Tumors Established in a Defective Immune Environment Reprogram the Oncogenic Signaling Pathways to Escalate Tumor Antigenicity.

Tumors developed in immunocompromised hosts are more immunogenic. However, few studies have addressed the potential mechanisms underlying the high immunogenicity of tumors found in a suppressed immune system. Therefore, we aimed to elucidate the impacts of the immune system on tumor behaviors and immunogenicity sculpting. A murine colorectal adenocarcinoma cell line, CT26wt, was administrated into immunocompetent (BALB/c) and immunocompromised (NOD.SCID) mice, respectively. On day 11, the CT26 cells slowly progressed in the NOD.SCID mice compared to the BALB/c mice. We then performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) and analyzed the differentially expressed proteins (DEPs). The DEPs participated in numerous oncogenic pathways, PI3K/AKT/mTOR cell signaling, and the silencing of several tumor suppressors, such as PTEN and RBL1, during tumorigenesis. On day 34, the CT26/SCID tumors inversely became malignant counterparts; then the CT26/SCID tumors were harvested and re-inoculated into immunocompetent mice (CT26/SCID-Re tumors) to determine the immunogenicity. The CT26/SCID-Re tumor growth rate significantly decreased. Furthermore, increased infiltrations of dendritic cells and tumor-infiltrating T lymphocytes were found in the CT26/SCID-Re tumors. These findings suggest that immunogenic tumors might express multiple tumor rejection antigens, unlike wild-type tumors, and attract more immune cells, therefore decreasing the growth rate. Collectively, our study first revealed that in immunodeficient hosts, tumor suppressors were silenced and oncogenic signaling pathways were changed during the initial phase of tumor development. With tumor progression, the tumor antigens were overexpressed, exhibiting elevated immunogenicity. This study offers a hint on the mechanisms of tumorigenesis and provides a niche for investigating the interaction between host immunity and cancer development.

Joint association of physical activity and diet quality with dyslipidemia: a cross-sectional study in Western China.

OBJECTIVE: This study aims to investigate the prevalence of dyslipidemia and assess the joint association of physical activity (PA) and diet quality on dyslipidemia risk in urban areas of Xinjiang. METHODS: Conducted from July 2019 to September 2021 in Xinjiang, China, this cross-sectional study involved 11,855 participants (mean age 47.1 ± 9.4 years, 53.1% male). Standard methods were used to measure plasma cholesterol levels, and validated questionnaires were employed to evaluate dietary habits and PA. The definition of dyslipidemia is based on 2023 Chinese guidelines for lipid management. PA was divided into guideline-recommended moderate-to-vigorous physical activity (MVPA) and non-MVPA, following World Health Organization guidelines. The Food Frequency Questionnaire was used to obtain the intake frequency of each dietary term. Each item was scored based on consumption frequency and divided into three groups (good, intermediate, and poor) based on total dietary score. Multivariate logistic regression analysis was performed to identify dyslipidemia risk factors, as well as the joint association of PA and diet quality. RESULTS: Dyslipidemia prevalence among urban adults in Xinjiang was 39.3%, with notable sex disparities (52.6% in males vs. 24.3% in females, P < 0.001). Among participants with dyslipidemia, the awareness, treatment and control rates were 6.9%, 3.1%, and 1.9%, respectively. A significant multiplicative interaction between PA and diet quality is associated with dyslipidemia (P for interaction < 0.05). Less PA and poor diet quality were associated with an increased odds of dyslipidemia. Even individuals with poor (OR = 1.464, 95% CI: 1.106-1.939) or intermediate (OR = 1.229, 95% CI: 1.003-1.505) diet quality but adhering to recommended MVPA had lower odds of dyslipidemia compared to those with good diet quality but inadequate MVPA (OR = 1.510, 95% CI: 1.252-1.821). CONCLUSIONS: Dyslipidemia prevalence was 39.3% in urban adults in Xinjiang, with limited awareness, treatment, and control. Following guideline-recommended MVPA and maintaining good diet quality were protective against dyslipidemia. Low levels of PA associated with a higher prevalence of dyslipidemia, even in individuals with good diet quality.

Canine diffuse large b-cell lymphoma downregulates the activity of CD8 + T-cells through tumor-derived extracellular vesicles.

BACKGROUND: Tumor-derived extracellular vesicles (EVs) have been proposed as the essential mediator between host immunity and cancer development. These EVs conduct cellular communication to facilitate tumor growth, enable invasion and metastasis, and shape the favorable tumor microenvironment. Lymphoma is one of the most common hematological malignancies in humans and dogs. Effective T-cell responses are required for the control of these malignancies. However, the immune crosstalk between CD8 + T-cells, which dominates anti-tumor responses, and canine lymphoma has rarely been described. METHODS: This study investigates the immune manipulating effects of EVs, produced from the clinical cases and cell line of canine B cell lymphoma, on CD8 + T-cells isolated from canine donors. RESULTS: Lymphoma-derived EVs lead to the apoptosis of CD8 + T-cells. Furthermore, EVs trigger the overexpression of CTLA-4 on CD8 + T-cells, which indicates that EV blockade could serve as a potential therapeutic strategy for lymphoma patients. Notably, EVs transform the CD8 + T-cells into regulatory phenotypes by upregulating their PD-1, PD-L1, and FoxP3 mRNA expression. The regulatory CD8 + T-cells secret the panel of inhibitory cytokines and angiogenic factors and thus create a pro-tumorigenic microenvironment. CONCLUSION: In summary, the current study demonstrated that the EVs derived from canine B cell lymphoma impaired the anti-tumor activity of CD8 + T-cells and manipulated the possible induction of regulatory CD8 + T-cells to fail the activation of host cellular immunity.

Increased plasma DR-70 (fibrinogen-fibrin degradation products) concentrations as a diagnostic biomarker in dogs with neoplasms.

BACKGROUND: Tumor biomarkers have used widely in clinical oncology in human medicine. Only a few studies have evaluated the clinical utility of tumor biomarkers for veterinary medicine. A test for fibrinogen and fibrin degradation products (DR-70) has been proposed as an ideal biomarker for tumors in humans. The clinical value of DR-70 for veterinary medicine however has yet to be determined. OBJECTIVES: Investigate the diagnostic value of DR-70 concentrations by comparing them between healthy dogs and dogs with tumors. ANIMALS: Two hundred sixty-three dogs with different types of tumors were included. Sixty healthy dogs also were recruited for comparison. METHODS: The DR-70 concentrations were measured in all recruited individuals by ELISA. Clinical conditions were categorized based on histopathology, cytology, ultrasound examination, radiology, clinical findings, and a combination of these tests. RESULTS: The median concentration of DR-70 was 2.130 ± 0.868 µg/mL in dogs with tumors, which was significantly higher than in healthy dogs (1.202 ± 0.610 µg/mL; P < .0001). With a cut-off of 1.514 µg/mL, the sensitivity and specificity of DR-70 were 84.03% and 78.33%, respectively. The area under curve was 0.883. The DR-70 concentration can be an effective tumor biomarker in veterinary medicine. CONCLUSIONS AND CLINICAL IMPORTANCE: Increased DR-70 concentrations were not affected by tumor type, sex, age, or body weight. However, in dogs with metastatic mast cell tumors and oral malignant melanoma, DR-70 concentrations were significantly increased. Additional studies, including more dogs with nonneoplastic diseases, are needed to further evaluate the usefulness of DR-70 as a tumor biomarker.

[Mechanism of Salinization of Shallow Groundwater in Taocheng District, Hengshui City].

In order to understand the characteristics and origin of groundwater salinization in Taocheng district of Hengshui City, the recharge and salinization procession of shallow groundwater were analyzed with isotopic and geochemical data of the shallow groundwater (buried depth ≤ 100 m) and the soluble salt in boreholes. The results showed that the shallow groundwater was weak alkaline salt water, with the total dissolved solid (TDS) in the groundwater ranging from 176.06 to 17569.65 mg·L-1and the soil total salinity in unconsolidated sediments ranging from 1.830 to 6.509 g·kg-1. The hydrochemical types were mainly SO4·Cl-Na·Mg and Cl·SO4-Na·Ca in the shallow groundwater and the soluble salt. The main recharge resource of shallow groundwater was precipitation with different geological periods. The hydrochemical compositions of shallow groundwater mainly came from the dissolution of halite and sulfate weathering and experienced intense evaporation and the reduction environment. Meanwhile, the groundwater salinization was barely affected by human activities and seawater intrusion.

Shape Dependence of Silver-Nanoparticle-Mediated Synthesis of Gold Nanoclusters with Small Molecules as Capping Ligands.

In this study, differently shaped silver nanoparticles used for the synthesis of gold nanoclusters with small capping ligands were demonstrated. Silver nanoparticles provide a reaction platform that plays dual roles in the formation of Au NCs. One is to reduce gold ions and the other is to attract capping ligands to the surface of nanoparticles. The binding of capping ligands to the AgNP surface creates a restricted space on the surface while gold ions are being reduced by the particles. Four different shapes of AgNPs were prepared and used to examine whether or not this approach is dependent on the morphology of AgNPs. Quasi-spherical AgNPs and silver nanoplates showed excellent results when they were used to synthesize Au NCs. Spherical AgNPs and triangular nanoplates exhibited limited synthesis of Au NCs. TEM images demonstrated that Au NCs were transiently assembled on the surface of silver nanoparticles in the method. The formation of Au NCs was observed on the whole surface of the QS-AgNPs if the synthesis of Au NCs was mediated by QS-AgNPs. In contrast, formation of Au NCs was only observed on the edges and corners of AgNPts if the synthesis of Au NCs was mediated by AgNPts. All of the synthesized Au NCs emitted bright red fluorescence under UV-box irradiation. The synthesized Au NCs displayed similar fluorescent properties, including quantum yields and excitation and emission wavelengths.

[Hydrogen and Oxygen Isotopic Characteristics of Different Water and Indicative Significance in Baiyangdian Lake].

In order to better understand the water cycle processes in Baiyangdian Lake, samples for precipitation, river water, lake water, and groundwater were collected in 2020 via the analysis of oxygen and hydrogen isotopes and the total dissolved solids. A combined approach including correlation analysis, end-member modeling, and evaporation modeling was used to identify hydrogen and oxygen isotopic characteristics of different water types and their indicative significance to evaporation, hydrodynamics, and lake-groundwater interactions. The results showed that the compositions of hydrogen and oxygen isotopes in surface water and groundwater differed from each other. The average values of δD and δ18O were the highest in samples from lake water in June, secondary for lake water in October, and the lightest in groundwater. The slope of the lake water line was lower than that of the local meteoric water line, which could be attributed to a greater evaporative enrichment in lake water. The water loss ratio was estimated to be 18.8%-42.3% in June and 2.7%-30.3% in October by applying an evaporation model using deuterium excess. Lake water isotopes exhibited highly spatial heterogeneity, which indicated that Baiyangdian Lake was a poor-mixed lake controlled by the complex hydrodynamic conditions. The values of δD and δ18O were lighter around the estuary area and higher in the district far from the estuary. Although the main water isotopes in areas such as channels had a short residence time, the spatial differences in lake water isotopes were not remarkable, which suggested that the well-mixed conditions of the lake water contributed to reducing the heterogeneity of the lake water isotopic compositions on a spatial scale. The contribution ratios of lake leakage to groundwater were 0-91.7% and varied spatially. It had a negative relationship with the buried depth of groundwater and the distance to the lakeshore. No obvious relationship was found between lake leakage magnitude and groundwater level gradient. This study could provide a theoretical basis and technical support for the sustainable development of water resources and ecological environment protection in Baiyangdian Lake.

Lipid accumulation product as useful predictors of stroke: A correlation analysis between lipid accumulation index/cerebral vascular hemodynamics indexes and risk factors of stroke in 3264 people undergoing physical examination in Xinjiang.

OBJECTIVE: To investigate the relationship between lipid accumulation index and cerebral hemodynamic integral value in 3264 people undergoing physical examination, so as to analyze the correlation between different lipid accumulation product index (LAP) levels and stroke risk factors. METHODS: This cross-sectional study was conducted from January to December 2019 on 3264 adults at the age of 19 to 85 living in Urumqi, Xinjiang. The stroke related risk factors were evaluated by the questionnaire survey. The enrolled subjects were divided into Q1 group (n = 817), Q2 group (n = 815), Q3 group (n = 816) and Q4 group (n = 816) according to the quartile site at a low-to-high-score manner. RESULTS: The proportion of males was significantly higher than that of females in Q2, Q3, and Q4 groups. The proportion of middle-aged people and the elderly in Q2, Q3, and Q4 groups was significantly higher than that of youths (P < .05). The proportion of patients with history of hypertension, hyperlipidemia, physical inactivity, and smoking, and the levels of systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, high-density cholesterol, low-density cholesterol, triglyceride, body mass index, waist circumference increased with the increase of LAP level in different groups (P < .05). On both sides of the cerebral hemodynamic integral value (CVHI) index, Vmean, Vmax, Vmin showed a decreasing trend whereas peripheral resistance, pulse velocity, Zcv, dynamic resistance, critical pressure level, difference between diastolic and critical pressure showed an increase trend with the increase of LAP level. The normal rate of CVHI in 4 groups (>75 points) was 97.4%, 89.7%, 87.0, and 80.8%, respectively, showing a decreasing trend. Logistic regression results showed that the higher the LAP, the higher the abnormal risk of CVHI. CONCLUSION: There is a positive correlation between LAP and CVHI, the higher the LAP, the higher the risk of CVHI abnormality, which should be concerned seriously.

Xenograft cancer vaccines prepared from immunodeficient mice increase tumor antigen diversity and host T cell efficiency against colorectal cancers.

Autologous cancer vaccines (ACVs) are a desirable approach for personalized medicine, but the efficiency of ACVs remains unsatisfactory due to their low immunogenicity. This study developed a platform that can enhance the immunogenicity of ACVs by transplanting the tumors into immunodeficient mice. The CT26 cell line was inoculated into severe combined immunodeficient mice (SCID) for vaccine preparation where escalates tumor development, subsequently diversifying the tumor antigenic topology. CT26/SCID cancer vaccines significantly inhibited tumor growth, increased the amount of tumor infiltrating lymphocytes, and triggered Th-1 predominant immune responses. Tumor antigenic profiles of CT26/SCID cells were further analyzed by liquid chromatography-tandem mass spectrometry. Compared to CT26 parental cells, a total of 428 differentially expressed proteins (DEPs) were detected. These DEPs revealed that CT26/SCID cells overexpressed several novel therapeutic targets, including KNG1, apoA-I and, ß2-GPI, which can trigger cytotoxic T cells towards Th-1 predominant immune responses and directly suppress proliferation in tumors. CT26/SCID cancer vaccines can be easily manufactured, while traits of triggering stronger antigen-specific Th-1 immune activity against tumors, are retained. Results of this study provide an effective proof-of-concept of an ACV for personalized cancer immunotherapy.

Acute and chronic infection of H. pylori caused the difference in apoptosis of gastric epithelial cells.

Helicobacter pylori (H. pylori) is one of the most important pathogenic bacteria associated with various gastrointestinal diseases. At present, its apoptotic or antiapoptotic mechanism on gastric epithelial cells remains unknown and needs further illustrated. In this study, acute infection model (H. pylori and GES-1 cells were co-cultured for 24 h at a multiplicity of infection MOI of 100:1) and chronic infection model (GES-1 cells were infected repeatedly every 24 h at a multiplicity of infection MOI of 100:1 for approximately 8 weeks) were established, respectively. the chronic H. pylori infected GES-1 cells underwent a typically morphological change and Western Blot results showed that there was slight decrease in expression of E-cadherin, and obvious increase in expression of Vimentin. Apoptosis of these two models were analyzed by flow cytometry compared with the control cells, meanwhile, apoptosis associated markers (Bcl-xL, Bcl-2, Bax, etc) were detected by Western blot, additional in clinical H. pylori-positive gastric cancer tissues. Results showed that compared with the control cells, acute infection of H. pylori significantly accelerated the apoptosis of GES-1, increased the expression of Bax and Cleaved caspase-3, down-regulated expression of Bcl-xL and Bcl-2. Moreover, an opposite result was found in chronic infection of model and clinical gastric cancer tissues, and enhanced expression of NF-κB p65. Taken together, these findings suggest that H. pylori infection plays differential effects on apoptosis of gastric epithelial cells.

Lactobacillus fermentum KP-3-fermented ginseng ameliorates alcohol-induced liver disease in C57BL/6N mice through the AMPK and MAPK pathways.

Panax ginseng was fermented using Lactobacillus fermentum KP-3, and the levels of the minor ginsenosides were measured. Then, the effect of fermented ginseng on alcohol-induced liver injury was investigated. C57BL/6N mice were randomly assigned to 4 groups: pair fed (PF), alcohol fed (AF), alcohol with non-fermented ginseng (AF + NFG) and alcohol with fermented ginseng (AF + FG) groups. After treatment for 8 weeks, fermented ginseng intervention significantly reduced the levels of serum ALT, AST, LPS, TG and TC compared with the AF group. The western-blotting results showed that fermented ginseng activated the adenosine-monophosphate-activated protein kinase (AMPK) pathway to inhibit de novo lipogenesis in the liver and inhibited phosphorylation of p38 through the mitogen-activated protein kinase (MAPK) pathway to alleviate hepatic inflammation, and these effects were superior than those of non-fermented ginseng. Furthermore, fermented ginseng reduced alcohol-induced liver oxidative damage by upregulating the levels of antioxidant enzymes. These findings suggested that the L. fermentum KP-3-fermented ginseng product may be used as a potential dietary nutraceutical for alleviating alcoholic liver injury.

Conceptualization, Development and Psychometric Evaluations of a New Medication-Related Health Literacy Instrument: The Chinese Medication Literacy Measurement.

There is a need for valid and reliable instruments to focus on medication aspects of health literacy and help healthcare professionals address patients' barriers to medication use. This cross-sectional study describes the conceptualization, development, and psychometric properties of the first Chinese Medication Literacy Measurement (ChMLM) to assess the level of health literacy on medication use. The 17-item ChMLM (ChMLM-17) and its short form, 13-item ChMLM (ChMLM-13), consist of four sections (vocabulary, over-the-counter labels, prescription labels, and advertisements) to cover six domains of medication-related health literacy. Multistage stratified quota sampling was attempted to recruit a representative sample in Taiwan. Receiver operating characteristic curves were used to identify the cut-off point for differentiating high and low medication literacy. Psychometric analyses were performed (n = 1410) to assess the reliability and validity separately on all samples and sociodemographic subgroups. The 17- and 13-item versions both had high construct validity among all patients and patients with low medication literacy. The developed ChMLM-17 and ChMLM-13 is expected to help healthcare providers and researchers to accurately measure medication-related health literacy and improve medication use in the real-world practice.

Potential enhancement of host immunity and anti-tumor efficacy of nanoscale curcumin and resveratrol in colorectal cancers by modulated electro- hyperthermia.

BACKGROUND: Modulated electro-hyperthermia (mEHT) is a form of hyperthermia used in cancer treatment. mEHT has demonstrated the ability to activate host immunity by inducing the release of heat shock proteins, triggering apoptosis, and destroying the integrity of cell membranes to enhance cellular uptake of chemo-drugs in tumor cells. Both curcumin and resveratrol are phytochemicals that function as effective antioxidants, immune activators, and potential inhibitors of tumor development. However, poor bioavailability is a major obstacle for use in clinical cancer treatment. METHODS: This purpose of this study was to investigate whether mEHT can increase anti-cancer efficacy of nanosized curcumin and resveratrol in in vitro and in vivo models. The in vitro study included cell proliferation assay, cell cycle, and apoptosis analysis. Serum concentration was analyzed for the absorption of curcumin and resveratrol in SD rat model. The in vivo CT26/BALB/c animal tumor model was used for validating the safety, tumor growth curve, and immune cell infiltration within tumor tissues after combined mEHT/curcumin/resveratrol treatment. RESULTS: The results indicate co-treatment of mEHT with nano-curcumin and resveratrol significantly induced cell cycle arrest and apoptosis of CT26 cells. The serum concentrations of curcumin and resveratrol were significantly elevated when mEHT was applied. The combination also inhibited the growth of CT26 colon cancer by inducing apoptosis and HSP70 expression of tumor cells while recruiting CD3+ T-cells and F4/80+ macrophages. CONCLUSIONS: The results of this study have suggested that this natural, non-toxic compound can be an effective anti-tumor strategy for clinical cancer therapy. mEHT can enable cellular uptake of potential anti-tumor materials and create a favorable tumor microenvironment for an immunological chain reaction that improves the success of combined treatments of curcumin and resveratrol.

Relationship between Energy Dosage and Apoptotic Cell Death by Modulated Electro-Hyperthermia.

Modulated electro-hyperthermia (mEHT) is a form of mild hyperthermia (HT) used for cancer treatment. The principle utility of HT is the ability not only to increase cell temperature, but also to increase blood flow and associated pO2 to the microenvironment. While investigational evidence has shown the unique ability of mEHT to elicit apoptosis in cancer cells, in vivo and in vitro, the same trait has not been observed with conventional HT. There is dissension as to what allows mEHT to elicit apoptosis despite heating to only mild temperatures, with the predominant opinion in favor of increased temperature at a cellular level as the driving force. For this study, we hypothesized that in addition to temperature, the amount of electrical energy delivered is a major factor in induction of apoptosis by mEHT. To evaluate the impact of electrical energy on apoptosis, we divided generally practiced mEHT treatment into 3 phases: Phase I (treatment start to 10 min. mark): escalation from 25 °C to 37 °C Phase II (10 min. mark to 15 min. mark): escalation from 37 °C to 42 °C Phase III (15 min. mark to 45 min. mark): maintenance at 42 °C Combinations of mEHT at 18 W power, mEHT at 7.5 W power, water bath, and incubator were applied to each of the three phases. Power output was recorded per second and calculated as average power per second. Total number of corresponding Joules emitted per each experiment was also recorded. The biological effect of apoptotic cell death was assayed by annexin-V assay. In group where mEHT was applied for all three phases, apoptosis rate was measured at 31.18 ± 1.47%. In group where mEHT was only applied in Phases II and III, apoptosis rate dropped to 20.2 ± 2.1%. Where mEHT was only applied in Phase III, apoptosis was 6.4 ± 1.7%. Interestingly, when mEHT was applied in Phases I and II, whether Phase III was conducted in either water bath at 42 °C or incubator at 37 °C, resulted in nearly identical apoptosis rates, 26 ± 4.4% and 25.9 ± 3.1%, respectively. These results showed that accumulation of mEHT at high-powered setting (18 W/sec) during temperature escalation (Phase I and Phase II), significantly increased apoptosis of tested cancer cells. The data also showed that whereas apoptosis rate was significantly increased during temperature escalation by higher power (18 W/sec), apoptosis was limited during temperature maintenance with lower power (7.5 W/sec). This presents that neither maintenance of 42 °C nor accumulation of Joules by mEHT has immediate correlating effect on apoptosis rate. These findings may offer a basis for direction of clinical application of mEHT treatment.

Treatment of Spinal Tuberculosis of GATA Type III: Primary Posterior Debridement Combined with Osteotomy Parallel to the Endplates for Reconstruction.

To evaluate the curative effect of one-stage posterior debridement and osteotomy parallel to the endplates for reconstruction, deformity correction, and tuberculosis control on treating the spinal tuberculosis of graded GATA III. From July of 2012 to December of 2017, there were 36 cases from the Second Hospital of Shanxi Medical University with thoracic and lumbar tuberculosis graded GATA III, in which we used osteotomy parallel to the endplates and reconstruction for treatment,16 for males and 20 for females. The local Cobb angles of kyphosis of all patients are greater than or equal to 20.The age varied from 28 months to 72 years with an average of 38.8 years. There were 15 cases of thoracic segment, 12 cases of thoracolumbar segment (T11 -L2 ), 9 cases of lumbar segment. Preoperative results of ASIA were 3 cases of grade C,5 cases of grade D and 28 cases of grade E with an average kyphosis Cobb angle of 37.21 ± 3.28. The visual analogue scale(VAS) scores preoperatively were 0-8 points (averaged 5.58 ± 1.66 points). All the patients had paraspinal abscesses. After completing the preoperative examinations and evaluations, the osteotomy parallel to the endplates and reconstruction were executed. We made a statistical analysis of the Cobb angles, visual analogue scale(VAS) scores, erythrocyte sedimentation rate (ESR), C-reaction protein(CRP), and ASIA grades before and after the surgery. The following-up time varied from 12 to 24 months, with an average of 18 months. The VAS score improved from 5.58 ± 1.66 before the surgery to 3.25 ± 0.92 one month after the surgery and 2.12 ± 0.73 at the last follow-up. The Cobb angles decreased from 37.21° ± 3.28° before the surgery to 5.72°± 2.66° one month later and 5.99° ± 1.92° at the last follow-up. The ESR decreased from 55.34 ± 1.72 mm/1 h before the surgery to 28.22 ± 3.76 mm/1 h one month later and 11.54 ± 0.46 mm/1 h at the last follow-up. The CRP decreased from 35.22 ± 2.46 mg/L before to 12.67 ± 2.82 mg/L and 4.50 ± 2.11 mg/L at the last follow-up. The results of the last ASIA grades were 1 case of grade D and 35 cases of grade E. The one-stage posterior debridement and osteotomy parallel to the endplates for patients with spinal tuberculosis of graded GATA III are not only beneficial to spinal reconstruction, but also obtain ideal reconstuction effects.

Putative Abscopal Effect in Three Patients Treated by Combined Radiotherapy and Modulated Electrohyperthermia.

Purpose: True abscopal responses from radiation therapy are extremely rare; the combination of immune checkpoint inhibitors with radiation therapy has led to more reports of the abscopal effect, but even in this setting, the genuine magnitude remains unknown and is still considered generally uncommon. We report the occurrence of what appears to be putative, durable abscopal tumor responses with associated auto-immune systemic reactions resulting from the combination of local radiotherapy (RT) and modulated electrohyperthermia (mEHT). Materials and Methods: Data from advanced cancer patients treated palliatively with RT and mEHT between January and December 2017 were collected as part of a post-marketing safety monitoring program of mEHT therapy. We specified a minimum RT dose of 30 Gy and at least four mEHT treatments for reporting toxicities, which was the primary aim of the larger study. Results: Thirty-three patients treated with RT and mEHT, both applied to the same lesion, were included. The median RT dose was 45.5 Gy in 20 fractions (fxs) and the median number of mEHT treatments was 12 (range, 4-20). Most patients had subsequent systemic therapy after one course of RT and mEHT. Three patients (9.1%) developed autoimmune toxicities. Case number 1 received RT and mEHT only; case number 2 had two cycles of concurrent low dose chemotherapy during RT; and case number 3 received concurrent immune checkpoint inhibitors. None of the three patients received any further systemic treatment due to obvious treatment-related autoimmune reactions which occurred rapidly after RT; one had autoimmune hepatitis, one had dermatitis herpetiformis and the third developed severe myasthenia gravis. Interestingly, what we surmise to be long-lasting abscopal responses outside the irradiated area, were noted in all three patients. Conclusion: RT combined with mEHT could putatively result in enhancing immune responsiveness. These preliminary observational findings lead to the generation of a hypothesis that this combination induces both an in-situ, tumor-specific immune reaction and an anti-self-autoimmune reaction, in at least a small proportion of patients, and of those who experience the auto-immune response, tumor response is a concomitant finding. Mechanisms underlying this phenomenon need to be investigated further.

Neuroprotective effects of resveratrol against oxygen glucose deprivation induced mitochondrial dysfunction by activation of AMPK in SH-SY5Y cells with 3D gelatin scaffold.

Ischemic stroke arising from the sudden blockage of arteries in the brain, is a common and serious brain damaging problem worldwide, often leading to disability or death. The oxygen glucose deprivation (OGD) model was created to improve understanding of hypoxia- and hypoglycemia-induced neuronal cell injury, and provide an in vitro surrogate to assess novel treatments for cerebral hypoxia-ischemia. AMP-activated protein kinase (AMPK) is a critical neuroprotective regulator of energy homeostasis, metabolism and cell survival. However, the neuroprotective mechanisms by which AMPK achieves these beneficial effects in human SH-SY5Y neural cells exposed to OGD are still not well understood. Resveratrol is a potent activator of AMPK suggesting it may have therapeutic potential as a neuroprotective agent. Therefore, we hypothesized the AMPK activator resveratrol protects against OGD-mediated impairment of human SH-SY5Y neuronal cells. The novelty of the experiment using a 3D gelatin scaffold cell culture assay, we have tested the potential of 3D systems to mimic the endogenous neuronal environment and have applied these systems to study the effect of OGD on neuronal cells with/without resveratrol. Here we show resveratrol reverses, via AMPK-dependent downregulation of caspase 3 and 9 activity, the OGD-mediated decreases in SH-SY5Y cell viability on a 3D gelatin scaffold. In addition, treatment with OGD decreases mRNA levels of AMPK and the neuroprotective genes (Bcl-2 and CREB); however, co-treatment with resveratrol significantly normalizes these effects. Importantly, resveratrol improves the expression of AMPK and p-AMPK in OGD-exposed SH-SY5Y cells. Resveratrol also significantly rescues SH-SY5Y cells from OGD-mediated mitochondrial deficiency (lower D-loop level, mitochondrial mass, maximal respiratory function, COX activity, and mitochondrial membrane potential). Resveratrol also rescues the transcript expression levels of PGC1α and mitochondrial genes (NRF-1 and Tfam) in OGD-treated SH-SY5Y cells. These findings extend our mechanistic understanding of the central role of AMPK in OGD-related neuronal impairment, and may serve as basis for implementing new therapeutic strategies in the treatment of ischemic stroke.

Identification of novel cell glycolysis related gene signature predicting survival in patients with endometrial cancer.

BACKGROUND: Endometrial cancer (EC) is one of the three major gynecological malignancies. Numerous biomarkers that may be associated with survival and prognosis have been identified through database mining in previous studies. However, the predictive ability of single-gene biomarkers is not sufficiently specific. Genetic signatures may be an improved option for prediction. This study aimed to explore data from The Cancer Genome Atlas (TCGA) to identify a new genetic signature for predicting the prognosis of EC. METHODS: mRNA expression profiling was performed in a group of patients with EC (n = 548) from TCGA. Gene set enrichment analysis was performed to identify gene sets that were significantly different between EC tissues and normal tissues. Cox proportional hazards regression models were used to identify genes significantly associated with overall survival. Quantitative real-time-PCR was used to verify the reliability of the expression of selected mRNAs. Subsequent multivariate Cox regression analysis was used to establish a prognostic risk parameter formula. Kaplan-Meier survival estimates and the log-rank test were used to validate the significance of risk parameters for prognosis prediction. RESULT: Nine genes associated with glycolysis (CLDN9, B4GALT1, GMPPB, B4GALT4, AK4, CHST6, PC, GPC1, and SRD5A3) were found to be significantly related to overall survival. The results of mRNA expression analysis by PCR were consistent with those of bioinformatics analysis. Based on the nine-gene signature, the 548 patients with EC were divided into high/low-risk subgroups. The prognostic ability of the nine-gene signature was not affected by other factors. CONCLUSION: A nine-gene signature associated with cellular glycolysis for predicting the survival of patients with EC was developed. The findings provide insight into the mechanisms of cellular glycolysis and identification of patients with poor prognosis in EC.

NF-κB-mediated inflammatory damage is differentially affected in SH-SY5Y and C6 cells treated with 27-hydroxycholesterol.

Previous studies have demonstrated that 27-hydroxycholesterol (27-OHC), a cholesterol metabolite, was involved in the inflammatory process of Alzheimer's disease (AD). The present study aimed to investigate the 27-OHC-induced inflammatory damage to neurons and astrocytes and the underlying mechanism(s) accounting for this damage. Human neuroblastoma cells (SH-SY5Y cells) and rat glioma cells (C6 cells) were treated with vehicle or 27-OHC (5, 10, or 20 µM) for 24 hr. The levels of secreted interleukin-1ß (IL-1ß), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), and inducible nitric oxide synthase (iNOS) were determined by using an enzyme-linked immunosorbent assay (ELISA). Immunofluorescence staining was used to determine the cellular expression of toll-like receptor 4 (TLR4) and transforming growth factor-ß (TGF-ß). The mRNA and protein expression levels of nuclear factor-κB p65 (NF-κB p65), nuclear factor-κB p50 (NF-κB p50) and cyclooxygenase-2 (COX-2) in both SH-SY5Y and C6 cells were also detected by real-time PCR and Western blot, respectively. The results of this study showed that 27-OHC treatment increased secretion of TNF-α and iNOS and decreased secretion of IL-10, upregulated expression of TGF-ß, NF-κB p65 and p50, and downregulated expression of COX-2 in SH-SY5Y cells. In C6 cells, treatment with 27-OHC resulted in decreased secretion of IL-1ß, IL-10, TNF-α, and iNOS, and increased expression of TLR4 and TGF-ß. These results suggest that 27-OHC may cause inflammatory damage to neurons by activating the TGF-ß/NF-κB signaling pathway and to astrocytes by activating the TLR4/TGF-ß signaling, which results in the subsequent release of inflammatory cytokines.