Paracrine control of tissue regeneration and cell proliferation by Caspase-3

Executioner caspases such as Caspase-3 and Caspase-7 have long been recognised as the key proteases involved in cell demolition during apoptosis. Caspase activation also modulates signal transduction inside cells, through activation or inactivation of kinases, phosphatases and other signalling molecules. Interestingly, a series of recent studies have demonstrated that caspase activation may also influence signal transduction and gene expression changes in neighbouring cells that themselves did not activate caspases. This review describes the physiological relevance of paracrine Caspase-3 signalling for developmental processes, tissue homeostasis and tissue regeneration, and discusses the role of soluble factors and microparticles in mediating these paracrine activities. While non-cell autonomous control of tissue regeneration by Caspase-3 may represent an important process for maintaining tissue homeostasis, it may limit the efficiency of current cancer therapy by promoting cell proliferation in those cancer cells resistant to radio- or chemotherapy. We discuss recent evidence in support of such a role for Caspase-3, and discuss its therapeutic implication.     

A mutation in the cytosolic O-acetylserine (thiol) lyase induces a genome-dependent early leaf death phenotype in <Emphasis Type="Italic">Arabidopsis</Emphasis>

Background  

Cysteine is a component in organic compounds including glutathione that have been implicated in the adaptation of plants to stresses. O-acetylserine (thiol) lyase (OAS-TL) catalyses the final step of cysteine biosynthesis. OAS-TL enzyme isoforms are localised in the cytoplasm, the plastids and mitochondria but the contribution of individual OAS-TL isoforms to plant sulphur metabolism has not yet been fully clarified.     

Flat Feet,Happy Feet? Comparison of the Dynamic Plantar Pressure Distribution and Static Medial Foot Geometry between Malawian and Dutch Adults

In contrast to western countries, foot complaints are rare in Africa. This is remarkable, as many African adults walk many hours each day, often barefoot or with worn-out shoes. The reason why Africans can withstand such loading without developing foot complaints might be related to the way the foot is loaded. Therefore, static foot geometry and dynamic plantar pressure distribution of 77 adults from Malawi were compared to 77 adults from the Netherlands. None of the subjects had a history of foot complaints. The plantar pressure pattern as well as the Arch Index (AI) and the trajectory of the center of pressure during the stance phase were calculated and compared between both groups. Standardized pictures were taken from the feet to assess the height of the Medial Longitudinal Arch (MLA). We found that Malawian adults: (1) loaded the midfoot for a longer and the forefoot for a shorter period during roll off, (2) had significantly lower plantar pressures under the heel and a part of the forefoot, and (3) had a larger AI and a lower MLA compared to the Dutch. These findings demonstrate that differences in static foot geometry, foot loading, and roll off technique exist between the two groups. The advantage of the foot loading pattern as shown by the Malawian group is that the plantar pressure is distributed more equally over the foot. This might prevent foot complaints.     

Seropositivity for CMV and IL-6 levels are associated with grip strength and muscle size in the elderly

Background

Sarcopenia is an important cause of morbidity and mortality in older adults, with immunosenescence and inflammation being possible underlying mechanisms. We investigated the relationship between latent cytomegalovirus (CMV) infection, Interleukin 6 (IL-6) levels, muscle size and strength in a group of healthy older community-dwelling people.

Methods

Participants were healthy volunteers from the Lothian Birth Cohort 1936 study. Participants had IL-6 level and CMV antibody titre measured at age 70 years and grip strength and a volumetric T1-weighted MRI brain scan (allowing measurement of neck muscle cross-sectional area (CSA)) at age 73. Markers of childhood deprivation were adjusted for in the analysis due to correlations between childhood deprivation and latent CMV infection.

Results

866 participants were studied; 448 men (mean age 72.48 years, sd 0.70) and 418 women (mean age 72.51 years, sd 0.72). In men, CMV seropositivity was associated with smaller neck muscle CSA (p = 0.03, partial eta squared = 0.01), even after adjustment for IL-6 levels. Neck muscle CSA was not associated with CMV seropositivity in women, or CMV antibody titre or IL-6 level in either sex. Grip strength associated negatively with IL-6 level (right grip strength p<0.00001, partial eta squared 0.032 and left grip strength p<0.00001, partial eta squared 0.027) with or without adjustment for CMV serostatus or antibody titre. CMV status and antibody titre were not significantly associated with grip strength in either hand.

Conclusion

These findings support the hypothesis that there is a relationship between markers of immunosenescence (i.e. CMV serostatus and IL6 level) and low muscle mass and strength and longitudinal studies in older cohorts are now required to investigate these relationships further.

     

Alpha-lipoic acid rebalances redox and immune-testicular milieu in septic rats

In the present study, lipopolysaccharide (LPS), as an immune modulator in male adult rats and alpha-lipoic acid (ALA), as a powerful biological antioxidant and anti-inflammatory, are examined to help understanding the role of the immune and redox perturbation in testicular dysfunction with a possible protection. A total of 60 male Swiss albino rats were divided into 5 groups (10/group) respectively as follows Saline, ALA-vehicle, ALA (200 mg/kg), LPS (5 mg/kg) started with 20 rats and LPS + ALA. Obtained data from previously reported study, in our laboratory, and from the present one revealed that LPS induced marked reductions in sperm's count, motility and resulted in deterioration of the testicular histological features. In addition, LPS decreased testicular reduced glutathione (GSH) level and lactate dehydrogenase isoenzyme-x (LDH-x) activity. However, it increased testicular levels of malondialdehyde (MDA), nitric oxide (NO) and 8-hydroxydeoxyguanosine (8-HDG) in testicular DNA, along with increased serum IL-2 level. In contrast, rats pretreated with ALA showed almost complete normalization of all the tested parameters. In conclusion, LPS induced perturbation of the immune-testicular barrier as a result of redox imbalance with a subsequent testicular dysfunction. Pretreatment with ALA ameliorated all these effects by its immune-modulator and antioxidant mechanisms suggesting a protective role against male infertility in septic or severely infected patients.     

Molecular screening of Chinese medicinal plants for progestogenic and anti-progestogenic activity

Estrogen and progestins have adverse effects, and many of these adverse effects are caused by progestins. Due to this, many women choose to use botanical alternatives for hormone replacement therapy, which does not trigger steroidogenic properties. Therefore, it is necessary to screen these herbs for progestogenic and anti-progestogenic properties. Extract of 13 Chinese medicinal plants were analysed for progestogenic and anti-progestogenic activities by using progesterone response element-driven luciferase reporter gene bioassay. MTT assay was carried out to investigate the cytotoxic effect of herb extract on PAE cells. Among the 13 herbs, Dipsacus asperoides extract exhibited progestogenic activity, and 10 species – Cortex eucommiae, Folium artemisiae argyi, Glycyrrhiza uralensis, Angelica sinensis, Atractylodes macrocephala koidz, Scutellaria baicalensis, Cuscuta chinensis, Euscaphis japonica, Ailanthus altissima, and Dioscorea opposita – were recognized to have anti-progestogenic like activities. Extract of Dipsacus asperoides demonstrated dose-dependent progestogenic activity, and the progestogenic activity of 100 μg/mL extracts was equivalent to 31.45 ng/mL progesterone activity. Herbs extracts that exhibited anti-progestogenic-like activity also inhibited the 314.46 ng/mL progesterone activity in a dose-response manner. None of the herb extracts shown significant toxic effect on PAE cells at 40–100 μg/mL compared to control. This discovery will aid selection of suitable herbs for hormone replacement therapy.     

Thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of IL-8 expression,elevated levels of TRAIL receptors,oxidative stress and apoptosis

Sod2 is the major salt tolerance plasma membrane protein of Schizosaccharomyces pombe. It functions to remove excess intracellular sodium (or lithium) in exchange for protons. We investigated the role of cysteine residues and created a cysteine-free Sod2 protein. Each cysteine residue of the ten present was individually mutated to serine and the different proteins expressed and characterized in S. pombe. Western blotting revealed that all the individual mutant proteins were expressed. We examined the ability of the mutant proteins to confer salt tolerance to S. pombe with the endogenous Sod2 protein deleted. Only proteins with C26S and C374S mutations were partially reduced in their ability to confer salt tolerance. Additionally, they showed a change in conformation in comparison to the wild-type protein, indicated by differential sensitivity to trypsin. Deletion of all the cysteine residues of Sod2 resulted in a functional protein that was expressed in S. pombe at levels similar to the wild type and also conferred salt tolerance. The conformation of the cysteine-free Sod2 protein was not altered relative to the wild-type protein. We examined the accessibility of amino acids of the cysteineless protein present on putative extracellular loop 2. A cysteine placed at position Ala119 was accessible to externally applied [2-(trimethylammonium)ethyl] methane thiosulfonate bromide. The results demonstrate that cysteines in the Sod2 protein can be changed to serine residues resulting in an expressed, functional protein. The utility of the cysteine-free Sod2 protein for determination of topology and amino acid accessibility is demonstrated.     

Wirkung von Deoxynivalenol beim wachsenden Schwein in Abhängigkeit von der Darreichungsform

To evaluate the minimum effective dose of pure DON leading to measurable losses in weight gain and feed consumption a special feeding experiment was created to compare the effect of DON in natural contaminated wheat and — for the first time — a non-cereal diet (potato) spiked with pure DON. Examined parameters were weight gain, feed consumption and blood parameters.Three trials were conducted. In the first trial a concentration of 4000 µg DON/kg feed was used. In the second and third trial we used concentrations of 4000 and 6000 µg DON/kg feed. Severe effects on feed consumption and weight gain were found only in the second trial (naturally contaminated wheat ad lib.). By contrast, no differences in any parameter were found in the first (restricted feeding) and third trial (non-cereal diet spiked with pure DON ad lib.).