Novel Application of Localized Nanodelivery of Anti–Interleukin‐6 Protects Organ Transplant From Ischemia–Reperfusion Injuries

Ischemia–reperfusion injury (IRI) evokes intragraft inflammatory responses, which markedly augment alloimmune responses against the graft. Understanding the mechanisms underlying these responses is fundamental to develop therapeutic regimens to prevent/ameliorate organ IRI. Here, we demonstrate that IRI results in a marked increase in mitochondrial damage and autophagy in dendritic cells (DCs). While autophagy is a survival mechanism for ischemic DCs, it also augments their production of interleukin (IL)‐6. Allograft‐derived dendritic cells (ADDCs) lacking autophagy‐related gene 5 (Atg5) showed higher death rates posttransplantation. Transplanted ischemic hearts from CD11cCre/Atg5 conditional knockout mice showed marked reduction in intragraft expression of IL‐6 compared with controls. To antagonize the effect of IL‐6 locally in the heart, we synthesized novel anti–IL‐6 nanoparticles with capacity for controlled release of anti–IL‐6 over time. Compared with systemic delivery of anti–IL‐6, localized delivery of anti–IL‐6 significantly reduced chronic rejection with a markedly lower amount administered. Despite improved allograft histology, there were no changes to splenic T cell populations, illustrating the importance of local IL‐6 in driving chronic rejection after IRI. These data carry potential clinical significance by identifying an innovative, targeted strategy to manipulate organs before transplantation to diminish inflammation, leading to improved long‐term outcomes.     

Synergistic activity of lawsone methyl ether in combination with some antibiotics and artocarpin against methicillin-resistant Staphylococcus aureus, Candida albicans, and Trychophyton rubrum

Objective: One appealing strategy to overcome and prevent resistant problem is the use of combined two or more antibacterial substances. Lawsone methyl ether(LME) is the naphthoquinone found in the leaves of Impatiens balsamina. The objective of this study is to determine the interaction of LME with some antibiotics(ampicillin, tetracycline, norfloxacin, and clotrimazole) and a natural compound, artocarpin against methicillin-resistant Staphylococcus aureus(MRSA), Candida albicans, and Trychophyton rubrum.Methods: A broth microdilution method was used to determine the minimum inhibition concentration(MIC). Synergistic effects were evaluated at their own MIC using the checkerboard method and time-kill assay.Results: LME showed moderate antibacterial activity against MRSA with MIC value of 15.6 μg/mL, and exhibited strong antifungal activities against T. rubrum and C. albicans with MIC values of 7.8 and 3.9 μg/m L,respectively. The interaction of LME with the natural compound artocarpin against MRSA produced a synergy with fractional inhibitory concentration index(FICI) value of 0.31, while the combination of LME and clotrimazole exhibited synergy against C. albicans and T. rubrum with FICI values of 0.38 and 0.24, respectively. The time-kill assays confirmed that the compounds in combination enhanced their antimicrobial activities against the resistant microorganisms with different degrees.Conclusion: LME in combination with clotrimazole exhibited synergy effect against C. albicans and T.rubrum. In combination with artocarpin, it showed synergy effect against MRSA.     

Serum Circ‐FAF1/Circ‐ELP3: A novel potential biomarker for breast cancer diagnosis

BackgroundRecently, measurement of serum circular RNAs (circRNAs) as a non‐invasive tumor marker has been considered more. We designed the present study to investigate the diagnostic efficiency of serum Circ‐ELP3 and Circ‐FAF1, separately and simultaneously, for diagnosis of patients with breast cancer.MethodsSeventy‐eight female patients diagnosed as primary breast cancer participated in this study. We measured the level of circRNAs in serum specimens of the studied subjects. A receiver operating characteristic (ROC) curve was plotted and the diagnostic efficiency for both circRNAs was determined.ResultsCompared to non‐cancerous controls, Circ‐ELP3 was upregulated in breast cancer patients (p‐value = 0.004). On the other hand, serum Circ‐FAF1 was seen to be decreased in breast cancer patients than controls (p‐value = 0.001). According to ROC curve results, the area under the curve (AUC) for Circ‐ELP3 and Circ‐FAF1 was 0.733 and 0.787, respectively. Furthermore, the calculated sensitivity and specificity for Circ‐ELP3 and Circ‐FAF1 were 65, 64% and 77, 74%, respectively. Merging both circRNAs increased the diagnostic efficiency, with a better AUC, sensitivity and specificity values of 0.891, 96 and 62%, respectively.ConclusionBriefly, our results revealed the high diagnostic value for combined circRNAs panel, including Circ‐ELP3 and Circ‐FAF1 as a non‐invasive marker, in detection of breast carcinomas.     

Digital optical tomography system for dynamic breast imaging

Diffuse optical tomography has shown promising results as a tool for breast cancer screening and monitoring response to chemotherapy. Dynamic imaging of the transient response of the breast to an external stimulus, such as pressure or a respiratory maneuver, can provide additional information that can be used to detect tumors. We present a new digital continuous-wave optical tomography system designed to simultaneously image both breasts at fast frame rates and with a large number of sources and detectors. The system uses a master-slave digital signal processor-based detection architecture to achieve a dynamic range of 160 dB and a frame rate of 1.7 Hz with 32 sources, 64 detectors, and 4 wavelengths per breast. Included is a preliminary study of one healthy patient and two breast cancer patients showing the ability to identify an invasive carcinoma based on the hemodynamic response to a breath hold.     

Prediction of pharmacologically induced baroreflex sensitivity from local time and frequency domain indices of R-R interval and systolic blood pressure signals obtained during deep breathing

Pharmacological measurement of baroreflex sensitivity (BRS) is widely accepted and used in clinical practice. Following the introduction of pharmacologically induced BRS (p-BRS), alternative assessment methods eliminating the use of drugs were in the center of interest of the cardiovascular research community. In this study we investigated whether p-BRS using phenylephrine injection can be predicted from non-pharmacological time and frequency domain indices computed from electrocardiogram (ECG) and blood pressure (BP) data acquired during deep breathing. In this scheme, ECG and BP data were recorded from 16 subjects in a two-phase experiment. In the first phase the subjects performed irregular deep breaths and in the second phase the subjects received phenylephrine injection. From the first phase of the experiment, a large pool of predictors describing the local characteristic of beat-to-beat interval tachogram (RR) and systolic blood pressure (SBP) were extracted in time and frequency domains. A subset of these indices was selected using twelve subjects with an exhaustive search fused with a leave one subject out cross validation procedure. The selected indices were used to predict the p-BRS on the remaining four test subjects. A multivariate regression was used in all prediction steps. The algorithm achieved best prediction accuracy with only two features extracted from the deep breathing data, one from the frequency and the other from the time domain. The normalized L2-norm error was computed as 22.9% and the correlation coefficient was 0.97 (p=0.03). These results suggest that the p-BRS can be estimated from non-pharmacological indices computed from ECG and invasive BP data related to deep breathing.