In Planta Colonization and Role of T6SS in Two Rice Kosakonia Endophytes.

Endophytes live inside plants and are often beneficial. Kosakonia is a novel bacterial genus that includes many diazotrophic plant-associated isolates. Plant–bacteria studies on two rice endophytic Kosakonia beneficial strains were performed, including comparative genomics, secretome profiling, in planta tests, and a field release trial. The strains are efficient rhizoplane and root endosphere colonizers and localized in the root cortex. Secretomics revealed 144 putative secreted proteins, including type VI secretory system (T6SS) proteins. A Kosakonia T6SS genomic knock-out mutant showed a significant decrease in rhizoplane and endosphere colonization ability. A field trial using rice seed inoculated with Kosakonia spp. showed no effect on plant growth promotion upon nitrogen stress and microbiome studies revealed that Kosakonia spp. were significantly more present in the inoculated rice. Comparative genomics indicated that several protein domains were enriched in plant-associated Kosakonia spp. This study highlights that Kosakonia is an important, recently classified genus involved in plant–bacteria interaction

Câncer de fígado: ameaça nova ou antiga para os jovens dos países em desenvolvimento?

Among the most frequent malignancies worldwide, hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death (1). Its incidence has doubled over the past two decades, with the greatest burden occurring in low- and middle-income countries. Malignant primary liver tumors are usually described as a pathology affecting mainly men older than 40 years with a cirrhotic liver; they have rarely been reported in younger people and usually, in those younger than 40, most commonly hepatoblastoma.Entre las neoplasias malignas más frecuentes del mundo, el carcinoma hepatocelular (CHC) es la segunda causa de muerte relacionada con el cáncer (1). Su incidencia se ha duplicado durante las dos últimas décadas y la mayor carga se produce en los países de ingresos bajos y medianos. Los tumores hepáticos primarios malignos suelen describirse como una patología que afecta principalmente a hombres mayores de 40 años con un hígado cirrótico; rara vez se han registrado en personas más jóvenes y normalmente, en menores de 40, lo más común es el hepatoblastoma.Entre as doenças malignas mais comuns no mundo inteiro, o carcinoma hepatocelular (HCC) é a segunda principal causa de morte relacionada ao câncer (1). Sua incidência dobrou nas últimas duas décadas, sendo que a maior carga ocorreu em países de baixa e média renda. Os tumores primários malignos do fígado são geralmente descritos como uma patologia que afeta principalmente homens acima de 40 anos de idade com fígado cirrótico; raramente foram relatados em pessoas mais jovens e geralmente, naqueles com menos de 40 anos, o mais comum é o hepatoblastoma

Marine Actinomycetes: A New Source of Compounds against the Human Malaria Parasite

Background Malaria continues to be a devastating parasitic disease that causes the death of 2 million individuals annually. The increase in multi-drug resistance together with the absence of an efficient vaccine hastens the need for speedy and comprehensive antimalarial drug discovery and development. Throughout history, traditional herbal remedies or natural products have been a reliable source of antimalarial agents, e.g. quinine and artemisinin. Today, one emerging source of small molecule drug leads is the world's oceans. Included among the source of marine natural products are marine microorganisms such as the recently described actinomycete. Members of the genus Salinispora have yielded a wealth of new secondary metabolites including salinosporamide A, a molecule currently advancing through clinical trials as an anticancer agent. Because of the biological activity of metabolites being isolated from marine microorganisms, our group became interested in exploring the potential efficacy of these compounds against the malaria parasite.[br/] Methods We screened 80 bacterial crude extracts for their activity against malaria growth. We established that the pure compound, salinosporamide A, produced by the marine actinomycete, Salinispora tropica, shows strong inhibitory activity against the erythrocytic stages of the parasite cycle. Biochemical experiments support the likely inhibition of the parasite 20S proteasome. Crystal structure modeling of salinosporamide A and the parasite catalytic 20S subunit further confirm this hypothesis. Ultimately we showed that salinosporamide A protected mice against deadly malaria infection when administered at an extremely low dosage.[br/] Conclusion These findings underline the potential of secondary metabolites, derived from marine microorganisms, to inhibit Plasmodium growth. More specifically, we highlight the effect of proteasome inhibitors such as salinosporamide A on in vitro and in vivo parasite development. Salinosporamide A (NPI-0052) now being advanced to phase I trials for the treatment of refractory multiple myeloma will need to be further explored to evaluate the safety profile for its use against malaria

Excess mortality in patients with cancer during the COVID-19 pandemic in Peru: an analysis of death registry data

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La simalikalactone E, molécule antipaludique et anticancer = Simalikalactone E, anti-malarial and anticancer molecule

En octobre dernier, le Prix 2013 de l’innovation pour le Sud décerné par l’Institut de recherche pour le développement (IRD) récompensait la découverte d’une molécule aux propriétés miraculeuses : la simalikalactone E. Isolé de Quassia amara, une plante médicinale amazonienne, cette molécule est à la fois un antipaludique et un anticancer. Cette découverte permettra-t-elle à la plante d’accéder au statut des grandes plantes médicaments qui ont bouleversé la thérapeutique en sauvant des milliers de vies ? C’est l’espoir nourri par les chercheurs. Histoire d’une découverte

New findings on Simalikalactone D, an antimalarial compound from Quassia amara L. (Simaroubaceae)

Quassia amara L (Simaroubaceae) is a species widely used as tonic and is claimed to be an efficient antimalarial all over the Northern part of the Amazon basin. Quassinoid compound Simalikalactone D (SkD) has been shown to be one of the molecules responsible for the antiplasmodial activity of a watery preparation made out of juvenile fresh leaves of this plant. Because of its strong antimalarial activity, we decided to have a further insight of SkD pharmacological properties, alone or in association with classical antimalarials. At concentrations of up to 200 mu M, we showed herein that SkD did not exert any apoptotic or necrotic activities in vitro on lymphoblastic cells. However, an antiproliferative effect was evident at concentrations higher than 45 nM. SkD was inefficient at inhibiting heme biomineralization and the new permeability pathways induced by the parasite in the host erythrocyte membrane. With respect to Plasmodium falciparum erythrocytic stages, SkD was almost inactive on earlier and later parasite stages, but potently active at the 30th h of parasite cycle when DNA replicates in mature trophozoites. In vitro combination studies with conventional antimalarial drugs showed that SkD synergizes with atovaquone (ATO). The activity of ATO on the Plasmodium mitochondrial membrane potential was enhanced by SkD, which on its own had a poor effect on this cellular parameter

Modern teaching of military surgery: why and how to prepare the orthopaedic surgeons before deployment? The French experience

Improved survival of combat casualties in modern conflicts is especially due to early access to damage control resuscitation and surgery in forward surgical facilities. In the French Army, these small mobile units are staffed with one general surgeon and one orthopaedic surgeon who must be able to perform any kind of trauma or non trauma emergency surgery. METHODS: This concept of forward surgery requires a solid foundation in general surgery which is no longer provided by the current surgical programs due to an early specialization of the residents. Obviously a specific training is needed in war trauma due to the special pathology and practice, but also in humanitarian care which is often provided in military field facilities. RESULTS: To meet that demand the French Military Health Service Academy created an Advanced Course for Deployment Surgery (ACDS), also called CACHIRMEX (Cours Avancé de CHIRurgie en Mission EXtérieure). Since 2007 this course is mandatory for young military surgeons before their first deployment. Orthopaedic trainees are particularly interested in learning war damage control orthopaedic tactics, general surgery life-saving procedures and humanitarian orthopaedic surgery principles in austere environments. CONCLUSION: Additional pre-deployment training was recently developed to improve the preparation of mobile surgical teams, as well as a continuing medical education for any active-duty or reserve surgeon to be deployed

An atypical age-specific pattern of hepatocellular carcinoma in Peru: a threat for Andean populations.

In South America, the highest incidence of primary liver cancer is observed in Peru. However, national estimations on hepatocellular carcinoma incidence and mortality are approximated using aggregated data from surrounding countries. Thus, there is a lack of tangible information from Peru that impairs an accurate description of the local incidence, presentation, and outcomes of hepatocellular carcinoma. The present study attempts to fill this gap and assesses the clinical epidemiology of hepatocellular carcinoma in this country.A retrospective cohort study was conducted by analysing the medical charts of 1,541 patients with hepatocellular carcinoma admitted between 1997 and 2010 at the Peruvian national institute for cancer. The medical records including liver function, serologic status, and tumor pathology and stage were monitored. Statistical analyses were performed in order to characterize tumor presentation according to demographic features, risk factors, and regional origin.Surprisingly, the age distribution of the patient population displayed bimodality corresponding to two distinct age-based subpopulations. While an older group was in keeping with the age range observed for hepatocellular carcinoma around the world, a younger population displayed an abnormally juvenile mean age of 25.5 years old. In addition, each subpopulation displayed age-specific pathophysiological and clinical characteristics.The analysis suggests two different age-specific natural histories of hepatocellular carcinoma in the Peruvian patient population. This otherwise unusual tumor process that is ongoing in younger patients leads to the hypothesis that there may be a Peru-endemic risk factor driving hepatocarcinogenesis in the local population

Negative serology of Fasciola hepatica infection in patients with liver cancer in Peru: a preliminary report

Abstract INTRODUCTION: The etiology of several hepatocellular carcinoma (HCC) cases remains largely unknown. Although Fasciola hepatica has been associated with liver fibrosis in Latin America, it has not yet been associated with HCC. This study aimed to determine the existence of specific IgG antibodies against F. hepatica in the serum samples of HCC patients. METHODS In total, 13 serum samples from 13 HCC patients were screened using Fas2-ELISA. RESULTS Fas2-ELISA demonstrated negative results in all HCC patients included in this study. CONCLUSIONS The pre-existence of F. hepatica infection in HCC patients needs to be further investigated in epidemiological and experimental studies

On the risk of further excluding outcast patient populations in South America

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