Notes

Polyether ionophore kijimicin inhibits growth of Toxoplasma gondii and settings serious toxoplasmosis in rats.
Bartonella bacilliformis a gram-negative facultative aerobe responsible for the Carrion's disease widely distributed in Ecuador, Peru, and Colombia with a high mortality rate when no specific treatment is received. B bacilliformis is transmitted by Sand fly (Lutzomyia verrucarum) to healthy individuals. Immunoinformatic and subtractive proteomics approaches were employed in this study to prioritize the best candidates for vaccine designing. These approaches resulted in five vaccine candidates, flagellar biosynthetic protein (Uniprot ID A1UTU1), heme exporter protein C (UniProt ID A1UU82), Cytochrome c-type biogenesis protein (Uniprot ID A1URZ7), Hemin ABC transporter (Uniprot ID A1US20) and Phosphatidate cytidylyltransferase (Uniprot ID A1USE3). The mentioned proteins are antigenic and essential for pathogen survival. A range of immune-informatics tools was applied for the prediction of B and T cell epitopes for the vaccine candidate proteins. In-silico vaccine was constructed using carefully evaluated epitopes and consequently modeled for docking with human Toll-like receptor 4. TLR-4 agonist 50S ribosomal protein L7/L12 (UniproKB ID; P9WHE3) was linked to the vaccine as an adjuvant to boost immune response towards the vaccine. For stability evaluation of the vaccine-TLR-4 docked complex, MD simulations were performed. The final vaccine was back-translated and cloned in Eschericia coli to attain the maximal expression of the vaccine protein. The maximal expression was ensured, and the CAI score of 0.96 was reported. The current vaccine requires future experimental validation to confirm its effectiveness. The vaccine developed will be helpful to protect against B bacilliformis associated infections.Acute gastroenteritis (AG) is responsible for 525,000 deaths worldwide in children under-5-years and is caused by the Human Cosavirus (HCoSV; family Picornaviridae, Genus Cosavirus). Although its health importance, a significant percentage of diarrhea cases (≈ 40 %) still of unknown etiology. In Brazil, few studies have reported HCoSV-A sequences analyzing partial 5' UTR. This study characterized the first near-complete genome of a Cosavirus A (strain AM326) from a child hospitalized with AG in Amazonas state, Northern Brazil. High throughput sequencing (HTS) was performed using the HiSeq™ 2500 platform (Illumina) in one fecal specimen collected from the Surveillance of Rotavirus Network of the Evandro Chagas Institute collected in 2017. Sequence reads were assembled by the De Novo approach using three distinct algorithmic (IDBA-UD, Spades, and MegaHit). The final contig was recovered from the HCoSV-AM326 sample revealing 7,735 nt in length (SRA number SRR12535029; GenBank MT023104) and the genetic characterization, as well as phylogenetic analysis demonstrated a new variant strain from Brazil, highlighting the association of HCoSV-A as a possible causative agent of AG. This finding demonstrates the importance of the metagenomic approach to elucidate cases of diarrhea without a defined etiology, as well as providing a better understanding about the virus genetics, evolution and epidemiology.Selective estrogen receptor modulators (SERMs) are a class of compounds that bind to estrogen receptors (ERs) and possess estrogen agonist or antagonist actions in different tissues. As such, they are widely used drugs. For instance, tamoxifen, the most prescribed SERM, is used to treat ERα-positive breast cancer. Aside from their therapeutic targets, SERMs have the capacity to broadly affect cellular cholesterol metabolism and handling, mainly through ER-independent mechanisms. Cholesterol metabolism reprogramming is crucial to meet the needs of cancer cells, and different key processes involved in cholesterol homeostasis have been associated with cancer progression. Therefore, the effects of SERMs on cholesterol homeostasis may be relevant to carcinogenesis, either by contributing to the anticancer efficacy of these compounds or, conversely, by promoting resistance to treatment. Understanding these aspects of SERMs actions could help to design more efficacious therapies. Herein we review the effects of SERMs on cellular cholesterol metabolism and handling and discuss their potential in anticancer pharmacology.Hepatocellular carcinoma(HCC) is one of the most common forms of cancer, and accounts for a high proportion of cancer-associated deaths. Growing evidences have demonstrated that non- protein-coding regions of the genome could give rise to transcripts, termed noncoding RNA (ncRNA), that form novel functional layers of the cellular activity. ncRNAs are implicated in different molecular mechanisms and functions at transcriptional, translational and post-translational levels. An increasing number of studies have demonstrated a complex array of molecular and cellular functions of ncRNAs in different stages of the HCC tumorigenesis, either in an oncogenic or tumor-suppressive manner. As a result, several pre-clinical studies have highlighted the great potentials of ncRNAs as novel biomarkers for cancer diagnosis or therapeutics in targeting HCC progression. In this review, we briefly described the characteristics of several representative ncRNAs and summarized the latest findings of their roles and mechanisms in the development of HCC, in order to better understand the cancer biology and their potential clinical applications in this malignancy.Platinum resistant ovarian cancer, usually defined as progression occurring within 6 months after completing platinum-based therapy, is a heterogeneous disease with poor prognosis and short survival (less than 18 months). Pirtobrutinib It is typically considered as a "cold tumor", characterized by reduced infiltration by immune cells, particularly CD8+ T cells. Response rate to anti-PD1/PD-L1 monotherapy is low, not exceeding 8%. Multiple therapeutic strategies are currently investigated in order to increase response rates to anti-PD1/PD-L1 through adding chemotherapy, anti-angiogenic agents, DNA damage (PARP inhibitors, cyclophosphamide and/or radiotherapy) or other immune checkpoint inhibitors (CTLA-4, etc.). Ovarian clear cell carcinoma, a rare histotype characterized by primary platinum-resistance, recently showed anecdotal but promising response rates to immune checkpoint blockade. Other immunotherapeutic approaches such as adoptive T cell therapy, vaccines and targeting myeloid immune checkpoints like "don't eat me" signal CD47 are currently investigated.
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