Methods and compositions for treating atheroma, tumors and other neoplastic tissue

Injectible formulations comprising motexafin gadolinium are described herein.Board of Regents, University of Texas Syste

Method and compositions for treating atheroma, tumors and other neoplastic tissue

The radiation sensitization potential of a candidate compound can be screened by determine its ability to generate one or more reactive oxygen species under appropriate conditions. Compounds determined to have radiation sensitization potential are employed in methods for treating atheroma, tumors and other neoplastic tissue as well as other conditions that typically responsive to radiation sensitization.Board of Regents, University of Texas Syste

Phosphoramidite derivatives of macrocycles

The invention is directed to phosphoramidite derivatives of macrocycles, such as porphyrins and expanded porphyrins, including sapphyrins and texaphyrins. The phosphoramidite derivatives are useful as intermediates in the preparation of macrocycle-oligonucleotide conjugates.Board of Regents, University of Texas Syste

Method of phosphate ester hydrolysis

A method of phosphate ester hydrolysis including incubating a solution of an aqueous phosphate ester with a metallotexaphyrin complex under conditions and for a time sufficient to hydrolyze the phosphate ester. The metal is a metal cation having catalytic activity for ester bond hydrolysis in aqueous solution. Phosphate ester substrates include nucleic acid such as RNA, phosphoric anhydrides, phospholipids, and alkyl phosphate esters.Board of Regents, University of Texas Syste

Phosphoramidite derivatives of texaphyrins

The invention is directed to a method of incorporating expanded porphyrins, and particularly of incorporating a sapphyrin or a texaphyrin, before, during, or after chemical synthesis of an oligomer to form an expanded porphyrin-oligonucleotide conjugate, and particularly a sapphyrin- or texaphyrin-oligonucleotide conjugate. This method includes reacting derivatized nucleotides and a sapphyrin or a texaphyrin in a desired order in an automated or manual DNA synthesizer having a solid support to form a sapphyrin- or a texaphyrin-oligonucleotide conjugate.Board of Regents, University of Texas Syste

Method of magnetic resonance image enhancement

Texaphyrins are provided for use as radiation sensitizers. Advantageous properties of texaphyrins for use as a radiation sensitizer include: i) a low redox potential which allows radiation-induced hydrated electrons to flow to texaphyrin rather than neutralizing hydroxyl radicals, allowing hydroxyl radicals to cause cellular damage, ii) a relatively stable texaphyrin radical that reacts readily to covalently modify neighboring molecules causing further cellular damage, iii) intrinsic biolocalization, and iv) indifference to the presence or absence of O.sub.2. These properties allow texaphyrins to be particularly effective for treating the hypoxic areas of solid neoplasms. Methods of treatment for an individual having a neoplasm or atheroma include the use of a texaphyrin as a radiation sensitizer and as an agent for photodynamic tumor therapy, or the use of a texaphyrin for internal and for external ionizing radiation. Novel texaphyrins are provided.Board of Regents, University of Texas Syste

Texaphyrin solid supports and devices

The present invention provides various novel matrix-supported texaphyrins in which a polymeric or solid matrix is covalently modified by the addition of one or more texaphyrins or texaphyrin derivatives. Described are methods of making various polymer-supported texaphyrins, including texaphyrin chromatographic supports, and devices such as catheters, as may be used, for example, in the separation of neutral and anionic species and in applications concerning phosphate ester hydrolysis, other catalytic schemes, MRI, and PDT.Board of Regents, University of Texas Syste

Human cases of simultaneous echinococcosis and tuberculosis - significance and extent in China

During analysis of retrospective community survey data, we identified two patients from Xiji County, south Ningxia Hui Autonomous Region with simultaneous echinococcosis and tuberculosis (TB), representing the first such reports for China. As the echinococcosis chronicity increased, the immune profile in both subjects changed from a Th1 to Th2 response, as shown by a TB skin test, originally positive, becoming negative. Such an elevated Th2 immune profile, with subsequent suppression of the Th1 immune response, is a common feature of chronic helminth infections. Given the difficulties in definitive diagnosis, and the potential increased susceptibility for TB infection in patients with advanced echinococcosis, we suggest that combined TB/echinococcosis surveys be undertaken in this area in the future. This would allow early diagnosis of both TB and echinococcosis cases with better prognosis for effective and sustainable treatment outcomes, ultimately reducing associated morbidity and mortality, and also the overall financial costs to the individual and the public health care system in this under developed part of China

mtDNA depletion confers specific gene expression profiles in human cells grown in culture and in xenograft

<p>Abstract</p> <p>Background</p> <p>Interactions between the gene products encoded by the mitochondrial and nuclear genomes play critical roles in eukaryotic cellular function. However, the effects mitochondrial DNA (mtDNA) levels have on the nuclear transcriptome have not been defined under physiological conditions. In order to address this issue, we characterized the gene expression profiles of A549 lung cancer cells and their mtDNA-depleted ρ⁰counterparts grown in culture and as tumor xenografts in immune-deficient mice.</p> <p>Results</p> <p>Cultured A549 ρ⁰cells were respiration-deficient and showed enhanced levels of transcripts relevant to metal homeostasis, initiation of the epithelial-mesenchymal transition, and glucuronidation pathways. Several well-established HIF-regulated transcripts showed increased or decreased abundance relative to the parental cell line. Furthermore, growth in culture versus xenograft has a significantly greater influence on expression profiles, including transcripts involved in mitochondrial structure and both aerobic and anaerobic energy metabolism. However, both <it>in vitro </it>and <it>in vivo</it>, mtDNA levels explained the majority of the variance observed in the expression of transcripts in glucuronidation, tRNA synthetase, and immune surveillance related pathways. mtDNA levels in A549 xenografts also affected the expression of genes, such as <it>AMACR </it>and <it>PHYH</it>, involved in peroxisomal lipid metabolic pathways.</p> <p>Conclusion</p> <p>We have identified mtDNA-dependent gene expression profiles that are shared in cultured cells and in xenografts. These profiles indicate that mtDNA-depleted cells could provide informative model systems for the testing the efficacy of select classes of therapeutics, such as anti-angiogenesis agents. Furthermore, mtDNA-depleted cells grown culture and in xenografts provide a powerful means to investigate possible relationships between mitochondrial activity and gene expression profiles in normal and pathological cells.</p

Genomic, Proteomic and Phenotypic Biomarkers of COVID-19 Severity::Protocol for a Retrospective Observational Study

Background:Background - Health organisations and countries around the world have found it difficult to control the spread of the coronavirus disease 2019. To minimise the impact on the NHS and improve patient care, there is a drive for rapid tests capable of detecting individuals who are at high risk of contracting severe COVID-19. Early work focused on single omic approaches, highlighting a limited amount of information.Objective:Objective - The Covid Response Study (COVRES, NCT05548829) aims to carry out an integrated multi-omic analysis of factors contributing to host susceptibility to SARS-CoV-2 among a patient cohort of 1000 people from the geographically isolated island of Ireland.Methods:Methods - The protocol below describes the study to be carried out in Northern Ireland (NI-COVRES) by Ulster University, the Republic of Ireland component will be described separately. All participants (n=519) were recruited from the Western Health and Social Care Trust, Northern Ireland, forty patients are also being followed up at 1, 3, 6 and 12 months to assess the longitudinal impact of infection on symptoms, general health, and immune response, this is ongoing. Data will be sourced from whole blood, saliva samples, and clinical data from the Northern Ireland Electronic Care Record, general health questionnaire, and the GHQ12 mental health survey. Saliva and blood samples were processed for DNA and RNA prior to whole genomic sequencing, RNA sequencing, DNA methylation, microbiome, 16S, and proteomic analysis. Multi-omics data will be combined with clinical data to produce sensitive and specific prognostic models of severity risk.Results:Results - An initial profile of the cohort has been completed: n=249 hospitalised and n=270 non-hospitalised patients were recruited, 64% were female, the mean age was 45 years. High levels of comorbidity were evident in the hospitalised cohort, with cardiovascular disease and metabolic and respiratory disorders (P&lt;0.001) being the most significant.Conclusions:Conclusion – This study will provide a comprehensive opportunity to study multi-omic mechanisms of COVID-19 severity in re-contactable participants. Clinical Trial: Trial Registration - The trial has been registered as an observational study on clinicaltrials.gov as NCT05548829. An outline of the trial protocol is included; SPIRIT checklist (Supplementary Figure 1)