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Mitochondrial DNA (mtDNA) mutations occur frequently in cancer cells, and some of them are often homoplasmic. Targeting such mtDNA mutations could be a new method for killing cancer cells with minimal impact on normal cells. Pyrrole-imidazole polyamides (PIPs) are cell-permeable minor groove binders that show sequence-specific binding to double-stranded DNA and inhibit the transcription of target genes. PIP conjugated with the lipophilic triphenylphosphonium (TPP) cation can be delivered to mitochondria without uptake into the nucleus. Here, we investigated the feasibility of the use of PIP-TPP to target a mtDNA mutation in order to kill cancer cells that harbor the mutation. We synthesized hairpin-type PIP-TPP targeting the A3243G mutation and examined its effects on the survival of HeLa cybrid cells with or without the mutation (HeLamtA3243G cells or HeLamtHeLa cells, respectively). A surface plasmon resonance assay demonstrated that PIP-TPP showed approximately 60-fold higher binding affinity for the mutant G-containing synthetic double-stranded DNA than for the wild-type A-containing DNA. When added to cells, it localized in mitochondria and induced mitochondrial reactive oxygen species production, extensive mitophagy, and apoptosis in HeLamtA3243G cells, while only slightly exerting these effects in HeLamtHeLa cells. These results suggest that PIP-TPPs targeting mtDNA mutations could be potential chemotherapeutic drugs to treat cancers without severe adverse effects.
Expansion of circulating NK cells has been related to pregnancy complications. This study aims at investigating several surface NK cell markers to identify a baseline inflammatory profile in women with recurrent pregnancy loss (iRPL) and recurrent implantation failure (iRIF).
Expression of NKp30, TIGIT, NKp46, and DNAM-1 on total peripheral blood NK subsets, regulatory (CD56
CD16
), and cytotoxic (CD56
CD16
) NK cells was measured.
Eighty-three women were recruited and classified into two groups, 58 women with RPL and 25 with RIF. A control group of 31 fertile women was included. Expression of NKp30 on cytNK was significantly higher in RPL (p=.019) and RIF (p<.001) than HC. TIGIT on cytNK cells was also higher in both RPL (p<.001) and RIF (p<.01). An optimal cutoff of 70% for NKp30
cytNK disclosed a sensitivity of 82%, a specificity of 55%, and 83% PPV for RPL diagnosis. A cutoff level of 83% for TIGIT
cytNK was chosen to discriminate between healthy controls and RPL women, with PPVation and validation in independent cohorts.Covalent organic frameworks (COFs) RIO-13, RIO-12, RIO-11, and RIO-11m were investigated towards their CO2 capture properties by thermogravimetric analysis at 1 atm and 40 °C. TLR2-IN-C29 order These microporous COFs bear in common the azine backbone composed of hydroxy-benzene moieties but differ in the relative number of hydroxyl groups present in each material. Thus, their sorption capacities were studied as a function of their textural and chemical properties. Their maximum CO2 uptake values showed a strong correlation with an increasing specific surface area, but that property alone could not fully explain the CO2 uptake data. Hence, the specific CO2 uptake, combined with DFT calculations, indicated that the relative number of hydroxyl groups in the COF backbone acts as an adsorption threshold, as the hydroxyl groups were indeed identified as relevant adsorption sites in all the studied COFs. Additionally, the best performing COF was thoroughly investigated, experimentally and theoretically, for its CO2 capture properties in a variety of CO2 concentrations and temperatures, and showed excellent isothermal recyclability up to 3 cycles.
The steady and continued increase of the Journal of Oral Pathology & Medicine's (JOPM) popularity prompted a bibliometric analysis of the journal. The purpose was to assess the significance and effect of the published research articles in the Journal from 1972 and 2020, aiding the identification of landmark articles. We performed a bibliometric analysis using the top 100 cited papers in the Journal of Oral Pathology & Medicine.
An extensive review of the Web of Science was undertaken. Standard information such as author details, affiliated institutions, publication year and the country of origin was recorded.
The top 100 cited articles in JOPM were assessed. The maximum and minimum number of citations in the top 100 articles was 1459 and 95, respectively. A total of 16790 citations were recorded for these 100 articles. Authors were affiliated to 28 different countries, 17 research articles from the UK and 12 from the USA. Other countries furnished seven or fewer articles.
This bibliometric analysis provides a synopsis of research published in the journal over a 48-year period. Recent interest in the journal shows a healthy increase in submissions and profile.
This bibliometric analysis provides a synopsis of research published in the journal over a 48-year period. Recent interest in the journal shows a healthy increase in submissions and profile.The trophic state of an aquatic body is influenced by many biotic and abiotic factors. When lots of parameters affect a phenomenon, such as eutrophication, it is difficult to distinguish which are the ones that affect the ecosystem the most. In this paper, we propose an alternative way for data analysis, in order to avoid complex systems with many variables. For the examined Mediterranean shallow lake, the studied parameters are water temperature (°C), ammonia (NH4 -N) (mg/L), dissolved oxygen (mg/L), turbidity (NTU), pH, conductivity (mS/cm), and chlorophyll-a (μg/L). We formed groups with the variables above based on fuzzy equivalence relations and from each group we chose the parameter influence the studied phenomenon the most. Numerical results of fuzzy linear regression showed strong agreement with the proposed method above and pH, NH4 -N, and dissolved oxygen are the variables influence this ecosystem more than the others. PRACTITIONER POINTS When having many parameters in a studied ecosystem, we propose a way we can distinguish the most representative ones, the parameters that influence more the phenomenon we study each time. Formation of groups in variables can be applied to many case studies in order to have a clear idea of our data and the relevance of each of them in our dependent one. Fuzzy linear regression can be used in order to check the final results and ensure that the equivalence relations are a such a good method used in the data analysis while the researchers save time in long procedures of analyzing parameters not very close involved to the phenomenon investigated every time.
Amphotericin B is a crucial agent in the management of serious systemic fungal infections. It is also known to be cytotoxic. In this study, we evaluated the effect of amphotericin B added to the preservation solution on islet yield during islet isolation.
Porcine pancreata were preserved in the preservation solution with or without amphotericin B (0.25μg/mL) for approximately 18hours at 4°C, and then islet isolation was performed. An optimized number (1750IE) of isolated islets from each group were transplanted into streptozotocin-induced diabetic mice. The culture of isolated islets and acinar tissue with amphotericin B was also evaluated.
The islet yield before and after purification in the amphotericin B (-) group was significantly higher than that in the amphotericin B (+) group. After islet transplantation into diabetic mice, blood glucose levels reached the normoglycemic range, with 50% and 0% of that of the diabetic mice in the amphotericin B (-) and amphotericin B (+) groups, respectively. In the culture study, amphotericin B was found to be cytotoxic to porcine islets and acinar tissue.
Amphotericin B added to the preservation solution deteriorates islet yield during porcine islet isolation. Thus, the use of amphotericin B should be considered carefully for the preservation of the pancreas for islet isolation and islet culture before islet transplantation.
Amphotericin B added to the preservation solution deteriorates islet yield during porcine islet isolation. Thus, the use of amphotericin B should be considered carefully for the preservation of the pancreas for islet isolation and islet culture before islet transplantation.Invasive species are a global threat to biodiversity, and understanding their history and biology is a major goal of invasion biology. Population-genetic approaches allow insights into these features, as population structure is shaped by factors such as invasion history (number, origin and age of introductions) and life-history traits (e.g., mating system, dispersal capability). We compared the relative importance of these factors by investigating two closely related ants, Tetramorium immigrans and Tetramorium tsushimae, that differ in their social structure and invasion history in North America. We used mitochondrial DNA sequences and microsatellite alleles to estimate the source and number of introduction events of the two species, and compared genetic structure among native and introduced populations. Genetic diversity of both species was strongly reduced in introduced populations, which also differed genetically from native populations. Genetic differentiation between ranges and the reduction in microsatellite diversity were more severe in the more recently introduced and supercolonial T. tsushimae. However, the loss of mitochondrial haplotype diversity was more pronounced in T. immigrans, which has single-queen colonies and was introduced earlier. Tetramorium immigrans was introduced at least twice from Western Europe to North America and once independently to South America. Its monogyny might have limited genetic diversity per introduction, but new mutations and successive introductions over a long time may have added to the gene pool in the introduced range. Polygyny in T. tsushimae probably facilitated the simultaneous introduction of several queens from a Japanese population to St. Louis, USA. In addition to identifying introduction pathways, our results reveal how social structure can influence the population-genetic consequences of founder events.
To assess the efficacy of combination of prostate-targeted treatment and metastasis-directed therapy for oligometastatic prostate cancer.
We retrospectively evaluated the clinical outcomes of synchronously diagnosed oligometastatic prostate cancer patients treated with external beam radiation therapy for the prostate and all metastatic lesions (≤3 lesions) at Kyoto University Hospital between January 2004 and April 2019. The prescribed dose was basically ≥70Gy for the prostate with or without whole pelvic irradiation, and ≥45Gy for the metastatic lesions. Clinical outcomes were compared with a contemporary cohort of 55 synchronous oligometastatic prostate cancer patients treated with the standard of care.
In total, 16 consecutive patients with synchronous oligometastatic prostate cancer were analyzed. The median follow-up period was 7.4years. The 8-year overall survival, prostate cancer-specific survival, biochemical failure-free, clinical failure-free and castration-resistant prostate cancer-free rates were 64.
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