Phthalocyanines: An Old Dog Can Still Have New (Photo)Tricks!
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ABSTRACT:
SUBMITTER: Schmidt AM
PROVIDER: S-EPMC8126243 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeThe purpose of the study was to: (1) evaluate the subarachnoid space (SAS) width and pial artery pulsation in both hemispheres, and (2) directly compare magnetic resonance imaging (MRI) to near-infrared transillumination/backscattering sounding (NIR-T/BSS) measurements of SAS width changes in healthy volunteers.MethodsThe study was performed on three separate groups of volunteers, consisting in total of 62 subjects (33 women and 29 men) aged from 16 to 39 years. SAS width was assessed by MRI and NIR-T/BSS, and pial artery pulsation by NIR-T/BSS.ResultsIn NIR-T/BSS, the right frontal SAS was 9.1% wider than the left (p<0.01). The SAS was wider in men (p<0.01), while the pial artery pulsation was higher in women (p<0.01). Correlation and regression analysis of SAS width changes between the back- and abdominal-lying positions measured with MRI and NIRT-B/SS demonstrated high interdependence between both methods (r = 0.81, p<0.001).ConclusionsNIR-T/BSS and MRI were comparable and gave equivalent modalities for the SAS width change measurements. The SAS width and pial artery pulsation results obtained with NIR-T/BSS are consistent with the MRI data in the literature related to sexual dimorphism and morphological asymmetries between the hemispheres. NIR-T/BSS is a potentially cheap and easy-to-use method for early screening in patients with brain tumours, increased intracranial pressures and other abnormalities. Further studies in patients with intracranial pathologies are warranted.
| S-EPMC3365109 | biostudies-literature
Project description:Conventional wisdom holds that methylation of RTKs should be restricted to intracellular sites. Alterations--such as deletion, mutation, and proteolytic cleavage events--to the extracellular ligand binding and dimer interface domains of the EGFR can induce EGFR dimer formation, leading to aberrant receptor activation and oncogenic activity. Recently, the extracellular domain of EGFR was also shown to be methylated, suggesting that posttranslational protein methylation events directed to the extracellular dimer interface provide another mechanism to regulate the EGFR activation state by modulating receptor dimerization. Critically, these methylation events abrogate response to conformation-specific therapeutic antibodies such as cetuximab. In this issue of the JCI, Liao et al. investigate the role of protein arginine methyltransferase I (PRMT1) in regulating EGFR function in colorectal cancer. The authors provide evidence that methylation of R198 and R200 within the dimer interface enhances growth factor ligand binding and cetuximab resistance through induction and stabilization of the active EGFR dimer conformation. Delineation of these and other subtleties involved in oncogenic RTK activation and their response to targeted therapies should facilitate the development of improved antibody-based treatments.
| S-EPMC4665791 | biostudies-literature
Project description:Adoptive T cell therapy (ACT) refers to the therapeutic use of T cells. T cells genetically engineered to express chimeric antigen receptors (CAR) constitute the most clinically advanced form of ACT approved to date for the treatment of CD19-positive leukaemias and lymphomas. CARs are synthetic receptors that are able to confer antigen-binding and activating functions on T cells with the aim of therapeutically targeting cancer cells. Several factors are essential for CAR T cell therapy to be effective, such as recruitment, activation, expansion and persistence of bioengineered T cells at the tumour site. Despite the advances made in CAR T cell therapy, however, most tumour entities still escape immune detection and elimination. A number of strategies counteracting these problems will need to be addressed in order to render T cell therapy effective in more situations than currently possible. Non-haematological tumours are also the subject of active investigation, but ACT has so far shown only marginal success rates in these cases. New approaches are needed to enhance the ability of ACT to target solid tumours without increasing toxicity, by improving recognition, infiltration, and persistence within tumours, as well as an enhanced resistance to the suppressive tumour microenvironment.
| S-EPMC6325111 | biostudies-literature
Project description:At one level, obesity is clearly a problem of simple physics, a result of eating too much and not expending enough energy. The more complex question, however, is why do some people eat more than others? Studies of human and mouse genetics over the past two decades have uncovered a number of pathways within the brain that play a key role in the control of food intake. A prime example is the leptin-melanocortin pathway, which we now know greatly contributes to mammalian appetitive behaviour. However, genetic disruption of this pathway remains rare and does not represent the major burden of the disease that is carried by those of us with 'common obesity'. In recent years, genome-wide association studies have revealed more than 100 different candidate genes linked to BMI, with most (including many components of the melanocortin pathway) acting in the central nervous system and influencing food intake. So while severe disruption of the melanocortin pathway results in severe obesity, subtle variations in these genes influence where you might sit in the normal distribution of BMI. As we now enter this 'post-genomics' world, can this new information influence our treatment and management of obese patients?
| S-EPMC6518377 | biostudies-literature
Project description:This Open Question article highlights current advances in the study of non-apoptotic roles of apoptotic proteins. Apoptosis is a highly regulated and energy-requiring process in which cells actively kill themselves. Apoptosis helps remove extra cells to sculpt organs during embryo development and culls damaged cells throughout the body. Apoptosis relies on evolutionarily conserved proteins that include a family of proteases called caspases. Caspases activity has long been considered a hallmark of apoptosis. Yet an emerging body of literature indicates that caspase activity is required for a number of non-lethal processes that range from sculpting cells, removing protein aggregates, changing cell identity during differentiation or de-differentiation, and rebuilding tissues. Failure in each of these processes is associated with human disease. This article is not meant to be an exhaustive review but an introduction to the subject for an educated public, with caspases as a gateway example. I propose that it is time to explore non-apoptotic roles of caspases and other apoptotic proteins, in order to better understand their non-apoptosis function and to leverage new knowledge into new therapies.
| S-EPMC7479936 | biostudies-literature
Project description:The COMBINE method was designed to study congeneric series of compounds including structural information of ligand-protein complexes. Although very successful, the method has not received the same level of attention than other alternatives to study Quantitative Structure Active Relationships (QSAR) mainly because lack of ways to measure the uncertainty of the predictions and the need for large datasets. Active learning, a semi-supervised learning approach that makes use of uncertainty to enhance models' performance while reducing the size of the training sets, has been used in this work to address both problems. We propose two estimators of uncertainty: the pool of regressors and the distance to the training set. The performance of the methods has been evaluated by testing the resulting active learning workflows in 3 diverse datasets: HIV-1 protease inhibitors, Taxol-derivatives and BRD4 inhibitors. The proposed strategies were successful in 80% of the cases for the taxol-derivatives and BRD4 inhibitors, while outperformed random selection in the case of the HIV-1 protease inhibitors time-split. Our results suggest that AL-COMBINE might be an effective way of producing consistently superior QSAR models with a limited number of samples.
| S-EPMC7087723 | biostudies-literature
Project description:Jahchan and colleagues report the use of a biostatistical analysis to identify effective therapeutics for small cell lung cancer (SCLC). Their results reveal a new use for the tricyclic antidepressant imipramine in SCLC and shed light on the therapeutic potential of drug repositioning in cancer and other diseases.
| S-EPMC3878064 | biostudies-literature
Project description:Objective: Human serum albumin (HSA) infusion is a common administration on acute pancreatitis therapy in the Intensive Care Unit (ICU), but its actual association with patients' outcomes has not been confirmed. The study is aimed to determine whether the in-hospital prognosis of ICU patients with acute pancreatitis could benefit from HSA. Methods: 950 acute pancreatitis patients diagnosed in 2008-2019 were extracted from the MIMIC-IV database as our primary study cohort. The primary outcome was in-hospital mortality. We also performed an external validation with a cohort of 104 acute pancreatitis patients after PSM matching from the eICU database. Results: In MIMIC-IV, 228 acute pancreatitis patients received HSA infusion (Alb group) during their hospitalization, while 722 patients did not (non-Alb group). Patients in the Alb group presented a poorer survival curve than the non-Alb group, while this difference disappeared after PSM or IPTW matching (log-rank test: PSM: p = 0.660, IPTW: p = 0.760). After including covariates, no association was found between HSA infusion and patients' in-hospital mortality before and after matching (original cohort: HR: 1.00, 95% CI: 0.66-1.52, p = 0.998). HSA infusion also did not benefit patients' 28-days or ICU mortality, while it was significantly associated with a longer duration of hospital and ICU. In addition, the initial serum albumin levels, infections, the total amount, or the initial timing of infusion did not affect the conclusion. Similarly, in the eICU cohort, HSA infusion was still not a beneficial prognostic factor for patients' in-hospital prognosis (p = 0.087). Conclusion: Intravenous human serum albumin infusion could not benefit acute pancreatitis patients' in-hospital prognosis and was associated with prolonged hospital and ICU duration.
| S-EPMC9198420 | biostudies-literature
Project description:Understanding the mechanism by which streptomycin binds to the small subunit of the mitoribosome may help researchers design less toxic derivatives of this antibiotic.
| S-EPMC9731568 | biostudies-literature
Project description:High throughput screening (HTS) is an important component of lead discovery, with virtual screening playing an increasingly important role. Both methods typically suffer from lack of sensitivity and specificity against their true biological targets. With ever-increasing screening libraries and virtual compound collections, it is now feasible to conduct follow-up experimental testing on only a small fraction of hits. In this context, advances in virtual screening that achieve enrichment of true actives among top-ranked compounds ("early recognition") and, hence, reduce the number of hits to test, are highly desirable. The standard ligand-based virtual screening method for large compound libraries uses a molecular similarity search method that ranks the likelihood of a compound to be active against a drug target by its highest Tanimoto similarity to known active compounds. This approach assumes that the distributions of Tanimoto similarity values to all active compounds are identical (i.e., same mean and standard deviation)-an assumption shown to be invalid (Baldi and Nasr, 2010). Here, we introduce two methods that improve early recognition of actives by exploiting similarity information of all molecules. The first method ranks a compound by its highest z-score instead of its highest Tanimoto similarity, and the second by an aggregated score calculated from its Tanimoto similarity values to all known actives and inactives (or a large number of structurally diverse molecules when information on inactives is unavailable). Our evaluations, which use datasets of over 20 HTS campaigns downloaded from PubChem, indicate that compared to the conventional approach, both methods achieve a ~10% higher Boltzmann-enhanced discrimination of receiver operating characteristic (BEDROC) score-a metric of early recognition. Given the increasing use of virtual screening in early lead discovery, these methods provide straightforward means to enhance early recognition.
| S-EPMC6819673 | biostudies-literature