Intestinal Enterobacteriaceae that Protect Nematodes from the Effects of Benzimidazoles

The objective of this study was to investigate an interaction between nematodes and gut Enterobacteriaceae that use benzimidazoles as a carbon source. By addressing this objective, we identified an anthelmintic resistance-like mechanism for gastrointestinal nematodes. We isolated 30 gut bacteria (family Enterobacteriaceae) that subsist on and putatively catabolize benzimidazole-class anthelmintics. C. elegans was protected from the effects of benzimidazoles when co-incubated with these Enterobacteriaceae that also protect adult ascarids from the effects of albendazole. This bacterial phenotype represents a novel mechanism by which gastrointestinal nematodes are potentially spared from the effects of benzimidazoles, without any apparent fitness cost to the parasite

Mitochondrial Fusion Promotes Steroidogenesis in MA10 Leydig Cells

Infertility affects 1 out of every 6 couples, worldwide, with male infertility playing a primary factor in a third of all cases. Dysregulation of sex hormones is a major cause of infertility. Male hypogonadism is a condition in which the testis does not produce adequate concentrations of testosterone. Males suffering from hypogonadism can be born with the condition or develop it later in life, often from acute injury or infection. Male hypogonadism is treated with testosterone replacement to return testosterone levels to normal. However, one side effect of testosterone treatment is infertility. Understanding mechanisms that regulate the synthesis of sex steroids holds great potential to positively impact reproductive health and overall quality of life. Mitochondria play a key role in the synthesis of all steroid hormones. The first and rate-limiting step in the production of all steroid hormones is the transfer of cholesterol from the outer mitochondrial membrane to the inner membrane. In the current study, we examined the hypothesis that mitochondrial fusion promotes acute steroid synthesis in LH-responsive Leydig cells.https://digitalcommons.unmc.edu/surp2022/1005/thumbnail.jp

Emerging Roles of Urine-Derived Components for the Management of Bladder Cancer: One Man’s Trash is Another Man’s Treasure

Urinary bladder cancer (UBC) is the most common malignancy of the urinary tract in humans, with an estimated global prevalence of 1.1 million cases over 5 years. Due to high rates of recurrence and resistance to chemotherapy, UBC is one of the most expensive cancers to treat, resulting in significant health care costs. There is, therefore, a critical need to develop innovative molecular and cellular tools to refine patient stratification and help predict response to treatment. Urine is an underused resource of biological components shed from bladder tumors, such as exfoliated cells and extracellular vesicles, that could serve as molecular fingerprints and provide valuable biological insights into tumor phenotype and mechanisms of resistance to chemotherapy. Additionally, characterization of urine-derived extracellular vesicles and cells could be used as reliable biomarkers for prediction of response to neoadjuvant therapy

The Edinburgh Addiction Cohort: recruitment and follow-up of a primary care based sample of injection drug users and non drug-injecting controls.

BACKGROUND: Injection drug use is an important public health problem. Epidemiological understanding of this problem is incomplete as longitudinal studies in the general population are difficult to undertake. In particular little is known about early life risk factors for later drug injection or about the life course of injection once established including the influence of medical and social interventions. METHODS: Individuals thought to be drug injectors were identified through a single primary medical care facility in Edinburgh between 1980 and 2006 and flagged with the General Registry Office. From October 2005 - October 2007, these cases were traced and invited to undergo interview assessment covering early life experience, substance use, health and social histories. Age and sex matched controls for confirmed cases (alive and dead) were later recruited through the same health facility. Controls for living cases completed the same structured interview schedule. Data were also collected on cases and controls through linkage to routine primary care records, death registrations, hospital contact statistics and police and prison records. All interviews were conducted with the knowledge and permission of the current GP. RESULTS: The initial cohort size was 814. At start of follow up 227 had died. Of the remaining 587: 20 had no contact details and 5 had embarked from the UK; 40 declined participation; 38 did not respond to invitations; 14 were excluded by their GP on health or social grounds and 22 had their contact details withheld by administrative authorities. 448 were interviewed of whom 16 denied injection and were excluded. Of 191 dead cases with medical records 4 were excluded as their records contained no evidence of injection. 5 interviewed cases died before follow up was concluded though these individuals were counted as "live" cases. 1 control per case (dead and alive) was recruited. Linkage to Scottish Morbidity Records data (available from 1981 onwards) on general acute inpatient and day cases, mental health inpatient and day cases and cancer was provided by Information Services, NHS Scotland, for all cases interviewed and all dead cases. The Scottish Prison Service provided records for 198 (46%) of cases interviewed, 48 cases not interviewed and 34 (18%) of dead cases. For a sub-sample of 100 interviewees a search of the Lothian and Borders police database was made for official criminal records and 94 had criminal records. Data linkage for controls is ongoing. CONCLUSIONS: Injecting drug users recruited from a community setting can be successfully followed-up through interviews and record linkage. Information from injecting cases is being analysed in terms of injecting patterns and possible influences on these. Comparisons between cases and controls will allow identification of possibly modifiable early life risk factors for drug injection and will also clarify the burden of disease associated with injection and the influence on this of different health and social interventions.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Characterisation of Osteopontin in an In Vitro Model of Embryo Implantation

At the onset of pregnancy, embryo implantation is initiated by interactions between the endometrial epithelium and the outer trophectoderm cells of the blastocyst. Osteopontin (OPN) is expressed in the endometrium and is implicated in attachment and signalling roles at the embryo–epithelium interface. We have characterised OPN in the human endometrial epithelial Ishikawa cell line using three different monoclonal antibodies, revealing at least nine distinct molecular weight forms and a novel secretory pathway localisation in the apical domain induced by cell organisation into a confluent epithelial layer. Mouse blastocysts co-cultured with Ishikawa cell layers served to model embryo apposition, attachment and initial invasion at implantation. Exogenous OPN attenuated initial, weak embryo attachment to Ishikawa cells but did not affect the attainment of stable attachment. Notably, exogenous OPN inhibited embryonic invasion of the underlying cell layer, and this corresponded with altered expression of transcription factors associated with differentiation from trophectoderm (Gata2) to invasive trophoblast giant cells (Hand1). These data demonstrate the complexity of endometrial OPN forms and suggest that OPN regulates embryonic invasion at implantation by signalling to the trophectoder

Survival and cessation in injecting drug users: prospective observational study of outcomes and effect of opiate substitution treatment

Objectives To examine survival and long term cessation of injecting in a cohort of drug users and to assess the influence of opiate substitution treatment on these outcomes

The Need to Decide If All Estrogens Are Intrinsically Similar

We used gene expression profiling to investigate whether the molecular effects induced by estrogens of different provenance are intrinsically similar. In this article we show that the physiologic estrogen 17β-estradiol, the phytoestrogen genistein, and the synthetic estrogen diethylstilbestrol alter the expression of the same 179 genes in the intact immature mouse uterus under conditions where each chemical has produced an equivalent gravimetric and histologic uterotrophic effect, using the standard 3-day assay protocol. Data are also presented indicating the limitations associated with comparison of gene expression profiles for different chemicals at times before the uterotrophic effects are fully realized. We conclude that the case has yet to be made for regarding synthetic estrogens as presenting a unique human hazard compared with phytoestrogens and physiologic estrogens

Osmotic stress induces JNK-dependent embryo invasion in a model of implantation

In vitro culture during assisted reproduction technologies (ARTs) exposes pre-implantation embryos to environmental stressors, such as non-physiological nutritional, oxidative and osmotic conditions. The effects on subsequent implantation are not well understood but could contribute to poor ART efficiency and outcomes. We have used exposure to hyperosmolarity to investigate the effects of stress on the ability of embryos to interact with endometrial cells in an in vitro model. Culturing mouse blastocysts for 2 h in medium with osmolarity raised by 400 mosmol induced blastocoel collapse and re-expansion, but did not affect subsequent attachment to, or invasion of, the endometrial epithelial Ishikawa cell line. Inhibition of stress-responsive c-Jun N-terminal kinase (JNK) activity with SP600125 did not affect the intercellular interactions between these embryos and the epithelial cells. Four successive cycles of hyperosmotic stress at E5.5 had no effect on attachment, but promoted embryonic breaching of the epithelial cell layer by trophoblast giant cells in a JNK-dependent manner. These findings suggest that acute stress at the blastocyst stage may promote trophoblast breaching of the endometrial epithelium at implantation and implicates stress signalling through JNK in the process of trophectoderm differentiation into the invasive trophoblast necessary for the establishment of pregnancy. The data may lead to increased understanding of factors governing ART success rates and safety