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  • Munksgaard Horton posted an update 3 weeks, 4 days ago

    Triple negative breast cancer (TNBC) is an aggressive breast cancer with historically poor outcomes, primarily due to the lack of effective targeted therapies. The tumor molecular heterogeneity of TNBC has been well recognized, yet molecular subtype driven therapy remains lacking. While neoadjuvant anthracycline and taxane-based chemotherapy remains the standard of care for early stage TNBC, the optimal chemotherapy regimen is debatable. The addition of carboplatin to anthracycline, cyclophosphamide, and taxane (ACT) regimen is associated with improved complete pathologic response (pCR). Immune checkpoint inhibitor (ICI) combinations significantly increase pCR in TNBC. Increased tumor infiltrating lymphocyte (TILs) or the presence of DNA repair deficiency (DRD) mutation is associated with increased pCR. see more Other targets, such as poly-ADP-ribosyl polymerase inhibitors (PARPi) and Phosphatidylinositol-3-kinase/Protein Kinase B/mammalian target of rapamycin (PI3K-AKT-mTOR) pathway inhibitors, are being evaluated in the neoadjuvant setting. This review examines recent progress in neoadjuvant therapy of TNBC, including platinum, ICI, PARPi, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) pathway targeted therapies, and novel tumor microenvironment (TME) targeted therapy, in addition to biomarkers for the prediction of pCR.We investigated the association between head computed tomography (CT) scans and the risk of noncancer thyroid diseases in patients with minor head injury in a Taiwanese healthcare setting. For this retrospective population-based cohort study, the 2009-2013 Longitudinal Health Insurance Database was used to include patients with a minor head injury at admission or emergency visit between 2009 and 2013. Multivariate analysis with a multiple Cox regression model was applied to analyze the data. According to whether a CT scan was conducted within 14 days of admission, patients were divided into a CT scan group (n = 14,041) or a non-CT scan group (n = 34,684). No increased incidence of thyroid diseases was observed in the CT scan group regardless of the number of CT scans performed. The incidence rate ratio for one scan was 1.10 (95% confidence interval 0.94-1.29) and for two or more scans was 1.09 (95% confidence interval 0.93-1.28). In conclusion, this population-based cohort study showed that a head CT scan is not associated with increased risk of thyroid disease in patients with minor head injury. The short-term adverse effects on the thyroid could be mild when a regular CT scan is appropriately performed.In recent decades, cancer has been one of the leading causes of death worldwide. Despite advances in understanding the molecular basis of tumorigenesis, diagnosis, and clinical therapies, the discovery and development of effective drugs is an active and vital field in cancer research. Tetrahydrocurcumin is a major curcuminoid metabolite of curcumin, naturally occurring in turmeric. The interest in tetrahydrocurcumin research is increasing because it is superior to curcumin in its solubility in water, chemical stability, bioavailability, and anti-oxidative activity. Many in vitro and in vivo studies have revealed that tetrahydrocurcumin exerts anti-cancer effects through various mechanisms, including modulation of oxidative stress, xenobiotic detoxification, inflammation, proliferation, metastasis, programmed cell death, and immunity. Despite the pharmacological similarities between tetrahydrocurcumin and curcumin, the structure of tetrahydrocurcumin determines its distinct and specific molecular mechanism, thus making it a potential candidate for the prevention and treatment of cancers. However, the utility of tetrahydrocurcumin is yet to be evaluated as only limited pharmacokinetic and oral bioavailability studies have been performed. This review summarizes research on the anti-cancer properties of tetrahydrocurcumin and describes its mechanisms of action.Effects of isoquercitrin (IQ) on anaphylactic responses were examined in cardiovascular systems of experimental animals. In pithed rats, IQ at 30 and 100 mg/kg (intravenous) significantly blunted both the initial hypertensive and the ensuing hypotensive responses during anaphylaxis. Death rate and tachycardia were also significantly inhibited after the same IQ doses in these rats. In isolated guinea pig hearts, IQ infusion at 30-100 μg/mL markedly reduced anaphylaxis-related coronary flow decrease, contractile force change, and heart rate responses (both tachycardia and arrhythmia). Cardiac histamine and creatine kinase releases were similarly diminished by IQ during anaphylaxis in the isolated guinea pig hearts. In two different isolated guinea pig vasculatures, the pulmonary artery and mesenteric arterial bed, anaphylactic vasoconstriction was reduced by IQ 30 and 100 μg/mL. It was observed that IQ had a marked inhibitory effect on histamine release from rat mast cells, and this mechanism was suggested as the major anti-anaphylactic mechanism. Direct inhibition of histamine-induced muscle contraction did not seem to be relevant, but IQ treatment successfully repressed intracellular calcium influx/depletion in mast cells. Overall, this study provided evidence for the beneficial effect of IQ on cardiac anaphylaxis, thus suggesting its potential applications in the treatment and prevention of related diseases.Intersex, also known as hermaphroditism, is a serious hazard to animal husbandry and production. The mechanism of ovine intersex formation is not clear. Therefore, genome-wide resequencing on the only two intersex and two normal Lanzhou fat-tailed (LFT) sheep, an excellent but endangered Chinese indigenous sheep breed, was performed. Herein, the deletion of homologous sequences of the goat polled intersex syndrome (PIS) region (8787 bp, 247747059-247755846) on chromosome 1 of the LFT sheep was not the cause of the ovine intersex trait. By detecting the selective sweep regions, we found that the genes related to androgen biosynthesis and follicle stimulating hormone response items, such as steroid 5 alpha-reductase 2 (SRD5A2), steroid 5 alpha-reductase 3 (SRD5A3), and pro-apoptotic WT1 regulator (PAWR), may be involved in the formation of intersex traits. Furthermore, the copy number variations of the four regions, chr9 71660801-71662800, chr1 50776001-50778000, chr4 58119201-58121600, and chr16 778801-780800, may affect the expression of the zinc finger protein, FOG family member 2 (ZFPM2), LIM homeobox 8 (LHX8), inner mitochondrial membrane peptidase subunit 2 (IMMP2L) and slit guidance ligand 3 (SLIT3) genes, respectively, which contribute to the appearance of intersex traits.

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