill equivalent temperature and humidity enter the models for other behaviours. Future studies should thus be mindful of the impact of each of these elements of the thermal environment. A detailed understanding of primate thermoregulation will only come with the development of biophysical models of the thermal characteristics of the species and its environment. Until such developments, however, the indices presented here should permit a more detailed examination of the thermal environment, allowing thermoregulation to be given greater precedence in future studies of primate behaviour.     

Biotelemetry: a mechanistic approach to ecology

Remote measurement of the physiology, behaviour and energetic status of free-living animals is made possible by a variety of techniques that we refer to collectively as 'biotelemetry'. This set of tools ranges from transmitters that send their signals to receivers up to a few kilometers away to those that send data to orbiting satellites and, more frequently, to devices that log data. They enable researchers to document, for long uninterrupted periods, how undisturbed organisms interact with each other and their environment in real time. In spite of advances enabling the monitoring of many physiological and behavioural variables across a range of taxa of various sizes, these devices have yet to be embraced widely by the ecological community. Our review suggests that this technology has immense potential for research in basic and applied animal ecology. Efforts to incorporate biotelemetry into broader ecological research programs should yield novel information that has been challenging to collect historically from free-ranging animals in their natural environments. Examples of research that would benefit from biotelemetry include the assessment of animal responses to different anthropogenic perturbations and the development of life-time energy budgets.