Diode-pumped femtosecond Tm3+-doped LuScO3 laser near 2.1 μm

We report on the first demonstration, to the best of our knowledge, of a diode-pumped Tm:LuScO3 laser. Efficient and broadly tunable continuous wave operation in the 1973–2141 nm region and femtosecond mode-locking through the use of an ion-implanted InGaAsSb quantum-well-based semiconductor saturable absorber mirror are realized. When mode-locked, near-transform-limited pulses as short as 170 fs were generated at 2093 nm with an average output power of 113 mW and a pulse repetition frequency of 115.2 MHz. Tunable picosecond pulse generation was demonstrated in the 2074–2104 nm spectral range

Post-ischaemic silencing of p66Shc reduces ischaemia/reperfusion brain injury and its expression correlates to clinical outcome in stroke

In light of the limited repertoire of therapeutical options available for the treatment of ischaemic stroke, the identification of novel potential targets is vital; in this respect, the present study demonstrates that the adaptor protein p66Shc holds this potential as an adjunct therapy to thrombolysis. Post-ischaemic silencing of p66Shc protein yielded beneficial effects in a mouse model of I/R brain injury underlying an interesting translational perspective for this target protein. Further, in proof-of-principle clinical experiments using PBMs, we demonstrate that p66Shc gene expression is transiently increased and that its levels correlate to short-term outcome in ischaemic stroke patients. Although these latter experiments are not directly relevant to the experiments performed in mice and in human endothelial cells, they provide novel important information about p66Shc regulation in stroke patients and set the basis for further investigations aimed at assessing the potential for p66Shc to become a novel therapeutic target as an adjunct of thrombolysis for the management of acute ischaemic strok

Role of human tissue kallikrein in gastrointestinal stromal tumour invasion

Background: Human tissue kallikrein (hK1) generates vasodilator kinins from kininogen and promotes angiogenesis by kinin-dependent and kinin-independent mechanisms. Here, we investigate the expression and functional relevance of hK1 in human gastrointestinal stromal tumour (GIST).<p></p> Methods: Vascularisation and hK1 expression of GIST samples were assessed by immunohistochemistry. In two GIST cell lines, hK1 expression was assessed by PCR, and hK1 protein levels and activity were measured by ELISA and an amidolytic assay, respectively. The effect of hK1 silencing, inhibition or overexpression on GIST cell proliferation, migration and paracrine induction of angiogenesis was studied. Finally, local and systemic levels of hK1 were assessed in mice injected with GIST cells.<p></p> Results: Human tissue kallikrein was detected in 19 out of 22 human GIST samples. Moreover, GIST cells express and secrete active hK1. Titration of hK1 demonstrated its involvement in GIST invasive behaviour, but not proliferation. Furthermore, hK1 released by GIST cells promoted endothelial cell migration and network formation through kinin-dependent mechanisms. Gastrointestinal stromal tumour implantation in nude mice resulted in local and systemic hK1 expression proportional to tumour dimension.<p></p> Conclusions: Human tissue kallikrein is produced and released by GIST and participates in tumour invasion. Further studies are needed to validate hK1 as a diagnostic biomarker and therapeutic target in GIST

Rapid inflammasome activation is attenuated in post-myocardial infarction monocytes

Inflammasomes are crucial gatekeepers of the immune response, but their maladaptive activation associates with inflammatory pathologies. Besides canonical activation, monocytes can trigger non-transcriptional or rapid inflammasome activation that has not been well defined in the context of acute myocardial infarction (AMI). Rapid transcription-independent inflammasome activation induced by simultaneous TLR priming and triggering stimulus was measured by caspase-1 (CASP1) activity and interleukin release. Both classical and intermediate monocytes from healthy donors exhibited robust CASP1 activation, but only classical monocytes produced high mature interleukin-18 (IL18) release. We also recruited a limited number of coronary artery disease (CAD, n=31) and AMI (n=29) patients to evaluate their inflammasome function and expression profiles. Surprisingly, monocyte subpopulations isolated from blood collected during percutaneous coronary intervention (PCI) from AMI patients presented diminished CASP1 activity and abrogated IL18 release despite increased NLRP3 gene expression. This unexpected attenuated rapid inflammasome activation was accompanied by a significant increase of TNFAIP3 and IRAKM expression. Moreover, TNFAIP3 protein levels of circulating monocytes showed positive correlation with high sensitive troponin T (hsTnT), implying an association between TNFAIP3 upregulation and the severity of tissue injury. We suggest this monocyte attenuation to be a protective phenotype aftermath following a very early inflammatory wave in the ischemic area. Damage-associated molecular patterns (DAMPs) or other signals trigger a transitory negative feedback loop within newly recruited circulating monocytes as a mechanism to reduce post-injury tissue damage

Mid-infrared emission properties of the Tm3+-doped sesquioxide crystals Y2O3, Lu2O3, Sc2O3 and mixed compounds (Y,Lu,Sc)2O3 around 1.5-, 2- and 2.3-μm

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