Cratoxylum formosum ssp. pruniflorum activates the TRAIL death receptor complex and inhibits topoisomerase I

Abstract Six species of Cratoxylum are found in Thailand. Whether the Cratoxylum formosum ssp. pruniflorum (CFP) has anticancer properties requires investigation. CFP exhibited cytotoxicity against hepatocellular carcinoma HepG2 cells. Based on FTIR microspectroscopy, CFP raised the respective lipid and nucleic acid content and β-pleated sheet in HepG2 cells, suggesting a change in the secondary protein structure. CFP induced apoptosis by increasing the activities of various caspases. Overexpression of TRAILR2 indicated the extrinsic pathway while expression of Bax/Bcl-2 ratio indicated the intrinsic pathway and decreased expression of Bid indicated cross-talk between the two. CFP alkylated the DNA and caused DNA damage, which may be the initial step in the intrinsic pathway. CFP indirectly and directly inhibited Top IB enzyme activity and decreased PARP—the protein-related DNA repair process. CFP could, thus, protect the resistance mechanism of cancer by reversing the effect of Top as confirmed by apoptosis induction in the resistant HepG2 cells. The phytochemical analysis suggested that the compounds playing an important role in the anticancer activity of CFP are a group of xanthones

An Unusual Case of Adrenal Metastasis from Colorectal Cancer: Computed Tomography and Fluorine 18-Fluoro-Deoxy-Glucose Positron Emission Tomography-Computed Tomography Features and Literature Review

Incidentally discovered adrenal masses are a common diagnostic problem. While computed tomography (CT) and magnetic resonance (MR) imaging can adequately characterize most benign or malignant adrenal masses, in some cases the results are indeterminate. We report and discuss a case of an adrenal metastasis with misleading clinical and CT features, in which an abnormal metabolic uptake detected through fluorine 18-fluoro-deoxy-glucose positron emission tomography (18F-FDG PET)-CT raised the suspicion of adrenal metastasis relatively early compared with apparently normal results on repeated follow-up CT examinations

Cholesterol depletion inhibits synaptic transmission and synaptic plasticity in rat hippocampus.

Several neurodegenerative disorders are associated with impaired cholesterol homeostasis in the nervous system where cholesterol is known to play a role in modulating synaptic activity and stabilizing membrane microdomains. In the present report, we investigated the effects of methyl-beta-cyclodextrin-induced cholesterol depletion on synaptic transmission and on the expression of 1) paired-pulse facilitation (PPF); 2) paired-pulse inhibition (PPI) and 3) long-term potentiation (LTP) in the CA1 hippocampal region. Results demonstrated that cyclodextrin strongly reduced synaptic transmission and blocked the expression of LTP, but did not affect PPF and PPI. The role of glutamatergic and GABAergic receptors in these cholesterol depletion-mediated effects was evaluated pharmacologically. Data indicate that, in cholesterol depleted neurons, modulation of synaptic transmission and synaptic plasticity phenomena are sustained by AMPA-, kainate-and NMDA-receptors but not by GABA-receptors. The involvement of AMPA-and kainate-receptors was confirmed by fluorimetric analysis of intracellular calcium concentrations in hippocampal cell cultures. These data suggest that modulation of receptor activity by manipulation of membrane lipids is a possible therapeutic strategy in neurodegenerative disease

Impact of Cold Somatostatin Analog Administration on Somatostatin Receptor Imaging: A Systematic Review

Purpose The interactions between the administration of cold somatostatin analogs (cSAs) and their radiolabeled counterpart remain unclear, and discontinuation before imaging is still advised as a precaution. The aim of this systematic review is to evaluate the consequences of cSA administration on tumoral and surrounding healthy organs' uptake at somatostatin receptor (SSTR) imaging with SPECT or PET. Methods After registration of the study on Prospero (CRD42022360260), an electronic search of PubMed and Scopus databases was performed. Inclusion criteria were as follows: human patients referred for SSTR imaging for oncological purposes; at least 1 examination performed either before cSA administration or after a long-enough withdrawal of cSA treatment; at least 1 examination was performed under cSA treatment. Included articles were independently appraised by 2 authors using the standardized protocol provided by the Quality Assessment of Diagnostic Accuracy Studies. Discrepancies were solved by consensus. Results A total of 12 articles were included, 4 using 111In-pentetreotide and 8 using 68Ga-DOTA peptides. Administration of cSAs consistently resulted in decreased spleen and liver uptake (6.9% to 80% for spleen, 10% to 60% for liver) and increased tumor-to-background or tumor-to-healthy organ ratios. After cSA treatment, tumor uptake alone was unchanged or moderately decreased. Similar results were noted whether patient was octreotide-naive. Conclusion Impairment in SSTR imaging quality after cSA administration has not been demonstrated. On the contrary, the administration of cSAs seems to improve the contrast between tumoral lesions and the surroundings

Miglustat Reverts the Impairment of Synaptic Plasticity in a Mouse Model of NPC Disease

Niemann-Pick type C disease is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol within the late endolysosomal compartment of cells and accumulation of gangliosides and other sphingolipids. Progressive neurological deterioration and insurgence of symptoms like ataxia, seizure, and cognitive decline until severe dementia are pathognomonic features of the disease. Here, we studied synaptic plasticity phenomena and evaluated ERKs activation in the hippocampus of BALB/c NPC1-/- mice, a well described animal model of the disease. Our results demonstrated an impairment of both induction and maintenance of long term synaptic potentiation in NPC1-/- mouse slices, associated with the lack of ERKs phosphorylation. We then investigated the effects of Miglustat, a recent approved drug for the treatment of NPCD. We found that in vivo Miglustat administration in NPC1-/- mice was able to rescue synaptic plasticity deficits, to restore ERKs activation and to counteract hyperexcitability. Overall, these data indicate that Miglustat may be effective for treating the neurological deficits associated with NPCD, such as seizures and dementia

Sintomas visuais de deficiências nutricionais em grama-do-cerrado (Mesosetum chaseae).

Em experimento de casa de vegetação, cultivou-se Mesosetum chaseae Luces (grama-do-cerrado) em soluçãonutritiva, tendo como tratamentos a solução completa, as omissões individuais dos macronutrientes N, P, K, Ca, Mg, S e micronutrientes B, Zn, Fe e Mn. Fez-se o acompanhamento semanal da manifestação dos sintomas visuais de deficiência após o transplantio, além de medições biométricas tais como altura máxima, número de perfilhos e produção da matéria seca da parte aérea (MSPA) e da raiz (MSR) da grama-do-cerrado. A forrageira grama-do-cerrado mostrou-se mais exigente em N, P e Fe demonstrando sintomas de deficiência na fase inicial de crescimento. Para os índices biométricos e de produção analisados, todos apresentaram diferenças significativas entre os tratamentos. O Ca e o Mg foram os nutrientes menos limitantes para o crescimento e desenvolvimento da grama-do-cerrado.bitstream/item/157942/1/BP110.pd

Relative expression of TAp73 and ΔNp73 isoforms

The transcription factor p73 belongs to the p53 family of tumour suppressors and similar to other family members, transcribed as different isoforms with opposing pro- and anti-apoptotic functions. Unlike p53, p73 mutations are extremely rare in cancers. Instead, the pro-apoptotic activities of transcriptionally active p73 isoforms are commonly inhibited by over-expression of the dominant negative p73 isoforms. Therefore the relative ratio of different p73 isoforms is critical for the cellular response to a chemotherapeutic agent. Here, we analysed the expression of N-terminal p73 isoforms in cell lines and mouse tissues. Our data showed that the transcriptionally competent TAp73 isoform is abundantly expressed in cancer cell lines compared to the dominant negative ΔNp73 isoform. Interestingly, we detected higher levels of ΔNp73 in some mouse tissues, suggesting that ΔNp73 may have a physiological role in these tissues

Tecidos vegetais.

Amostragem; Procedimento para coleta de amostras de folhas no campo; Coleta da amostra; Identificacao da amostra; Moagem; Armazenagem; Integridade da amostra; Problemas de contaminacao; Arquivo de amostra

Circulating tumor DNA in patients with colorectal adenomas: assessment of detectability and genetic heterogeneity.

Improving early detection of colorectal cancer (CRC) is a key public health priority as adenomas and stage I cancer can be treated with minimally invasive procedures. Population screening strategies based on detection of occult blood in the feces have contributed to enhance detection rates of localized disease, but new approaches based on genetic analyses able to increase specificity and sensitivity could provide additional advantages compared to current screening methodologies. Recently, circulating cell-free DNA (cfDNA) has received much attention as a cancer biomarker for its ability to monitor the progression of advanced disease, predict tumor recurrence and reflect the complex genetic heterogeneity of cancers. Here, we tested whether analysis of cfDNA is a viable tool to enhance detection of colon adenomas. To address this, we assessed a cohort of patients with adenomas and healthy controls using droplet digital PCR (ddPCR) and mutation-specific assays targeted to trunk mutations. Additionally, we performed multiregional, targeted next-generation sequencing (NGS) of adenomas and unmasked extensive heterogeneity, affecting known drivers such as APC, KRAS and mismatch repair (MMR) genes. However, tumor-related mutations were undetectable in patients' plasma. Finally, we employed a preclinical mouse model of Apc-driven intestinal adenomas and confirmed the inability to identify tumor-related alterations via cfDNA, despite the enhanced disease burden displayed by this experimental cancer model. Therefore, we conclude that benign colon lesions display extensive genetic heterogeneity, that they are not prone to release DNA into the circulation and are unlikely to be reliably detected with liquid biopsies, at least with the current technologies

BRAF^V600E-mutated serrated colorectal neoplasia drives transcriptional activation of cholesterol metabolism

Abstract BRAF mutations occur early in serrated colorectal cancers, but their long-term influence on tissue homeostasis is poorly characterized. We investigated the impact of short-term (3 days) and long-term (6 months) expression of Braf V600E in the intestinal tissue of an inducible mouse model. We show that Braf V600E perturbs the homeostasis of intestinal epithelial cells, with impaired differentiation of enterocytes emerging after prolonged expression of the oncogene. Moreover, Braf V600E leads to a persistent transcriptional reprogramming with enrichment of numerous gene signatures indicative of proliferation and tumorigenesis, and signatures suggestive of metabolic rewiring. We focused on the top-ranking cholesterol biosynthesis signature and confirmed its increased expression in human serrated lesions. Functionally, the cholesterol lowering drug atorvastatin prevents the establishment of intestinal crypt hyperplasia in Braf V600E -mutant mice. Overall, our work unveils the long-term impact of Braf V600E expression in intestinal tissue and suggests that colorectal cancers with mutations in BRAF might be prevented by statins