BackgroundTraumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to substantial neuronal damage and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of thiscascade. In the current study, we tested the hypothesis that curcumin, a phytochemical compound with potent anti-inflammatory properties that is extracted from the rhizome Curcuma longa, alleviates acute inflammatory injury mediated by TLR4 following TBI.MethodsNeurological function, brain water content and cytokine levels were tested in TLR4-/- mice subjected to weight-drop contusion injury. Wild-type (WT) mice were injected intraperitoneally with different concentrations of curcumin or vehicle 15 minutes after TBI. At 24 hours post-injury, the activation of microglia/macrophages and TLR4 was detected by immunohistochemistry; neuronal apoptosis was measured by FJB and TUNEL staining; cytokines were assayed by ELISA; and TLR4, MyD88 and NF-κB levels were measured by Western blotting. In vitro, a co-culture system comprised of microglia and neurons was treated with curcumin following lipopolysaccharide (LPS) stimulation. TLR4 expression and morphological activation in microglia and morphological damage to neurons were detected by immunohistochemistry 24 hours post-stimulation.ResultsThe protein expression of TLR4 in pericontusional tissue reached a maximum at 24 hours post-TBI. Compared with WT mice, TLR4-/- mice showed attenuated functional impairment, brain edema and cytokine release post-TBI. In addition to improvement in the above aspects, 100 mg/kg curcumin treatment post-TBI significantly reduced the number of TLR4-positive microglia/macrophages as well as inflammatory mediator release and neuronal apoptosis in WT mice. Furthermore, Western blot analysis indicated that the levels of TLR4 and its known downstream effectors (MyD88, and NF-κB) were also decreased after curcumin treatment. Similar outcomes were observed in the microglia and neuron co-culture following treatment with curcumin after LPS stimulation. LPS increased TLR4 immunoreactivity and morphological activation in microglia and increased neuronal apoptosis, whereas curcumin normalized this upregulation. The increased protein levels of TLR4, MyD88 and NF-κB in microglia were attenuated by curcumin treatment.ConclusionsOur results suggest that post-injury, curcumin administration may improve patient outcome by reducing acute activation of microglia/macrophages and neuronal apoptosis through a mechanism involving the TLR4/MyD88/NF-κB signaling pathway in microglia/macrophages in TBI.

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Adjuvant chemotherapy may cause alterations in serum lipids in postoperative breast cancer (BC) patients, but the specific alterations caused by different chemotherapy regimens remain unclear. The aim of this study was to investigate the status of serum lipids pre- and post-chemotherapy and to compare the side effects of different chemotherapy regimens on serum lipid. We retrospectively analysed the lipid profiles of 1934 consecutive postoperative BC patients who received one of the following chemotherapy regimens: doxorubicin and cyclophosphamide followed by paclitaxel (AC-T); epirubicin and cyclophosphamide followed by paclitaxel (EC-T); cyclophosphamide and paclitaxel (TC); and fluorouracil, cyclophosphamide, and epirubicin (FEC). The levels of triglycerides (TG), total cholesterols (TC), and low-density lipoprotein (LDL-C) were significantly elevated in patients who received chemotherapy regimens above ( P < .001). With respect to different chemotherapy regimens, FEC had less side effects on lipid profiles (TG ( P = .006), high-density lipoprotein (HDL-C) ( P < .001), and LDL-C ( P < .001)) than TC regimen and AC-T and EC-T regimen. Also, the incidence of newly diagnosed dyslipidemia after chemotherapy was lower in FEC group than TC group and AC-T and EC-T group ( P < .001). Additionally, the magnitude of the alterations in lipid profiles (TG, TC, HDL-C, and LDL-C) was greater in premenopausal patients than that of the postmenopausal patients ( P = .004; P < .001; P = .002; P = .003, respectively). Moreover, after adjusting for multiple baseline covariates, anthracycline-plus-taxane-based regimens (AC-T and EC-T) were still statistically associated with a high level of TG ( P = .004) and a low level of HDL-C ( P = .033) after chemotherapy compared with FEC regimen. Also, body mass index (BMI) > 24 was associated with abnormal lipid profiles (TG, TC, HDL-C, LDL-C) post-chemotherapy compared with BMI ≤ 24 ( P < .001; P = .036; P = .012; P = .048, respectively). BC patients receiving chemotherapy may have elevated lipid profiles, and anthracycline-based regimen had less side effects on lipid profiles compared with regimens containing taxane. Therefore, it is necessary to take lipid metabolism into consideration when making chemotherapy decisions and dyslipidemia prevention and corresponding interventions are indispensable during the whole chemotherapy period.

Background. Cancer diagnosis entails substantial psychological distress and is associated with dramatically increased risks of suicidal behaviors. However, little is known about the suicide risk among cancer survivors who developed a second malignant neoplasm (SMN). Methods. Using the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study involving 7,824,709 patients with first malignant neoplasm (FMN). We measured the hazard ratios (HRs) of suicide death after receiving a SMN diagnosis using Cox proportional hazard models, as compared with patients with FMN. The comparison with the US population was achieved by calculating standardized mortality ratios (SMRs). Results. Totally 685,727 FMN patients received a diagnosis of SMN during follow-up, and we in total identified 10,930 and 937 suicide deaths among FMN and SMN patients, respectively. The HR of suicide deaths was 1.23 (95% confidence interval (CI), 1.14–1.31) after a SMN diagnosis, compared with FMN patients, after adjusting for sociodemographic factors, tumor characteristics, and cancer treatment. As compared with the general population, while both SMN and FMN patients suffered an increased risk of suicide deaths, the excess risk was higher among SMN patients than FMN patients (age-, sex-, and calendar-year-adjusted SMR 1.65 (95% CI 1.54–1.75) vs. 1.29 (95% CI 1.26–1.31); P difference < 0.0001 ). Notably, across different time periods, we observed the greatest risk elevation during the first 3 months after a cancer diagnosis. Conclusions. Compared with either patients with FMN or the general population, cancer survivors who received a SMN diagnosis were at increased risk of suicide death. The risk elevation was most prominent soon after the cancer diagnosis, highlighting the necessity of providing timely psychological support to cancer survivors with a SMN.