Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced in vitro and in vivo model.

Numerous studies have shown that neuroinflammation is involved in the process of neuronal damage in neurodegenerative diseases such as Parkinson's disease (PD), for example, and that inhibiting neuroinflammation help improve PD. Shikimic acid (SA) has anti-inflammatory, analgesic and antioxidant activities in numerous diseases. However, its effect and mechanism in PD remain unclear. In this experiment, we found that SA inhibits production of pro-inflammatory mediators and ROS in LPS-induced BV2 cells. Mechanistic studies demonstrated that SA suppresses neuro-inflammation by activating the AKT/Nrf2 pathway and inhibiting the NF-κB pathway. Further in vivo study, we confirmed that SA ameliorated the neurological damage and behavioral deficits caused by LPS injection in mice. In summary, these study highlighted the beneficial role of SA as a novel therapy with potential PD drug by targeting neuro-inflammation.

Mechanisms and applications of radiation-induced oxidative stress in regulating cancer immunotherapy.

Radiotherapy (RT) is an effective treatment option for cancer patients, which induces the production of reactive oxygen species (ROS) and causes oxidative stress (OS), leading to the death of tumor cells. OS not only causes apoptosis, autophagy and ferroptosis, but also affects tumor immune response. The combination of RT and immunotherapy has revolutionized the management of various cancers. In this process, OS caused by ROS plays a critical role. Specifically, RT-induced ROS can promote the release of tumor-associated antigens (TAAs), regulate the infiltration and differentiation of immune cells, manipulate the expression of immune checkpoints, and change the tumor immune microenvironment (TME). In this review, we briefly summarize several ways in which IR induces tumor cell death and discuss the interrelationship between RT-induced OS and antitumor immunity, with a focus on the interaction of ferroptosis with immunogenic death. We also summarize the potential mechanisms by which ROS regulates immune checkpoint expression, immune cells activity, and differentiation. In addition, we conclude the therapeutic opportunity improving radiotherapy in combination with immunotherapy by regulating OS, which may be beneficial for clinical treatment.

d-lactate modulates M2 tumor-associated macrophages and remodels immunosuppressive tumor microenvironment for hepatocellular carcinoma.

The polarization of tumor-associated macrophages (TAMs) from M2 to M1 phenotype demonstrates great potential for remodeling the immunosuppressive tumor microenvironment (TME) of hepatocellular carcinoma (HCC). d-lactate (DL; a gut microbiome metabolite) acts as an endogenous immunomodulatory agent that enhances Kupffer cells for clearance of pathogens. In this study, the potential of DL for transformation of M2 TAMs to M1 was confirmed, and the mechanisms underlying such polarization were mainly due to the modulation of phosphatidylinositol 3-kinase/protein kinase B pathway. A poly(lactide-co-glycolide) nanoparticle (NP) was used to load DL, and the DL-loaded NP was modified with HCC membrane and M2 macrophage-binding peptide (M2pep), forming a nanoformulation (DL@NP-M-M2pep). DL@NP-M-M2pep transformed M2 TAMs to M1 and remodeled the immunosuppressive TME in HCC mice, promoting the efficacy of anti-CD47 antibody for long-term animal survival. These findings reveal a potential TAM modulatory function of DL and provide a combinatorial strategy for HCC immunotherapy.

Advances in electrical impedance tomography-based brain imaging.

Novel advances in the field of brain imaging have enabled the unprecedented clinical application of various imaging modalities to facilitate disease diagnosis and treatment. Electrical impedance tomography (EIT) is a functional imaging technique that measures the transfer impedances between electrodes on the body surface to estimate the spatial distribution of electrical properties of tissues. EIT offers many advantages over other neuroimaging technologies, which has led to its potential clinical use. This qualitative review provides an overview of the basic principles, algorithms, and system composition of EIT. Recent advances in the field of EIT are discussed in the context of epilepsy, stroke, brain injuries and edema, and other brain diseases. Further, we summarize factors limiting the development of brain EIT and highlight prospects for the field. In epilepsy imaging, there have been advances in EIT imaging depth, from cortical to subcortical regions. In stroke research, a bedside EIT stroke monitoring system has been developed for clinical practice, and data support the role of EIT in multi-modal imaging for diagnosing stroke. Additionally, EIT has been applied to monitor the changes in brain water content associated with cerebral edema, enabling the early identification of brain edema and the evaluation of mannitol dehydration. However, anatomically realistic geometry, inhomogeneity, cranium completeness, anisotropy and skull type, etc., must be considered to improve the accuracy of EIT modeling. Thus, the further establishment of EIT as a mature and routine diagnostic technique will necessitate the accumulation of more supporting evidence.

Mechanism and Protection of Radiotherapy Induced Sensorineural Hearing Loss for Head and Neck Cancer.

PURPOSE: Radiotherapy-induced sensorineural hearing loss (RISNHL) is a common adverse effect in patients with head and neck cancer. Given that there are few studies on the pathogenesis of RISNHL at present, we summarized the possible pathogenesis of RISNHL and possible protective measures found at present by referring to relevant literatures. METHODS: We performed a comprehensive literature search in the PubMed database, using keywords "sensorineural hearing loss," "radiotherapy," and "cancer," among others. The literature was examined for the possible mechanism and preventive measures of sensorineural hearing loss induced by radiotherapy. RESULTS: We found that the incidence of RISNHL was closely related to the damage directly caused by ionizing radiation and the radiation-induced bystander effect. It also depends on the dose of radiation and the timing of chemotherapy. Studies confirmed that RISNHL is mainly involved in post-RT inflammatory response and changes in reactive oxygen species, mitogen-activated protein kinase, and p53 signaling pathways, leading to specific manners of cell death. We expect to reduce the incidence of hearing loss through advanced radiotherapy techniques, dose limitation of organs at risk, application of cell signaling inhibitors, use of antioxidants, induction of cochlear hair cell regeneration, and cochlear implantation. CONCLUSION: RISNHL is associated with radiation damage to DNA, oxidative stress, and inflammation of cochlear cells, stria vascularis endothelial cells, vascular endothelial cells, spiral ganglion neurons, and other supporting cells. At present, the occurrence mechanism of RISNHL has not been clearly illustrated, and further studies are needed to better understand the underlying mechanism, which is crucial to promote the formulation of better strategies and prevent the occurrence of RISNHL.

[Establishment and Application of Performance Evaluation and Obstacle Diagnosis Model for Regional Water Ecological Civilization Construction].

A scientific performance evaluation of the regional water ecological civilization construction and clarifying the obstacle factor are key points to improve the performance of regional water ecological civilization construction theory. This study analyzes the coupling relationship between humans and regional water ecology by applying the thinking logic of "driving force-pressure-state-influence-response-management." The regional water ecological civilization construction performance evaluation index system based on the DPSIRM model was established. Combining the unascertained measurement model and obstacle diagnosis model, the water ecological civilization construction performance of Shizuishan City during the past 10 years was empirically evaluated, and the obstacle factors affecting local construction performance were diagnosed and analyzed. The analytical results reveal the following points:First, the performance of the water ecological civilization construction in Shizuishan City gradually increased annually and revealed three development stages:the site visit and slow improvement (2010-2014), intermediate but fast improvement (2015-2017) and good and fast improvement (2018-2019). Second, each subsystem performance index trend varied, but generally, the fluctuations rose. Third, from 2010 to 2014, the average obstacle degree of the subsystem state, subsystem response, and subsystem pressure reached 58.81%, which became the main obstacles restricting the performance of the local water ecological civilization construction. From 2015 to 2017, the average pressure barrier degree reached 21.73%, which was the most significant obstacle to the construction performance. From 2018 to 2019, the average pressure barrier degree remained the largest obstacle by reaching 24.49%. Lastly, the index barrier of the obstacle degree among the top five factors are primarily distributed in the pressure subsystem. A comprehensive frequency ranking of the obstacles, the irrigation water use coefficient, and the pressure of the water consumption per ten thousand yuan of value-added by industry as a representative subsystem are the key directions to future construction. In this paper, the concepts and methods of the research can provide a theoretical reference for the performance evaluation of regional water ecological civilization construction and its obstacle factor diagnosis analysis.

Graphene Oxide Composite for Selective Recognition, Capturing, Photothermal Killing of Bacteria over Mammalian Cells.

The multifunctional photothermal therapy (PTT) platform with the ability to selectively kill bacteria over mammalian cells has received widespread attention recently. Herein, we prepared graphene oxide-amino(polyethyleneglycol) (GO-PEG-NH2) while using the hydrophobic interaction between heptadecyl end groups of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethyleneglycol)] (DSPE-PEG-NH2) and graphene oxide (GO). Based on GO-PEG-NH2, the versatile PTT system was constructed with simultaneous selective recognition, capturing, and photothermal killing of bacteria. When the cells undergo bacterial infection, owing to the poly(ethylene glycol) (PEG) chains and positively charged amino groups, GO-PEG-NH2 can specifically recognize and capture bacteria in the presence of cells. Meanwhile, the stable photothermal performance of GO-PEG-NH2 enables the captured bacteria to be efficiently photothermally ablated upon the irradiation of 808 nm laser. Besides, the GO-PEG-NH2 is highly stable in various biological media and it exhibits low cytotoxicity, suggesting that it holds great promise for biological applications. This work provides new insight into graphene-based materials as a PTT agent for the development of new therapeutic platforms.

Synergistic Photodynamic and Photothermal Antibacterial Therapy Based on a Conjugated Polymer Nanoparticle-Doped Hydrogel.

Herein, we have developed a composite antibacterial hydrogel with photodynamic therapy (PDT) and photothermal therapy (PTT) antibacterial capabilities, triggered by white light and NIR light irradiation. A water-insoluble conjugated polymer (PDPP) with photothermal ability was prepared into nanoparticles by the nanoprecipitation method, and the cell-penetrating peptide TAT was grafted on the surface of the nanoparticles. Based on our previous work that developed a hybrid hydrogel with an enhanced PDT effect from polyisocyanide (PIC) hydrogel and cationic conjugated polythiophene (PMNT), PDPP nanoparticles (CPNs-TAT) with photothermal ability are introduced to realize the synergistic antibacterial effect of PDT and PTT. Using the PIC hydrogel to combine PIC and CPNs-TAT has the following advantages. First, the PIC hydrogel can regulate the aggregation state of PMNT, making it better dispersed and improving its capacity of reactive oxygen species (ROS) production. Second, CPNs-TAT can be uniformly dispersed in the PIC hybrid, thereby avoiding the toxicity caused by too high local concentration, achieving a uniform increase in system temperature, and enhancing the therapeutic effect of PTT. Third, the PIC hybrid has the synergistic treatment effect of PDT and PTT. The PIC hybrid intelligently regulates its antibacterial ability through white light and NIR light, which can be used in the white light and NIR light areas. When irradiated with white light and NIR light sequentially, synergistic PDT and PTT exhibit stronger antibacterial ability than PDT or PTT alone. The combination of two antibacterial methods realizes the dual-control antibacterial hydrogel of PDT and PTT and provides an antibacterial mode based on PIC hybrids. Therefore, the PIC hybrids are promising as an antibacterial excipient for clinical wounds.

Effects of dance intervention on global cognition, executive function and memory of older adults: a meta-analysis and systematic review.

OBJECTIVE: To summarize and assess the effects of dance intervention on global cognition, executive function and memory in older adults. METHODS: We searched the databases PubMed, Web of Science, Cochrane Library, EMBASE, Clinical Trials.Gov and four Chinese databases (CNKI, CBM, Wan Fang Data and VIP) to identify articles written in English or Chinese and published until April 2018. Randomized controlled trials and quasi-experiment were included if they evaluated the impact of dance on cognition, and individuals aged 60 and over. RESULTS: Thirteen studies with a total of 1605 participants met the inclusions criteria. Our primary outcomes of interest are cognitive functions and are categorized into three cognitive domains: (1)Global cognition: meta-analyses for outcome related to global cognition indicated a large effect size. In the subgroup of using MMSE, results indicated a significant effect for dance on cognition [MD = 1.57, 95% CI (0.53, 2.61), p = 0.003; I2 = 62%], in the subgroup of using SCEF, effect sizes was statically significant and no heterogeneity between studies [MD = 33.25, 95% CI (30.94, 35.56), p < 0.00001; I2 = 0%]. (2)Executive functioning domain: meta-analyses revealed that there were no significant differences between the two groups in measures of executive function after the one study with a low-quality score was excluded [SMD = 0.13, 95% CI (- 0.02, 0.27), p = 0.09; I2 = 0%]. (3)Memory domain: quantitative analysis showed that dance may benefit memory function in older adults. However, in our review, dance was more effective for elderly cognitions than exercise may be not support. CONCLUSIONS: Our meta-analysis and systematic review suggest that dance may be a safe and effective approach to improve cognitive function in older adults.

Giant malignant phyllodes tumor of the breast: A rare case report and literature review.

Malignant phyllodes tumor of the breast (MPTB) is rarely encountered in clinical practice. Preoperative diagnosis is challenging due to nonspecific radiological and histological features, and the prognostic factors and optimal treatment remain controversial. The current report describes the case of a middle-aged female with giant MPTB who underwent multidisciplinary intervention, including surgery, postoperative chemotherapy and radiotherapy. To date, the disease-free survival (DFS) of the patient has reached 18 months. Furthermore, a related literature review summarize the clinicopathological characteristics and treatment progress regarding MPTB is presented, along with an analysis of the indications for therapeutic strategy in the current case. In the future, multi-center clinical trials must be initiated to identify the criteria for diagnosis and optimal treatment consensus for MPTB. In conclusion, the present case highlights that multidisciplinary management may contribute to DFS following the treatment of giant MPTB.

Alteration of 11ß-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor by ethanol in rat liver and mouse hepatoma cells.

Alcohol is a potential risk factor of type 2 diabetes, but its underlying mechanism is unclear. To explore this issue, Wistar rats and mouse hepatoma cells (Hepa 1-6) were exposed to ethanol, 8 g·kg(-1) ·d(-1) for 3 months and 100 mM for 48 h, respectively. Glucose and insulin tolerance tests in vivo were performed, and protein levels of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) and glucocorticoid receptor (GR) in liver and Hepa 1-6 cells were measured. Alterations of key enzymes of gluconeogenesis phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6 phosphatase (G6Pase), as well as glycogen synthase kinase 3a (GSK3 α ), were also examined. The results revealed that glucose levels were increased, and insulin sensitivity was impaired accompanied with liver injury in rats exposed to ethanol compared with controls. The 11ß-HSD1, GR, PEPCK, G6Pase, and GSK3 α proteins were increased in the liver of rats treated with ethanol compared with controls. Ethanol-exposed Hepa 1-6 cells also showed higher expression of 11ß-HSD1, GR, PEPCK, G6Pase, and GSK3 α proteins than control cells. After treatment of Hepa 1-6 cells exposed to ethanol with the GR inhibitor RU486, the expression of 11ß-HSD1 and GR was significantly decreased. At the same time the increases in PEPCK, G6Pase, and GSK3 α levels induced by ethanol in Hepa 1-6 cells were also attenuated by RU486. The results indicate that ethanol causes glucose intolerance by increasing hepatic expression of 11ß-HSD1 and GR, which leads to increased expression of gluconeogenic and glycogenolytic enzymes.