Krüppel-like factors family regulation of adipogenic markers genes in bovine cattle adipogenesis.

Intramuscular fat (IMF) content is a crucial determinant of meat quality traits in livestock. A network of transcription factors act in concert to regulate adipocyte formation and differentiation, which in turn influences intramuscular fat. Several genes and associated transcription factors have been reported to influence lipogenesis and adipogenesis during fetal and subsequent growth stage. Specifically in cattle, Krüppel-like factors (KLFs), which represents a family of transcription factors, have been reported to be involved in adipogenic differentiation and development. KLFs are a relatively large group of zinc-finger transcription factors that have a variety of functions in addition to adipogenesis. In mammals, the participation of KLFs in cell development and differentiation is well known. Specifically in the context of adipogenesis, KLFs function either as positive (KLF4, KLF5, KLF6, KLF8, KLF9, KLF10, KLF11, KLF12, KLF13, KLF14 and KLF15) or negative organizers (KLF2, KLF3 and KLF7), by a variety of different mechanisms such as crosstalk with C/EBP and PPARγ. In this review, we aim to summarize the potential functions of KLFs in regulating adipogenesis and associated pathways in cattle. Furthermore, the function of known bovine adipogenic marker genes, and associated transcription factors that regulate the expression of these marker genes is also summarized. Overall, this review will provide an overview of marker genes known to influence bovine adipogenesis and regulation of expression of these genes, to provide insights into leveraging these genes and transcription factors to enhance breeding programs, especially in the context of IMF deposition and meat quality.

Eugenol and carvacrol attenuate brain D-galactose-induced aging-related oxidative alterations in rats.

Aging represents the accumulation of progressive changes in a human being over time and can cover physical, psychological, and social changes. It is an oxidative stress-associated process that progresses with age. The antioxidant activity of either eugenol (EU) or carvacrol (CAR) for aging in rats induced by D-gal for 42 days was investigated in the current study using 10 and 20 mg of EU/kg/day/orally, while CAR was supplemented by 40 and 80 mg /kg/day/orally. Biochemical, mRNA expression, and histopathological assessments of brain samples evaluated the oxidative alterations induced by D-gal and the protective role of EU and CAR. Results showed that D-gal was causing oxidative alternation of the brain that was recognized via upregulation of p53 and p21 mRNA expression levels, as aging markers and Bax mRNA expression level, as an apoptotic marker. Also, the results observed alterations in the levels of biochemical markers as creatine phosphokinase (CPK) and triacylglycerol (TAG), besides, enhancement of brain antioxidant capacity. Finally, these results compared with the groups treated with EU and CAR to observe that the EU and CAR potentially attenuate these aging-related oxidative alterations in a dose-dependent manner. Finally, we can conclude that EU and CAR supplementations are considered promising natural protective compounds that could delay aging and maintain health.

Does a history of malignancy impact the survival of a subsequent endometrial adenocarcinoma? Should clinical trials eligibility criteria be revisited?

We aimed at finding the impact of prior malignancies on the survival of patients with endometrial adenocarcinoma using SEER database (from 1973 to 2014). We identified 127,988 patients who were diagnosed with endometrial adenocarcinoma (6485 had a prior malignancy), and we compared the overall and cancer-specific survival based on the presence or absence of a prior malignancy and the latency period between the two diagnoses using Kaplan-Meier test and Cox models. Adjusted cox models showed that a history of a prior malignancy neither affected the overall survival nor the cancer-specific survival of stage IV cases in all latency groups except the one diagnosed within 1 year of the first cancer. Therefore, there is no rational explanation for excluding stage IV endometrial adenocarcinoma patients with a prior malignancy from clinical trials except for the group that was diagnosed with endometrial adenocarcinoma within 1 year from the first cancer.Impact statementWhat is already known on this subject? Not enough evidence is found on the impact of prior malignancies on the survival of patients with subsequent endometrial adenocarcinoma.What do the results of this study add? History of a prior malignancy neither affects the overall survival of stage IV endometrial adenocarcinoma nor the cancer-specific survival. Only patients who had their second malignancy diagnosed within one year of the first malignancy should be excluded from clinical trials, while patients diagnosed within one to five years of the first cancer should be encouraged to enrol in clinical trials as they have an enhanced survival than patients without a history of malignancy.What are the implications of these findings for clinical practice and/or further research? We recommend that future researchers should consider including the aforementioned group of patients in their trials to achieve more accurate results and in order not to strip the patients of potential therapeutic benefits of enrolling in clinical trials.

Impact of prior malignancies on outcome of colorectal cancer; revisiting clinical trial eligibility criteria.

BACKGROUND: Most clinical trials on colorectal cancer (CRC) exclude cases who have history of a prior malignancy. However, no prior research studied this history's actual impact on the survival of CRC. In the paper, we study the effects of having a malignancy preceding CRC diagnosis on its survival outcomes. METHODS: CRC patients diagnosed during 1973-2008 were reviewed using the SEER 18 database. We calculated overall survival and cancer-specific survival of subsequent CRC, and more specifically stage IV CRC, using Kaplan-Meier test and adjusted Cox models. RESULTS: A total 550,325 CRC patients were reviewed, of whom 31,663 had history of a prior malignancy. The most commonly reported sites of a prior malignancy were: prostate, breast, urinary bladder, lung, and endometrium. Patients with history of a prior non-leukemic malignancy or history of a prior leukemia were found to have worse overall survival (HR = 1.165 95%CI = 1.148-1.183, P < 0.001) and (HR = 1.825 95%CI = 1.691-1.970, P < 0.001), respectively. However, CRC patients with history of a prior non-leukemic malignancy showed an improved colorectal cancer-specific survival (HR = .930 95%CI = .909-.952, P < 0.001). Analysis of stage IV CRC patients showed that patients with history of any non-leukemic malignancy did not have a significant change in overall survival. Whereas, patients with a prior leukemia showed a worse overall survival (HR = 1.535, 95%CI = 1.303-1.809, P < 0.001). When analyzed separately, right CRC and left CRC showed similar survival patterns. CONCLUSION: A prior malignancy before CRC -in general- can be associated with worse clinical survival outcomes. These worse outcomes are not observed in stage IV CRC. Considering these results when including/excluding stage IV CRC patients with prior malignancies in clinical trials may play help improve their generalizability.

Risk and survival of chronic myeloid leukemia after breast cancer: A population-based study.

BACKGROUND: We aimed to investigate the risk and survival of chronic myeloid leukemia (CML) after breast cancer (BC) diagnosis. METHODS: We used the Surveillance, Epidemiology, and End Results 'SEER' database. Females, diagnosed with BC between 1992 and 2014, were selected and followed for the development of CML after a 6-month latency period from BC diagnosis. We used the Multiple Primary Standardized Incidence Ratios session of the SEER*Stat software (version 8.3.4) to calculate the Observed/Expected (O/E) ratios with 95% confidence intervals (CI). To calculate the overall survival, we performed an unadjusted Kaplan-Meier analysis using the SPSS software. RESULTS: We included 474,866 females with BC, of which 178 were later diagnosed with CML. We found the risk of CML to increase significantly after BC diagnosis (O/E = 1.26, 95% CI: 1.08-1.45) and the risk was specifically higher within the first 5 years of diagnosis (O/E = 1.45, 95% CI: 1.16-1.8). When the risk was stratified by cancer stage, localized BC was associated with a significant increase in CML risk within 5 years of diagnosis (O/E = 1.4, 95% CI: 1.06-1.82), while regional BC was associated with a significant increase in CML risk after more than 5 years of diagnosis (O/E = 1.59, 95% CI: 1.09-2.25). Moreover, radiotherapy, chemotherapy, and presence of hormonal receptors were associated with a significant increase in CML risk in BC patients. The median overall survival of CML after BC was 28 months. CONCLUSION: Breast cancer patients have an increased risk of developing CML and further investigation is required to establish the causes of this finding.