Membrane Progesterone Receptor Alpha as a Potential Prognostic Biomarker for Breast Cancer Survival: A Retrospective Study

Classically, the actions of progesterone (P4) are attributed to the binding of nuclear progesterone receptor (PR) and subsequent activation of its downstream target genes. These mechanisms, however, are not applicable to PR– or basal phenotype breast cancer (BPBC) due to lack of PR in these cancers. Recently, the function of membrane progesterone receptor alpha (mPRα) in human BPBC cell lines was studied in our lab. We proposed that the signaling cascades of P4→mPRα pathway may play an essential role in controlling cell proliferation and epithelial mesenchymal transition (EMT) of breast cancer. Using human breast cancer tissue microarrays, we found in this study that the average intensity of mPRα expression, but not percentage of breast cancer with high level of mPRα expression (mPRα-HiEx), was significantly lower in the TNM stage 4 patients compared to those with TNM 1–3 patients; and both average intensities of mPRα expression and mPRα-HiEx rates were significantly higher in cancers negative for ER, as compared with those cancers with ER+. However, after adjusting for age at diagnosis and/or TNM stage, only average intensities of mPRα expression were associated with ER status. In addition, we found that the rates of mPRα-HiEx were significantly higher in cancers with epithelial growth factor receptor–1 (EGFR+) and high level of Ki67 expression, indicating positive correlation between mPRα over expression and EGFR or Ki67. Further analysis indicated that both mPRα-HiEx rate and average intensity of mPRα expression were significantly higher in HER2+ subtype cancers (i.e. HER2+ER–PR–) as compared to ER+ subtype cancers. These data support our hypothesis that P4 modulates the activities of the PI3K and cell proliferation pathways through the caveolar membrane bound growth factor receptors such as mPRα and growth factor receptors. Future large longitudinal studies with larger sample size and survival outcomes are necessary to confirm our findings

Low-energy properties and magnetization plateaus in a 2-leg mixed spin ladder

Using the density matrix renormalization group technique we investigate the low-energy properties and the magnetization plateau behavior in a 2-leg mixed spin ladder consisting of a spin-1/2 chain coupled with a spin-1 chain. The calculated results show that the system is in the same universality class as the spin-3/2 chain when the interchain coupling is strongly ferromagnetic, but the similarity between the two systems is less clear under other coupling conditions. We have identified two types of magnetization plateau phases. The calculation of the magnetization distribution on the spin-1/2 and the spin-1 chains on the ladder shows that one plateau phase is related to the partially magnetized valence-bond-solid state, and the other plateau state contains strongly coupled S=1 and s=1/2 spins on the rung.Comment: 6 pages with 8 eps figure

Prospects for microbial biodiesel production

As the demand for biofuels for transportation is increasing, it is necessary to develop technologies that will allow for low-cost production of biodiesel. Conventional biodiesel is mainly produced from vegetable oil by chemical transesterification. This production, however, has relatively low land-yield and is competing for agricultural land that can be used for food production. Therefore, there is an increasing interest in developing microbial fermentation processes for production of biodiesel as this will allow for the use of a wide range of raw-materials, including sugar cane, corn, and biomass. Production of biodiesel by microbial fermentation can be divided into two different approaches, (1) indirect biodiesel production from oleaginous microbes by in vitro transesterification, and (2) direct biodiesel production from redesigned cell factories. This work reviews both microbial approaches for renewable biodiesel production and evaluates the existing challenges in these two strategies

A retrospective study assessing the factors associated with visual outcome in retinal vein occlusion patients after anti-VEGF therapy

Background Retinal vein occlusion (RVO) is one of the most frequent retinal vascular diseases. In this study, we aimed to investigate the predictive factors of visual outcome for RVO patients who underwent anti-vascular endothelial growth factor (VEGF) therapy. Methods RVO patients who underwent anti-VEGF treatment were recruited in this study from January 2018 to June 2020. Clinical data and optical coherence tomography (OCT) parameters were retrospectively reviewed. Best-corrected visual acuity (BCVA) was examined at baseline and after anti-VEGF therapy. Predictive factors associated with visual outcome were assessed by logistic regression model. Treatment-related adverse events were also recorded. Results The average logMAR BCVA was 0.91 at baseline and 0.70 at final examination (P = 0.003). Among 75 patients, 41 experienced visual improvement were categorized as group A, the remaining 34 patients without improved vision were categorized as group B. Patients in group A demonstrated better visual outcomes, including decreased logMAR BCVA (average logMAR BCVA: 0.53 in group A vs. 0.91 in group B, P < 0.001) and central retinal thickness (CRT) (average CRT: 230.88 µm in group A vs. 404.97 µm in group B, P < 0.001) after anti-VEGF treatment. Multivariable analysis showed that injection frequency (odds ratio [OR], 2.623; 95% confidence interval [CI], [1.282–5.366]), hypertension (odds ratio [OR], 0.189; 95% CI [0.044–0.811]), hyperlipemia (odds ratio [OR], 0.195; 95% CI [0.040–0.941]) and external limiting membrane (ELM) disruption (odds ratio [OR], 0.148; 95% CI [0.032–0.691]) were all significantly associated with the visual outcome of RVO patients who underwent anti-VEGF treatment. In general, anti-VEGF therapy was feasible for all RVO patients, though the response to anti-VEGF was suboptimal in certain patients. Prognostic factors including injection frequency, hypertension, hyperlipemia and ELM disruption may all be useful to provide predictive information of visual outcome of RVO patients in response to anti-VEGF treatment

Thermal inactivation of Cronobacter sakazakii ATCC 29544 in powdered infant formula milk using thermostatic radio frequency

A 27.12 MHz thermostatic radio frequency (RF) system was employed to inactivate Cronobacter sakazakii in powdered infant formula milk. A proportional-integral-derivative controller achieved constant material temperature during the holding period. Hot air and similar dielectric material assistance were used to improve RF heating uniformity. The results showed that the microbial thermal resistance was reduced by increasing temperature (55–70 °C) and water activity (0.2–0.4 at 25 °C). Combined RF and hot air pasteurization (RF-HA) was more effective than single RF and material assistance due to better temperature uniformity. D70°C-value (23.3 min) of Cronobacter sakazakii at water activity of 0.2 from RF-HA was not significantly (P > 0.05) higher than that under hot water treatment (20.8 min), indicating that thermal effect led to microbial inactivation. Flow cytometry and transmission electron microscopy further confirmed that RF had no additional damage to cell membrane. The findings contribute to better understanding of RF pasteurization mechanism

A positive feedback between PDIA3P1 and OCT4 promotes the cancer stem cell properties of esophageal squamous cell carcinoma

Abstract Background Increasing evidence has indicated that long non-coding RNAs (lncRNAs) have been proven to regulate esophageal cancer progression. The lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P1) has been shown to promote cancer stem cell properties; however, its mechanism of action remains unclear. In this study, we investigated the regulation of esophageal cancer stem cell properties by the interaction of PDIA3P1 with proteins. Methods The GEPIA2 and Gene Expression Omnibus databases were used to analyze gene expression. PDIA3P1 expression in human esophageal squamous cell carcinoma (ESCC) tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Loss-of-function experiments were performed to determine the effects of PDIA3P1 on ESCC cell proliferation, migration, and invasion. The sphere formation assay, number of side population cells, and CD271 + /CD44 + cells were detected by flow cytometry to identify the cancer stem cell properties. RNA immunoprecipitation (RIP), RNA pull-down, co-immunoprecipitation (co-IP), dual luciferase reporter, and cleavage under targets and tagmentation (CUT&Tag) assays were performed to elucidate the underlying molecular mechanisms. Results PDIA3P1 expression was upregulated in ESCC cell lines and tissues. Functionally, higher PDIA3P1 expression promoted cell proliferation, invasion, and metastasis and inhibited apoptosis in esophageal cancer. Importantly, PDIA3P1 promoted cancer stem cell properties in ESCC. Mechanistically, PDIA3P1 interacted with and stabilized octamer-binding transcription factor 4 (OCT4) by eliminating its ubiquitination by the ubiquitinating enzyme WW domain-containing protein 2 (WWP2). Moreover, as a transcription factor, OCT4 bound to the PDIA3P1 promoter and promoted its transcription. Conclusions Our research revealed a novel mechanism by which a positive feedback loop exists between PDIA3P1 and OCT4. It also demonstrated that the PDIA3P1-WWP2-OCT4 loop is beneficial for promoting the cancer stem cell properties of ESCC. Owing to this regulatory relationship, the PDIA3P1-WWP2-OCT4-positive feedback loop might be used in the diagnosis and prognosis, as well as in the development of novel therapeutics for esophageal cancer

Association of mPRα expression with various clinicopathological characteristics and pathway biomarkers.

<p><i>Kruskal-Wallis</i> test, Chi-square test were used;</p>a<p><i>P</i> values calculated using Fisher’s exact test;</p>b<p>Additional adjusting for age, TNM stage;</p>c<p>TNM stage 0–3 vs. TNM stage 4;</p>d<p>TNM stage 0–2 vs. TNM stage 4;</p>e<p>There were two cases without grade information provided; <i>f</i> There were thirty five cases without the related information provided;</p