Advantages of nanocarriers for basic research in the field of traumatic brain injury

A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.

3D-printed engineered bacteria-laden gelatin/sodium alginate composite hydrogels for biological detection of ionizing radiation

Nuclear safety is a global growing concern,where ionizing radiation(IR)is a major injury factor resulting in serious damage to organisms.The detection of IR is usually conducted with physical dosimeters;however,biological IR detection methods are deficient.Here,a living composite hydrogel consisting of engineered bacteria and gelatin/sodium alginate was 3D-printed for the biological detection of IR.Three strains of PrecA::egfp gene circuit-containing engineered Escherichia coli were constructed with IR-dependent fluorescence,and the DH5αstrain was finally selected due to its highest radiation response and fluorescence.Engineered bacteria were loaded in a series of gelatin/sodium alginate matrix hydrogels with different rheology,3D printability and bacterial applicability.A high-gelatin-content hydrogel containing 10%gelatin/1.25%sodium alginatewas optimal.The optimal living composite hydrogelwas 3D-printedwith the special bioink,which reported significant green fluorescence underγ-ray radiation.The living composite hydrogel provides a biological strategy for the detection of environmental ionizing radiation.

Synaptic Transmission of Primary Hippocampal Neurons was Enhanced after Terahertz Waves Exposure

Terahertz(THz)waves,also known as T-rays,encompass frequencies ranging from 0.1 to 10 THz and possess unique properties that render them applicable in various biomedical domains,particularly in neurobiology[1].Synaptic transmission,the process through which signals propagate between neurons at synapses,is pivotal for brain function and information processing.

Hepatocyte growth factor enhances the ability of dental pulp stem cells to ameliorate atherosclerosis in apolipoprotein E-knockout mice

BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.

Ferulic acid reduces inflammatory response induced by radiation through Sirt1-NLRP3 pathway

Objective:A model of inflammatory damage was induced by radiation to investigate whether ferulic acid(FA)can reduce the inflammatory response through the Sirt1-NLRP3 inflammatory pathway.This will help discover radiation-protective drugs and elucidate the molecular mechanisms related to radiation-induced inflammatory damage.Methods:A mouse model of radiation-induced immunoinflammatory injury was established to verify the anti-inflammatory effects of FA in vivo.C57BL/6J mice were randomly divided into six groups,and 5 Gy whole-body irradiation was used for modeling.Mice were administered a gastric solvent,amifostine,or 25,50,or 100 mg/kg FA daily for 12 days,consecutively,before irradiation.The serum of mice was collected 24 hour after irradiation to observe the content of inflammatory factors interleukin(IL)-1β,IL-18,IL-6,and tumor necrosis factor(TNF)-α.The spleen and thymus tissues of mice were weighed and the organ index was calculated for pathological testing and immunofluorescence detection.Results:FA reduced the radiation-induced decrease in the spleen and thymus indices.FA significantly reduced the secretion of inflammatory factors in the serum and reversed the radiation-induced reduction in lymphocytes in the spleen and thymus of mice.FA activated Sirt1 and inhibited the expression of the NLRP3 inflammasome to alleviate the inflammatory response.Conclusions:FA reduced radiation-induced inflammation in animals,possibly by activating Sirt1 and reducing nucleotide oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome expression,thereby reducing the secretion of inflammatory factors.

Effects of Electromagnetic Radiation on Autophagy and its Regulation

With the ever increasing application of electronic technology, our exposure to artificial electromagnetic energy is also rapidly increasing. Electromagnetic radiation （EMR） is the fourth largest source of pollution, after air, water, and noise.

Advances in the biological effects of terahertz wave radiation

The terahertz(THz) band lies between microwave and infrared rays in wavelength and consists of non-ionizing radiation. Both domestic and foreign research institutions, including the army, have attached considerable importance to the research and development of THz technology because this radiation exhibits both photon-like and electron-like properties, which grant it considerable application value and potential. With the rapid development of THz technology and related applications, studies of the biological effects of THz radiation have become a major focus in the field of life sciences. Research in this field has only just begun, both at home and abroad. In this paper, research progress with respect to THz radiation, including its biological effects, mechanisms and methods of protection, will be reviewed.

Biological effects and mechanisms of shortwave radiation： a review

With the increasing knowledge of shortwave radiation,it is widely used in wireless communications,radar observations,industrial manufacturing,and medical treatments.Despite of the benefits from shortwave,these wide applications expose humans to the risk of shortwave electromagnetic radiation,which is alleged to cause potential damage to biological systems.This review focused on the exposure to shortwave electromagnetic radiation,considering in vitro,in vivo and epidemiological results that have provided insight into the biological effects and mechanisms of shortwave.Additionally,some protective measures and suggestions are discussed here in the hope of obtaining more benefits from shortwave with fewer health risks.

Inhibition of Micro RNA 219 Expression Protects Synaptic Plasticity via Activating NMDAR1, Ca MKIIγ,and p-CREB after Microwave Radiation

In recent decades,the potential health hazards of microwave exposure have been attracting increasing attention.Our previous studies have demonstrated that microwave exposure impaired learning and memory in experimental animal models[1,2].

Recent advances in the effects of microwave radiation on brains

This study concerns the effects of microwave on health because they pervade diverse fields of our lives. The brain has been recognized as one of the organs that is most vulnerable to microwave radiation. Therefore, in this article, we reviewed recent studies that have explored the effects of microwave radiation on the brain, especially the hippocampus, including analyses of epidemiology, morphology, electroencephalograms, learning and memory abilities and the mechanisms underlying brain dysfunction. However, the problem with these studies is that different parameters, such as the frequency, modulation, and power density of the radiation and the irradiation time, were used to evaluate microwave radiation between studies. As a result, the existing data exhibit poor reproducibility and comparability. To determine the specific dose-effect relationship between microwave radiation and its biological effects, more intensive studies must be performed.

Establishment of injury models in studies of biological effects induced by microwave radiation

Microwave radiation has been widely used in various fields,such as communication,industry,medical treatment,and military applications.Microwave radiation may cause injuries to both the structures and functions of various organs,such as the brain,heart,reproductive organs,and endocrine organs,which endanger human health.Therefore,it is both theoretically and clinically important to conduct studies on the biological effects induced by microwave radiation.The successful establishment of injury models is of great importance to the reliability and reproducibility of these studies.In this article,we review the microwave exposure conditions,subjects used to establish injury models,the methods used for the assessment of the injuries,and the indicators implemented to evaluate the success of injury model establishment in studies on biological effects induced by microwave radiation.

Monte Carlo simulation for performance evaluation of detector model with a monolithic LaBr_(3)(Ce)crystal and SiPM array forγradiation imaging

In recent years,LaBr_(3)(Ce)crystals and silicon photomultipliers(SiPMs)have been increasingly used in radiation imaging.This study involved the establishment of a detector model with a monolithic LaBr_(3)(Ce)crystal and SiPM array forγ-radiation imaging on the GEANT4 platform.The optical process included in the detector model was defined by key parameters,such as the emission spectrum,scintillation yield,and intrinsic resolution of the LaBr_(3):5%Ce crystal,as well as the detection efficiency of the SiPM array.The response of the detector model to^(57)Co flooded field irradiation was simulated and evaluated.The radiation images generated by the detector model exhibited a compression effect that was very close to that on images acquired by the physical detector.The spatial resolution of the simulated detector closely approximates that of the physical experiment.A detector model without the optical process was also established for comparison with a detector using the optical process.Both were used in a near-field modified uniform redundant array(MURA)imaging system to acquire images of a point source and a ring source of^(57)Co at the center of the field-of-view of the imaging system.The spatial resolution and signal-to-noise ratio of the images that were reconstructed using the two detector models were determined and compared.Compared with the detector model without optical processes,although the images from the proposed detector model have slightly inferior signal-to-noise ratios and more artifacts,they are more consistent with the reconstructed versions of images acquired in real physical experiments.The results confirm that the detector model can be used to design aγ-radiation imaging detector and to develop an imaging algorithm that can significantly shorten the development time and reduce the cost.

Effects of microwave radiation on brain energy metabolism and related mechanisms

With the rapid development of electronic technologies, anxiety regarding the potential health hazards induced by microwave radiation(MW) has been growing in recent years. The brain is one of the most sensitive target organs for microwave radiation, where mitochondrial injury occurs earlier and more severely than in other organs. Energy metabolism disorders do play an important role during the process of microwave radiation-induced brain damage. In this paper, we will review the biological effects of microwave radiation, the features of brain energy supply and consumption and the effects of microwave radiation on mitochondrial energy metabolism and potential related mechanisms.

Lycium barbarum polysaccharide ameliorates radiation-induced brain injury by regulating gut microbiota

Objective: To determine the extent to which Lycium barbarum polysaccharide(LBP) improves60Co γ-ray radiation-induced brain injury(RIBI) by regulating the gut microbiota.Methods: The RIBI model of mice was established with the appropriate dose of60Co γ-ray to identify the changes in the body weight, behaviors, gut microbiota, and inflammatory reactions of mice. Mice were randomly divided into healthy, RIBI model, and LBP groups. The related inflammatory cytokines were determined using an enzyme linked immunosorbent assay kit. Then, 16S rRNA sequencings of feces were carried out to evaluate the differences in intestinal flora.Results: Compared with the spontaneous activity and exploratory spirit of the healthy group, those traits in the RIBI model mice in the open field significantly decreased, the freezing time in the elevated plus maze(EPM) significantly increased, and the number of times the mice discriminated the novel object was significantly lower. Hematoxylin-eosin slides showed that the main histopathological changes of RIBI occurred in the hippocampus. In addition, the diversity and relative abundances ratio of the gut bacterial phylum, order, family, and genus in the model group varied widely. Changes in Bacteroidetes,Firmicutes, and Proteobacteria were the most obvious after head radiation exposure. In comparison, LBP could accelerate the recovery of weight loss in RIBI mice. The frequency that mice entered the center of the open field, facing the open arm in the EPM, and the number of times they discriminated the novel object were significantly increased with LBP administration. LBP could also reduce the levels of inflammatory factor caused by RIBI. LBP increased the diversity and abundance of gut microbiota in RIBI model mice. In addition, LBP increased the relative abundance of Bacteroidetes but decreased the levels of Firmicutes and Proteobacteria for irradiated mice.Conclusion: LBP can improve depression and tension by regulating the composition of gut microbiota,including lowering the relative abundance of Clostridia and Burkholderiales and raising that of Lactobacillales. Thus, LBP provides a new strategy for improving the protective effects of RIBI.

Differential expression of telomerase reverse transcriptase in chronic human skin ulcer induced by radiation and mechanism of cancer transformation and poor healing

AIM:To study the expression of the catalytic subunit of telomerase, telomerase reverse transcriptase(TRT) and explore the possible relationship between the TR T and cancer transformation or poor healing in radiation-induced chronic human skin ulcer.METHODS:Rabbit antibody to human TRT and SP immunohistochemical metho d were used to detect TRT expression in 24 cases of formalin-fixed,paraffin-em beded chronic human skin ulcer tissues induced by radiation, 5 cases of normal s kin,2 of burnt skin,and 8 of carcinoma.RESULTS: The TRT was detected positive in 14 of 24 (58.3%) chronic radiation ulcers, of which the strongly positive was 10 of 24 (41.7%) and the weakly positive 4 of 24 (16.7%);in 0 of 5 normal and 0 of 2 burnt skins;and in 8 of 8 (100%) carcinomas.The expression of TRT was ob served almost always strongly positive in the cytoplasm and nucleus of squamous epithelial cells of epidermis but negatively in the endoepithelial cells of capi llaries and small blood vessels,or weakly in the cytoplasm of smooth myocytes of media and fibroblasts,of dermis. Chronic inflammtory cells,such as plasma cells and lymphocytes also showed weakly positive for TRT.CONCLUSION:The strong TRT e xpression in the epidermis could be involved in the cancer transformation from c hronic radiation ulcer to squamous carcinoma, whereas the negative or weak TRT e xpression in the capillaries, small blood vessels and fibroblasts of dermis migh t be responsible for the poor healing of chronic ulcers induced by radiation, ca used by sclerosis of small blood vessels and lack of granulation tissue consisti ng of capillaries and fibroblasts.

Accumulative effects of microwave radiation on cardiac injury in rats

According to the current researches,we could say microwave radiation can cause heart damage.Autophagy plays an important role in the process of heart disease and injury,however,the effects induced by microwave radiation of different frequencies in a rat's heart are still unclear,which are dose-dependent,frequency-dependent and accumulative.So the answer of autophagy influencing myocardial injury induced by microwave remains uncertainty.In our research,we adopted three methods of microwave to observe the results:different power density microwave with the same frequency,different frequency microwave with the same power density and the accumulative effects of two frequency microwaves with the same power density.Based on the experimental result,abnormal electrocardiograms and serum myocardial enzymes were found in the 10 m W/cm^(2)single frequency microwave groups and accumulative groups.

Tanshinone IIA protects intestinal epithelial cells from ferroptosis through the upregulation of GPX4 and SLC7A11

Background:Inflammatory bowel disease(IBD)is a chronic inflammatory disease of the gastrointestinal tract.The destruction of the intestinal epithelial barrier is one of the major pathological processes in IBD pathology.Growing evidence indicated that epithelial cell ferroptosis is linked to IBD and is considered a target process.Methods:RAS-selective lethal 3(RSL3)was used to induce ferroptosis in intestinal epithelial cell line No.6(IEC-6)cells,and cell ferroptosis and the effects of tanshinone IIA(Tan IIA)were determined by cell counting kit-8(CCK-8),reactive oxygen species(ROS)staining,Giemsa staining and transmission electron microscope(TEM).The cell viability of natural product library compounds was determined by CCK-8.The expression of ferroptosis-related genes were detected by real-time quantitative polymerase chain reaction(RT-qPCR)and western blot.Results:Treatment of IEC-6 cells results in the accumulation of ROS and typical morphological characteristics of ferroptosis.RSL3 treatment caused rapid cellular cytotoxicity which could be reversed by ferrostatin-1(Fer-1)in IEC-6 cells.Natural product library screening revealed that Tan IIA is a potent inhibitor of IEC-6 cell ferroptosis.Tan IIA could significantly protect the RSL3-induced ferroptosis of IEC-6 cells.Furthermore,the ferroptosis suppressors,glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and miR-17-92 were found to be early response genes in RSL3-treated cells.Treatment of IEC-6 cells with Tan IIA resulted in upregulation of GPX4,SLC7A11,and miR-17-92.Conclusion:Our study demonstrated that Tan IIA protects IEC-6 cells from ferroptosis through the upregulation of GPX4,SLC7A11,and miR-17-92.The findings might provide a theoretical grounding for the future application of Tan IIA to treat or prevent IBD.

Influence of hypoxia on retinal progenitor and ganglion cells in human induced pluripotent stem cell-derived retinal organoids

AIM:To observe the effect of low oxygen concentration on the neural retina in human induced pluripotent stem cell(hiPSC)-derived retinal organoids(ROs).METHODS:The hiPSC and a three-dimensional culture method were used for the experiments.Generated embryoid bodies(EBs)were randomly and equally divided into hypoxic and normoxic groups.Photographs of the EBs were taken on days 38,45,and 52,and the corresponding volume of EBs was calculated.Simultaneously,samples were collected at these three timepoints,followed by fixation,sectioning,and immunofluorescence.RESULTS:The proportion of Ki67-positive proliferating cells increased steadily on day 38;this proliferationpromoting effect tended to increase tissue density rather than tissue volume.On days 45 and 52,the two groups had relatively similar ratios of Ki67-positive cells.Further immunofluorescence analysis showed that the ratio of SOX2-positive cells significantly increased within the neural retina on day 52(P<0.05).In contrast,the percentage of PAX6-and CHX10-positive cells significantly decreased following hypoxia treatment at all three timepoints(P<0.01),except for CHX10 at day 45(P>0.05).Moreover,the proportion of PAX6-/TUJ1+cells within the neural retinas increased considerably(P<0.01,<0.05,<0.05 respectively).CONCLUSION:Low oxygen promotes stemness and proliferation of neural retinas,suggesting that hypoxic conditions can enlarge the retinal progenitor cell pool in hiPSC-derived ROs.

Enhancing long-term stability of bio-photoelectrochemical cell by defect engineering of a WO_(3-x) photoanode

Bio-photoelectrochemical cells(BPECs)can further expand the use of conventional biofuel cells for renewable energy,but the poor stability of the photoelectrode still hinders their practical application.Herein,a BPEC capable of long-term operating in a fuel-free model is fabricated by WO3-xphotoanode with oxygen vacancy(Ov)and bilirubin oxidase catalyzed biocathode.The construction of Ov on the WO3surface significantly suppresses the dissolution of W species into the electrolyte,and improves the charge separation efficiency and the reaction kinetics during the photoelectrochemical oxygen evolution process,thus enhancing the stability and power output performance of the BPEC.As a result,the assembled BPEC can output an open circuit voltage of 0.81 V and deliver a maximum output power of up to 283μW cm^(-2).Impressively,the BPECs maintain 97%of their original power after 36000 s of consecutive discharge under an enclosed environment.This fuel-free BPEC based on a robust WO3-xphotoanode shows excellent promise for accurate application.

Targeting the organelle for radiosensitization in cancer radiotherapy

Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.