Presenting Psychiatric and Neurological Symptoms and Signs of Brain Tumors before Diagnosis: A Systematic Review

Brain tumors can present with various psychiatric symptoms, with or without neurological symptoms, an aspect that complicates the clinical picture. However, no systematic description of symptoms that should prompt a neurological investigation has been provided. This review aims to summarize available case reports describing patients with brain tumors showing psychiatric symptoms before brain tumor diagnosis, in order to provide a comprehensive description of these symptoms as well as their potential relationship with delay in the diagnosis. A systematic literature review on case reports of brain tumors and psychiatric symptoms from 1970 to 2020 was conducted on PubMed, Ovid, Psych Info, and MEDLINE. Exclusion criteria comprised tumors not included in the World Health Organization (WHO) Classification 4th edition and cases in which psychiatric symptoms were absent or followed the diagnosis. A total of 165 case reports were analyzed. In a subset of patients with brain tumors, psychiatric symptoms can be the only manifestation or precede focal neurological signs by months or even years. The appearance of focal or generalized neurological symptoms after, rather than along with, psychiatric symptoms was associated with a significant delay in the diagnosis in adults. A timely assessment of psychiatric symptoms might help to improve early diagnosis of brain tumors

The synthetic peptide P111-136 derived from the C-terminal domain of heparin affin regulatory peptide inhibits tumour growth of prostate cancer PC-3 cells

<p>Abstract</p> <p>Background</p> <p>Heparin affin regulatory peptide (HARP), also called pleiotrophin, is a heparin-binding, secreted factor that is overexpressed in several tumours and associated to tumour growth, angiogenesis and metastasis. The C-terminus part of HARP composed of amino acids 111 to 136 is particularly involved in its biological activities and we previously established that a synthetic peptide composed of the same amino acids (P111-136) was capable of inhibiting the biological activities of HARP. Here we evaluate the ability of P111-136 to inhibit <it>in vitro </it>and <it>in vivo </it>the growth of a human tumour cell line PC-3 which possess an HARP autocrine loop.</p> <p>Methods</p> <p>A total lysate of PC-3 cells was incubated with biotinylated P111-136 and pulled down for the presence of the HARP receptors in Western blot. <it>In vitro</it>, the P111-136 effect on HARP autocrine loop in PC-3 cells was determined by colony formation in soft agar. <it>In vivo</it>, PC-3 cells were inoculated in the flank of athymic nude mice. Animals were treated with P111-136 (5 mg/kg/day) for 25 days. Tumour volume was evaluated during the treatment. After the animal sacrifice, the tumour apoptosis and associated angiogenesis were evaluated by immunohistochemistry. <it>In vivo </it>anti-angiogenic effect was confirmed using a mouse Matrigel™ plug assay.</p> <p>Results</p> <p>Using pull down experiments, we identified the HARP receptors RPTPβ/ζ, ALK and nucleolin as P111-136 binding proteins. <it>In vitro</it>, P111-136 inhibits dose-dependently PC-3 cell colony formation. Treatment with P111-136 inhibits significantly the PC-3 tumour growth in the xenograft model as well as tumour angiogenesis. The angiostatic effect of P111-136 on HARP was also confirmed using an <it>in vivo </it>Matrigel™ plug assay in mice</p> <p>Conclusions</p> <p>Our results demonstrate that P111-136 strongly inhibits the mitogenic effect of HARP on <it>in vitro </it>and <it>in vivo </it>growth of PC-3 cells. This inhibition could be linked to a direct or indirect binding of this peptide to the HARP receptors (ALK, RPTPβ/ζ, nucleolin). <it>In vivo</it>, the P111-136 treatment significantly inhibits both the PC-3 tumour growth and the associated angiogenesis. Thus, P111-136 may be considered as an interesting pharmacological tool to interfere with tumour growth that has now to be evaluated in other cancer types.</p

Coumarins derivatives and inflammation: Review of their effects on the inflammatory signaling pathways

International audienceNatural and synthetic coumarins have been extensively described in the literature as effective drugs with several pharmacological activities. Many valuable publications have shown the anti-inflammatory potential of these compounds suggesting that coumarins could be an interesting scaffold for developing new therapeutic anti-inflammatory agents. However, despite the continuous efforts of research in this field, no major breakthrough was yet achieved and only a few coumarin-like drugs are commercially available.In the present article, we reviewed the most relevant studies conducted in the last two decades (2000–2021) and presenting evidence for the anti-inflammatory mechanisms of coumarins. The review provides a comprehensive survey of scientific research revealing through multiple in vitro and in vivo models the effect of natural and synthetic coumarins on components of the Toll-like receptors (TLR), Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT), Inflammasomes, mitogen-activated protein kinase (MAPK), nuclear factor- κ-light-chain-enhancer of activated B cells (NF- κB) and transforming growth factor-β/small mothers against decapentaplegic (TGF-β/SMAD) pathways

IMPACT OF DIC TREATMENT ON THE ANTIOXIDANT PROFILE OF RHEUM RIBES L. RHIZOME EXTRACTS

Rheum ribes L. (rhubarb), which belongs to the family of Polygonaceae, is one of the most important medicinal Mediterranean plants. Its aqueous decoctions have become a common practice among patients suffering from diabetes, hypertension, obesity, and diarrhea. Therefore, it is worth using techniques capable of increasing the extraction of valuable compounds while providing effective microbiological decontamination of the raw material. Instant Controlled Pressure-Drop (DIC) is a high temperature-short time treatment (HTST) followed by an abrupt pressure-drop (ΔP/Δt>500 kPa s-1) towards a vacuum (about 5 kPa). It allows a controlled expansion to ensure better diffusivity and higher availability of the active molecules. Indeed, DIC treatment has already shown its potential in improving the conventional extraction of active molecules and essential oils from plants. Rheum ribes L. rhizomes were collected from Chouf, Lebanon, dried from 1.33±0.28 to 0.16±0.02 g H2O/g dry-basis, ground, and sieved into small particles of 0.4-2 mm. DIC treatment was used with a saturated steam pressure ranged from 200 to 600 kPa for 10 to 40 s. The antiradical characteristics (DPPH· test) of aqueous extracts of DIC-treated samples were determined. At low levels of saturated steam-pressure, DIC treatment showed a significant impact on the scavenging capacity of the rhizomes. Thus, at 260 kPa, it recorded the lowest IC50 value (54.56±0.19 μg/mL) versus 71.29±0.499 μg/mL for the untreated rhizomes (RM for raw material) used as a control. DIC processing parameters will be optimized in our future work to obtain the highest yield of phytochemicals while assessing the antimicrobial, cytotoxic, and bioactive properties of the aqueous extracts of R. ribes L. rhizomes