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Breast cancer therapy options are limited due to its late diagnosis and poor prognosis. Doxorubicin is the fundamental therapy approach for this disease. Because chemotherapy has numerous adverse effects, the scope of the existing research was to appraise the synergetic effect of doxorubicin and naringin and explore the underlying mechanism. The cytotoxicity of doxorubicin and naringin on MCF-7 was monitored. Furthermore, the expression of STAT3 and JAK1 as well as the apoptotic and metastatic related genes (Bax, Bcl-2, Survivin, and VEGF) were conducted by immunoblotting assay and qRT-PCR. In addition, a wound healing test was utilized to appraise the migration and metastasis of MCF-7. Our results revealed that naringin and doxorubicin had a synergetic inhibitory influence on MCF-7 cells growth and migration. The synergetic action of doxorubicin and naringin effectively hindered the expression of STAT3, JAK1, Bcl-2, Survivin, and VEGF, with a boost in the level of Bax compared to cells treated with either doxorubicin or naringin. In conclusion, our findings imply that combining doxorubicin with naringin may be a favorable strategy for inhibiting the growth of breast cancer.

Background Immune checkpoint pathways play important roles in breast cancer (BC) pathogenesis and therapy. Methods Expression levels of programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), programmed death-ligand 1 (PD-L1), Forkhead box P3 (FOXP3), miR-155, and miR-195 were assessed in the peripheral blood of 90 BC patients compared to 30 healthy controls using quantitative real-time PCR (qRt-PCR). The plasma level of soluble MHC class I chain related-protein B (MIC-B) protein was assessed using the enzyme linked immunosorbent assay (ELISA) technique. The data were correlated to the clinico-pathological characteristics of the patients. Results There was a significant increase in the expression levels of PDL-1 [17.59 (3.24–123), p < 0.001], CTLA-4 [23.34 (1.3–1267), p = 0.006], PD-1 [10.25 (1–280), p  <  0.001], FOXP3 [11.5 (1–234.8), p = 0.001], miR-155 [87.3 (1.5–910), p < 0.001] in BC patients compared to normal controls. The miR-195 was significantly downregulated in BC patients [0.23 (0–0.98, p < 0.001]. The plasma level of MIC-B was significantly increased in the BC patients [0.941 (0.204–6.38) ng/ml], compared to the control group [0.351 (0.211–0.884) ng/mL, p < 0.00]. PDL-1, CTLA-4, PD-1, and FOXP3 achieved a specificity of 100% for distinguishing BC patients, at a sensitivity of 93.3%, 82.2%, 62.2%, and 71.1% respectively. The combined expression of PDL-1 and CTLA-4 scored a 100% sensitivity and 100% specificity for diagnosing BC (p < 0.001). The sensitivity, specificity, and AUC of miR-155 were 88.9%, 96.7%, and 0.934; respectively (p < 0.001). While those of miR-195 were 73.3%, 60%, and 0.716; respectively (p = 0.001). MIC-B expression showed a 77.8% sensitivity, 80% specificity, and 0.811 AUC at a cutoff of 1.17 ng/ml (p < 0.001). Combined expression of miR-155 and miR-195 achieved a sensitivity of 91.1%, a specificity of 96.7%, and AUC of 0.926 (p < 0.001). Multivariate analysis showed that PDL-1 (OR:13.825, p = 0.004), CTLA-4 (OR: 20.958, p = 0.010), PD-1(OR:10.550, p = 0.044), MIC-B (OR: 17.89, p = 0.003), miR-155 (OR: 211.356, P < 0.001), and miR-195(OR:0.006, P < 0.001) were considered as independent risk factors for BC. Conclusions The PB levels of PDL-1, CTLA-4, PD-1, FOXP3, MIC-B, miR-155, and miR-195 could be used as promising diagnostic markers for BC patients.

Chemoresistance and chemotherapy-related ovarian damage are well-reported in breast cancer (BC) young patients. Herein, the inhibition of the mitochondrial fission was invested to explore its chemosensitizing role in Paclitaxel (PTX)-resistant cells, and its ability to restore the ovarian integrity in mice receiving PTX or cisplatin chemotherapy. To establish these aims, PTX-resistance was generated in BC cells, which were treated with PTX in combination with Drp1 deficiency, via mdivi-1, or Drp1-specific siRNA transfection. Furthermore, the alterations in the ovarian structure and the endocrine-related hormones were explored in mice receiving repetitive doses of PTX or cisplatin. We found that combining PTX with mdivi-1 improved cell responsiveness to PTX, induced apoptosis- and autophagy-mediated cell death, and relieved cellular oxidative stress. Additionally, the expression of PCNA1 and cyclin B1 genes were downregulated, meanwhile, p53, p21, and mitochondrial fusion proteins (Mfu1&Mfu2) were increased. The in vivo investigations in mice demonstrated that PTX induced gonadotoxic damage similar to cisplatin, whereas dual treatment of mice with PTX+ mdivi-1 failed to restore their normal follicular count and the circulating levels of E2 and AMH hormones. These results suggested that combining Drp1 inhibition with PTX resensitized breast cancer cells to PTX but failed to offer enough protection against chemotherapy-related gonadotoxicity.

To date few reports have pointed out the role of circulating miRNAs in discriminating metastatic liver tumors from primary hepatocellular (HCC) tumors. Such discrimination will have significant therapeutic and prognostic implications. The purpose of this study was to evaluate the potential value of a panel of HCC-related circulating miRNAs (miR-142, miR-182, miR-200a, mir-210, miR-211, miR-302b, miR-324, miR-338, miR-340 and miR-1246) as noninvasive biomarkers for discriminating primary HCC from metastatic tumors in the liver.Methods The expression level of the selected miRNAs was quantified by quantitative real time PCR in 33 patients with HCC, 22 patients with metastatic tumors in the liver, and 30 healthy volunteers as control. Mann-Whitney U test was used to evaluate the difference in miRNAs expression between primary and metastatic liver tumors and to study the associations between their relative expression levels and the clinicopathological factors. Receiver operating characteristic curve was used to evaluate the diagnostic value of the individual miRNAs.Results Statistical analyses revealed a differential expression in the level of serum miR-210 and miR-1246 between the two groups of patients. The sensitivity and specificity of miR-210, for differentiating HCC from metastatic malignancies in the liver were found to be 73.7% and 64.28%, respectively. Whilst, of miR-1246 were 72.2% and 67.8%, respectively. In addition, the differential expression of the two miRNAs was also found to be associated with clinicopathological parameters in the two studied groups.Conclusions Serum miR-210 and miR-1246 have some diagnostic value for discriminating patients with metastatic tumors to patients with primary HCC

Background Hydroxyapatite (HAP) resembles the components of biological hard tissue. Recent research has been interested in the biomedical application of HAP nanoparticles (HAP-NPs) in cancer treatment, HAP-NPs have high cytotoxic activity against cancerous cells, in addition, they are nontoxic to healthy normal cells, biocompatible, biodegradable, and have a high absorption rate within the tissue. Therefore, this study evaluated HAP-NPs' antitumoral activity in Ehrlich solid carcinoma (ESC)-bearing mice, in addition, we examined the anticancer efficacy of combined treatment of a common chemotherapeutic drug such as Cisplatin (CDDP) and HAP-NPs in ESC-bearing mice. Methods Forty female mice were inoculated with 200 µl of diluted ascites fluid containing approximately two million viable cancer cells in the mice's left thigh, after 14 days of inoculation, the mice were distributed into four groups: 10 mice in each. ESC group was administrated distilled water, the HAP-NPs group was treated orally with 100 mg/kg of hydroxyapatite nanoparticles, the CDDP group was administrated intraperitoneally with 5 mg/kg of Cisplatin, the HAP-NPs + CDDP group was treated with both doses of hydroxyapatite and cisplatin, the animal treatment was conducted for 20 days. Antitumor activity was assessed for two durations after 10 and 20 days. DNA damage assessment was performed using comet assay in ESC, in addition, we measured the expression of the following genes ( P53, Bcl2, and Bax ,) using quantitative real-time PCR, and the apoptotic-related proteins (P53 and Ki-67) using immunohistochemical analysis. A histopathological examination of ESC was performed. Results The obtained data illustrated a promising anticancer activity of HAP-NPs, and the combined treatment of HAP-NPs and CDDP illustrated a higher anticancer efficacy. HAP-NPs, CDDP, and HAP-NPs + CDDP resulted in significant ( P  < 0.05) nucleic acid destruction, and significant ( P  < 0.05) overexpression of apoptotic-related genes ( P53, Bax , and Bcl2 ) and proteins (Ki-67 and P53), causing the tumor bulk to be greatly reduced in HAP-NPs, CDDP, and HAP-NPs + CDDP (1100, 570, and 450 mm 3 ), respectively, compared to ESC group was 2240 mm 3 . Conclusion Hydroxyapatite nanoparticles can provoke DNA damage and regulate apoptosis, selectively eliminating tumor cells. The co-administration of HAP-NPs and CDDP resulted in a synergistic enhancement of cisplatin activity within the tumor tissue.

Doxorubicin (DOX) is the cornerstone of chemotherapy. However, it has dose-dependent cardiotoxic events that limit its clinical use. This study was intended to investigate the efficiency of DOX as an anti-cancer against the MCF-7 cell line in the presence of diosmin (DIO) and to appraise the protective impact of DIO against DOX cardiotoxicity in vivo. In vitro study was carried out to establish the conservation of DOX cytotoxicity in the presence of DIO. In vivo study was conducted on 42 adult female Wistar rats that were equally allocated into 6 groups; control, DIO (100 mg/kg), DIO (200 mg/kg), DOX (20 mg/kg, single dose i.p.), DIO (100 mg/kg) + DOX, received DIO orally (100 mg/kg) for 30 days, then administrated with a single dose of DOX and DIO (200 mg/kg) + DOX, received DIO orally (200 mg/kg) for 30 days, then administrated with DOX. In vitro study showed preservation of cytotoxic activity of DOX on MCF-7 in the presence of DIO. In vivo study indicated that DOX altered electrocardiograph (ECG) parameters. Also, it yielded a significant rise in CK-MB, cTnT and LDH serum levels and cardiac contents of MDA, IL-1β; paralleled by a significant drop in cardiac IL-10 and SOD. Moreover, significant upregulation of Bax, TNF-α, and HIF-1α, in concomitant with significant downregulation of Bcl-2 mRNA in cardiac tissue have been recorded in the DOX group. Furthermore, histopathological description of cardiac tissues showed that DOX alters normal cardiac histoarchitecture. On the opposite side, DIO pretreatment could ameliorate ECG parameters, suppress IL-1β and enhanceIL-10, promote activity of SOD and repress MDA. Additionally, downregulation of Bax, TNF-α, HIF-1α and upregulation of Bcl-2 have been demonstrated in DIO-pretreated rats. Furthermore, the histopathological examination of cardiac tissues illustrated that DIO had a favorable impact on the protection of heart histoarchitecture. DIO is suggested for protection against acute cardiotoxicity caused by DOX without affecting antitumor activity.

Background Attention-deficit/hyperactivity disorder (ADHD) is a childhood neurodevelopmental disorder that persists into adulthood . ADHD is a well-known risk factor for substance use disorder (SUD). However, the actual contribution of comorbidity is largely unknown. The current study investigated the prevalence of ADHD in a sample of abstinent patients compared to healthy controls. Compared to 51 healthy controls, 51 patients seeking medical treatment for SUD were abstinent from any substance for at least 1 month, interviewed by the use of the ICD-10 symptom checklist, the Social Classification Scale, the Addiction Severity Index, Conners adult ADHD Rating Scales Self-Report (CAARS-S:L), and the Kiddie-Sads-Present and Lifetime Version (K-SADS-PL). Results Using CAARS-S:L, the ADHD index showed that 9 subjects (17.6%) were diagnosed with adult ADHD. Using K-SADS-PL, 8 of the participants (15.7%) were found to have an adult ADHD diagnosis. Lower scores of the ADHD index are related to increased patients’ age, while increased scores of the ADHD index are related to more alcohol-related problems of the patients. The strongest predicting factors of increased ADHD index were drug problems and legal status. Conclusions The current study provides evidence of an increased diagnosis of adult ADHD in patients with substance use disorder, regardless of the type of substance abuse.

Background Attention deficit hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder that can extend into adulthood with multiple reported neuroimaging abnormalities. The focus of this research was to assess white matter impairments in ADHD children’s fathers with and without potential adult ADHD to see if these differences are connected with the persistence of ADHD into adulthood . Results The occurrence rate of the potential adult ADHD diagnosis among fathers of children with ADHD was 60%. There were statistically significant differences between fathers with ADHD and the non-ADHD population, due to the fact that the mean FA of the left superior corona radiata and the right posterior corona radiata were lower in the ADHD group than in the non-ADHD group, while the FA of the ADHD group was significantly greater than that of the non-ADHD group in terms of the left and right anterior thalamic radiations, the right superior longitudinal fasciculus and the left anterior corona radiata. Conclusions We observed an increased prevalence of ADHD in fathers of children diagnosed with ADHD. Fathers with potential adult ADHD have a variety of white matter abnormalities that reflect the neurobiological basis of ADHD, even in sub-threshold cases. This may provide insight into the neuroanatomical locations associated with the maintenance of ADHD throughout adulthood.

Purpose. To evaluate the short-term effectiveness of infliximab in controlling ocular manifestations in Behçet’s Disease (BD) patients candidate for pars plana vitrectomy, if given in a regimen before and after the planned procedure. Patients and Methods. 30 eyes of 27 adult male BD patients with a mean age of 35.56 yrs presented with refractory posterior uveitis not responding to immunosuppressive drugs and candidate for vitrectomy were included. Infliximab was given in a dose of 5 mg/kg intravenous infusion once every two weeks for 3 treatment sessions before the intended vitrectomy followed by 3 treatment sessions at two-week intervals, after vitrectomy. Results. Improvement of ocular manifestations was noted in all eyes, with complete resolution in 26 eyes (87%). Visual acuity improved from 0.23 ± 0.11 to 0.38 ± 0.17 (p≤0.2), ESR decreased from 65.92 mm/hr ± 17.32 SD to 24.93 mm/hr ± 5.28 SD at the last treatment cycle (p≤0.1). The mean daily dose of systemic corticosteroids was tapered from 44.54 mg/d ± 2.89 to 8.48 mg/d ± 6.38 (p≤0.2), and no relapses were noted during the follow-up period. Conclusion. Infliximab may be safe and effective in controlling posterior uveitis and inducing remissions if given in a regimen before and after vitrecomy in BD patients.