Serum MMP-9 and SAA in the Diagnosis of Severe Pneumonia Caused by Radiotherapy of Esophageal Cancer

Objective. To explore the relationship and diagnostic value of serum MMP-9 and SAA in severe pneumonia (sCAP) caused by radiotherapy of esophageal cancer. Methods. A total of 144 esophageal cancer patients who underwent radiotherapy in our hospital from April 2016 to February 2018 were collected. Among them, 58 patients without radiation pneumonitis (RP) were in the control group, 49 patients with grade 1∼2 RP were in the radiation group, and 37 patients with sCAP were in the severe group. The levels of serum MMP-9 and SAA in every group of patients were detected. The ROC curve was used to determine the diagnostic value of serum MMP-9 and SAA in the diagnosis of RP and sCAP. The correlation between serum MMP-9 and SAA and the patient’s lung function indexes was analyzed, and the logistic single-factor and multivariate analyses were performed to analyze the factors of sCAP in esophageal cancer radiotherapy. Results. PaO2, FVC, and FEV1 decreased in RP and sCAP, and PaCO2, white blood cells, serum MMP-9, and SAA levels increased ( P < 0.05 ); serum MMP-9 and SAA were negatively correlated with lung function ( P < 0.05 ); the AUC of serum MMP-9 and SAA in RP was 0.833 and 0.823, respectively, and the AUC of the two combined diagnosis of RP was 0.919. The AUC of serum MMP-9 and SAA in sCAP was 0.809 and 0.797, respectively, and the AUC of both combined diagnosis of sCAP was 0.873; logistics multivariate analysis found that serum MMP-9, serum SAA, double lung V5, and V20 were independent risk factors for sCAP caused by radiotherapy for esophageal cancer ( P < 0.05 ). Conclusion. Serum MMP-9 and SAA increase in RP and sCAP and are negatively correlated with lung function in patients with pneumonia. They are independent risk factors for severe pneumonia caused by radiotherapy of esophageal cancer and have good diagnostic value.

Exosomes Derived From Adipose-Derived Mesenchymal Stem Cells Ameliorate Radiation-Induced Brain Injury by Activating the SIRT1 Pathway

ObjectiveStudies have shown that the therapeutic effects of mesenchymal stem cells (MSCs) are mediated in a paracrine manner, mainly through extracellular vesicles such as exosomes. Here, we designed a study to investigate whether exosomes derived from adipose-derived mesenchymal stem cells (ADMSC-Exos) had protective effects in a rat model of radiation-induced brain injury and in microglia.MethodsMale adult Sprague-Dawley (SD) rats were randomly divided into three groups: the control group, the radiation group (30 Gy), and the radiation + exosomes group (30 Gy + 100 ug exosomes). Meanwhile, microglia were divided into four groups: the control group, the radiation group (10 Gy), the radiation + exosomes group (10 Gy + 4 ug exosomes), and radiation + exosomes + EX527 group (10 Gy + 4 ug exosomes + 100 nM EX527). Tissue samples and the levels of oxidative stress and inflammatory factors in each group were compared.ResultsStatistical analysis showed that after irradiation, ADMSC-Exos intervention in vivo significantly reduced the levels of caspase-3, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and promoted the recovery of superoxide dismutase (SOD), catalase (CAT), IL-4, and IL-10. Moreover, ADMSC-Exos intervention inhibited microglial infiltration and promoted the expression of SIRT1. Furthermore, the results in vitro showed that the above effects of ADMSC-Exos could be reversed by SIRT-1 inhibitor EX527.ConclusionThis study demonstrated that ADMSC-Exos exerted protective effects against radiation-induced brain injury by reducing oxidative stress, inflammation and microglial infiltration via activating the SIRT1 pathway. ADMSC-Exos may serve as a promising therapeutic tool for radiation-induced brain injury.

Premature Ovarian Insufficiency (POI) Induced by Dynamic Intensity Modulated Radiation Therapy via P13K-AKT-FOXO3a in Rat Models

This study is aimed to investigate the mechanisms of radiation-induced mouse models of premature ovarian insufficiency (POI). Wistar female rats were grouped into the control, 3.2 Gy, 4.0 Gy, and 4.8 Gy groups. Overall ovarian functions were assessed with the H&E staining and ELISA. Proinflammatory cytokine secretion was analyzed ELISA, and the reactive oxygen species (ROS) levels were analyzed with immunohistochemistry. Protein expressions were analyzed by Western blot analysis. The 4.0 Gy and 4.8 Gy groups had significantly lower ovarian weight coefficients than the control and 3.2 Gy groups (after only one irradiation therapy). The 3.2 Gy radiation group induced periodic disturbance and hormone change at 4 weeks after radiation. In the 4.0 Gy and 4.8 Gy groups, the preantral follicles and antral follicles were decreased, while Atresia follicles were increased. E2 was decreased, while FSH and LH secretions were increased. The ovaries in the 4.0 Gy group were not completely atrophied, and some preantral follicles remained. Ovarian atrophy and follicular Atresia were found in the 4.8 Gy group. Inflammatory and oxidative markers were upregulated. PI3K and AKT were downregulated in the 4.0 Gy and 4.8 Gy groups, while FOXO3a was upregulated. Ovarian injuries may lead to oxidative damages and inflammatory injuries, downregulate the expression of P13k and Akt, upregulate the expression of FOXO3a, and lead to follicular atresia in the ovary.

Genetic and treatment risks for diabetes mellitus (DM) in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS) and St. Jude Lifetime (SJLIFE) cohorts.

10014 Background: Childhood cancer survivors face increased risk for DM, a polygenic trait also attributable to cancer treatment exposures, particularly abdominal radiation. We aimed to characterize the role of genetic and treatment risk factors for DM among two large cohorts of childhood cancer survivors. Methods: We performed a nested case-control genome-wide association study for DM managed with oral medications in the original CCSS cohort (diagnosed 1970-1986). Logistic regression was conducted in the total sample (N = 5083) and stratified by 1) European ancestry (EA) and 2) abdominal radiation. Replication of suggestive variants (P < 1×10-7) using Fisher’s exact test was performed in independent cohorts: i) CCSS expansion diagnosed 1987-1999 (N = 2588) and ii) SJLIFE diagnosed 1962-2012 (N = 2182). To evaluate the effect of cancer treatment on the background genetic predisposition to DM, we estimated standardized effect sizes (Z’) among EA survivors in each abdominal radiation group for 398 index variants from the largest population-based EA DM study. Radiation group Z’ estimates were compared using linear regression. Results: In the original CCSS cohort we identified nine variants associated with DM and provide further support for four linked variants in the ERCC6L2 locus. Among all survivors, the rs55849673-A allele was associated with increased odds for DM among survivors in the original CCSS cohort (minor allele frequency [MAF]-cases = 0.055; MAF-controls = 0.024; adjusted odds ratio [aOR] = 2.9, 95% CI: 2.0-4.2, P = 3.7×10-8). Allele frequencies were consistent in the CCSS expansion (MAF-cases = 0.075; MAF-controls = 0.028; P = 0.07) and SJLIFE (MAF-cases = 0.036; MAF-controls = 0.027; P = 0.5). Additionally, rs55849673-A estimates were consistent among EA survivors and stronger among survivors not treated with abdominal radiation (MAF-cases = 0.052; MAF-controls = 0.021; aOR = 3.6, P = 1.6×10-6). Notably, in the CCSS expansion all rs55849673-A EA carriers who developed DM did not receive abdominal radiation (MAF-cases = 0.1; MAF-controls = 0.026; P = 0.04). More broadly, the Z’ of population-based DM index variants were 78% lower in survivors treated with abdominal radiation than survivors not treated with abdominal radiation (beta = 0.22; P = 0.01), indicating the background genetic risk for DM may be altered by treatment. Conclusions: We provide evidence for a novel locus of DM in childhood cancer survivors. This locus is a regulatory region associated with expression of ERCC6L2, a gene implicated in an East Asian population-based DM study. Taken together, our findings support the overwhelming effect of abdominal radiation on DM risk in childhood cancer survivors, relative to other risk factors, and provide insight on a genetic locus that may be useful for DM risk prediction in the context of cancer treatment.

Effects of 1.5 and 4.3 GHz microwave radiation on cognitive function and hippocampal tissue structure in Wistar rats

Previous studies have shown that single-frequency microwave radiation can lead to cognitive decline in rats. However, few studies have focused on the combined effects of irradiation with different frequencies of microwaves. Our research aimed to investigate the effects of 1.5 GHz and 4.3 GHz microwave radiation, singly and in combination, on cognitive function and hippocampal tissue structure in rats. A total of 140 male Wistar rats were randomly divided into 4 groups: the S group (sham radiation group), L10 group (10 mW/cm2 1.5 GHz group), C10 group (10 mW/cm2 4.3 GHz band group) and LC10 group (10 mW/cm2 1.5 and 4.3 GHz multi-frequency radiation group). For 1–28 days after microwave radiation, we analyzed the average escape latency for the Morris water maze task, electroencephalograms, change in hippocampal tissue structure and ultrastructure, content of the Nissl body in the hippocampus, and activities of lactate dehydrogenase and succinate dehydrogenase. Compared to the S group, all exposure groups showed varying degrees of learning and memory decline and hippocampal structural damage. The results showed that 1.5 GHz and 4.3 GHz microwave radiation was able to induce cognitive impairment and hippocampal tissue damage in rats and combined radiation with both frequencies caused more serious injuries, but none of these damaging effects varied with microwave frequency.

Change in Physical Performance Correlates with Decline in Quality of Life and Frailty Status in Head and Neck Cancer Patients Undergoing Radiation with and without Chemotherapy

Patient-reported quality of life (QoL) metrics, frailty status, and physical functioning are emerging concepts in head and neck cancer (HNC) with implications on both treatment decision-making and prognosis. The impact of treatment-related functional decline on QoL and frailty has not been well-characterized in HNC and was the focus of this investigation. Methods: Patients who underwent radiation therapy for HNC from 2018 to 2020 were evaluated as a prospective observational cohort. Functional decline, QoL, and the frailty phenotype were measured via the Short Physical Performance Battery (SPPB), European Organization for Research and Treatment of Cancer (EORTC) qlq-C30, and Fried Frailty index, respectively. Results: A total of 106 HNC patients were included, 75 of which received concurrent chemoradiation therapy (CCRT) and 31 received radiation alone, both with and without surgery. There was a decrease in SPPB overall (p < 0.001) from the beginning to the end of treatment in the CCRT group but not the radiation group (p = 0.43). Change in overall SPPB points following treatment correlated with the decline in physical QoL for both groups (p < 0.05) as well as transition frail status in the CCRT group (p < 0.001) with a trend in the radiation group (p = 0.08). Conclusions: Change in SPPB correlates with QoL and transition to frailty status in patients undergoing definitive CCRT for HNC with similar trends in those receiving radiation alone. Decline in SPPB could potentially be useful in identification of those who may benefit from rehabilitation in future studies.

Protective Effect of Spirulina-Derived C-Phycocyanin against Ultraviolet B-Induced Damage in HaCaT Cells

Background and objectives: Reactive oxygen species (ROS) overwhelm the antioxidant defense system, induce oxidative stress, and increase matrix metalloproteinase (MMP) expression, resulting in skin aging. Thus, preventing ultraviolet B (UVB)-induced skin damage can attenuate skin aging. Spirulina (a biomass of cyanobacteria, also called blue-green algae) is comprised of prokaryotes, whereas microalgae are eukaryotes and are rich in phycocyanin, a powerful antioxidant. Materials and Methods: Here, we investigated the photoprotective effects of spirulina-derived C-phycocyanin (C-PC) against UVB radiation using keratinocytes (HaCaT cells). Results: UVB radiation increased MMP-1 and MMP-9 expression but decreased involucrin, filaggrin, and loricrin expression. C-PC showed no toxicity at concentrations of 5–80 μg/mL in terms of HaCaT cell viability. UVB-irradiated HaCaT cells had a 50.8% survival rate, which increased to 80.3% with C-PC treatment. MMP expression increased with UVB treatment, whereas MMP-1 and MMP-9 concentrations decreased with C-PC treatment. UVB reduced involucrin, filaggrin, and loricrin expression in HaCaT cells, but 80 μg/mL C-PC increased their expression by >25%. In the UVB radiation group, dichlorofluorescin diacetate fluorescence intensity in HaCaT cells increased by 81.6% compared with that in the control group, whereas ROS production was reduced by 51.2% and 55.1% upon treatment with 40 and 80 μg/mL C-PC, respectively. Conclusions: C-PC might reduce or prevent skin aging by reducing UVB irradiation-induced skin wrinkles and free radicals.

Curcumin protects radiation-induced liver damage in rats through the NF-κB signaling pathway

Background Curcumin has been demonstrated to exert anti-oxidant, anti-fibrotic, anti-inflammatory, and anti-cancer activities. This study was conducted to observe the effect and inner mechanism of curcumin in rats with radiation-induced liver damage (RILD). Methods Thirty SD rats were classified into Control, Radiation group and Curcumin (Cur) + Radiation group (n = 10 in each group). The changes in body weight of the rats were observed on the 3rd, 7th and 14th days after the treatment with curcumin. On the 14th day post treatment, the heart blood of the rats was drawn for measurement of liver function indices including total protein (TP), alanine aminotransfetase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) as well as aspartate aminotransfetase (AST). Subsequently, the rats were euthanized and liver tissues were taken to observe liver morphological changes using hematoxylin-eosin (HE), and to analyze apoptosis condition using transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assays. Meanwhile, the oxidative stress level in liver tissue homogenate was determined by biochemical analysis. The expression of nuclear factor kappa B (NF-κB) pathway-associated and apoptosis-associated proteins was detected using Western blot analysis, and the expression levels of inflammatory factors were measured by Enzyme-linked immunosorbent assay (ELISA). Results The reduced body weight was observed in rats of the Radiation group compared to the Control and Cur + Radiation groups on day 14. In the Radiation group, hepatic cell edema and inflammatory cell infiltration could be visible under the light microscope, and the hepatocytes presented with vacuolar degeneration. In the Cur + Radiation group, the hepatocytes swelled under the microscope, but the pathological changes were alleviated in comparison with the Radiation group. RILD rats with curcumin treatment presented with decreased ALT, AST, ALP, LDH, and maleicdialdehyde (MDA) levels, and elevated TP, superoxide dismutase (SOD), caspase activated DNase (CAD) and glutathione (GSH) levels. Apoptosis and inflammation in rats with RILD were up-regulated, and the NF-κB pathway was activated, but they were reversed after continuously intragastric administration of curcumin for 14 days. Conclusion Our study highlights that curcumin treatment reduces the liver damage caused by radiation through the inhibition of the NF-κB pathway.

Effect of Vitamin D supplementation on symmetric dimethyl arginine, asymmetric dimethyl arginine, homocysteine levels in rats being exposed to gamma radiation

Background: Radiation causes to damage on endothelial cells by increasing oxidative stress. Vitamin D is also a potent anti-oxidant that facilitates balanced mitochondrial activities, preventing oxidative stress-related protein oxidation, lipid peroxidation, and DNA damage. Aims and Objective: We aimed to investigate the potential effect of vitamin D supplementation on levels of Hcy (homocysteine), ADMA (Asymmetric Dimethyl Arginine), and SDMA (Symmetrical Dimethyl Arginine) which are admitted as endothelial dysfunction markers in rat models that are exposed to gamma radiation. Materials and Methods: Twentyfour female Wistar Albino rats were selected for the study. The mean weight of these rats were between 200 and 250 grams. Rats were fed with standard light (12 hours day light /12 hours dark), enough water (ad-libitum) at temperature (25ºC) for a total of 4 weeks. The rats were divided into 4 different groups and each group consisted of 6 rats. controlgroup (group I) did not receive any supplementation and not expose to gamma radiation), Group II was merely exposed to gamma radiation, Group III was exposed to gamma radiation and received vitamin D supplementation, and Group IV merely received vitamin D supplementation. Groups that are given vitamin D supplementation were fed by oral gavage at the same time and every day for one week. Finally, Group II and Group III were exposed to gammaradiation at the 8th day. After the completion of all processes, Vitamin D, ADMA, SDMA and Hcy levels were measured by HPLC (High-performance liquid chromatography) method. Results: When the results of Group II and Group III were compared with each other, we achieved merely statistical significance in vitamin D results (p=0.04) but did not other parameters (p>0.05). Conclusion: We observed that vitamin D supplementation did not any effect on SDMA, ADMA, and Hcy that accompany possible endothelial dysfunction after gamma radiation exposure.

Comparing Options for Heterotopic Ossification Prophylaxis following Elbow Trauma: A Systematic Review and Meta-Analysis

Introduction Heterotopic ossification (HO) can be a potentially serious and devastating complication following traumatic injury to the elbow. HO prophylaxis options include nonsteroidal anti-inflammatory drugs (NSAIDs) and radiation therapy (RT) but neither has been proven more effective. The purpose of this review is to compare effectiveness and outcomes between NSAID and RT prophylaxis for HO about the elbow following a traumatic injury. Materials and Methods We performed a systematic review of PubMed and Cochrane Library for cases of HO prophylaxis following elbow trauma utilizing PRISMA guidelines to determine the most effective form of prophylaxis. Outcomes of interest included recurrence of HO, range of motion (ROM), and Mayo elbow performance index (MEPI). A total of 36 articles and 826 elbows of which 203 received RT and 623 received NSAID were identified and included in the final analysis. Results Rates of HO formation or recurrence following elbow trauma were similar between radiation and NSAID prophylaxis (15.6% vs. 22.2%, respectively p = 0.457). ROM was similar in flexion and extension arc (109.0 degrees in radiation vs. 112.8 in NSAIDs, p = 0.459) and in pronation and supination arc (118.9 degrees radiation vs. 134.7 degrees NSAIDs, p = 0.322). MEPI scores were 79.19 in the radiation group and 88.82 in the NSAIDs group at the final follow-up. Conclusion There is no statistical difference in HO development, recurrence, or final ROM between NSAIDs and RT prophylaxis following trauma to the elbow. We recommend the choice of modality based on patient characteristics, cost, and surgeon preference. Level of Evidence Level III.