Biphasic photobiomodulation of inflammation in mouse models of common wounds, infected wounds, and diabetic wounds.

Bidirectional photobiomodulation (PBM) therapy is an active research area. However, most studies have focused on its dependence on optical parameters rather than on its tissue-dependent effects. We constructed mouse models of wounds in three inflammatory states (normal, low, and high levels of inflammations) to assess the bidirectional regulatory effect of PBM on inflammation. Mice were divided into three groups to prepare common wounds, diabetic wounds, and bacteria-infected wounds. The same PBM protocol was used to regularly irradiate the wounds over a 14 d period. PBM promoted healing of all three kinds of wounds, but the inflammatory manifestations in each were significantly different. In common wounds, PBM slightly increased the aggregation of inflammatory cells and expression of IL-6 but had no effect on the inflammatory score. For wounds in a high level of inflammation caused by infection, PBM significantly increased TNF-α expression in the first 3 d of treatment but quickly eliminated inflammation after the acute phase. For the diabetic wounds in a low level of inflammation, PBM intervention significantly increased inflammation scores and prevented neutrophils from falling below baseline levels at the end of the 14 d observation period. Under fixed optical conditions, PBM has a bidirectional (pro- or anti-inflammatory) effect on inflammation, depending on the immune state of the target organism and the presence of inflammatory stimulants. Our results provide a basis for the formulation of clinical guidelines for PBM application.

Airborne Nanoplastics Exposure Inducing Irreversible Glucose Increase and Complete Hepatic Insulin Resistance.

As an emerging type of pollutant, microplastics have become a global environmental problem. Approximately, a fifth of the global burden of type 2 diabetes can be attributed to air particulate pollution. However, scientific knowledge remains limited about the effects of airborne nanoplastics (NPs) exposure on metabolic diseases. In this experiment, a whole-body exposure system was used to simulate the real atmospheric environment, and three exposure concentrations combined with the actual environmental concentration were selected to explore the effects of airborne NPs on metabolic diseases. Based on histological analyses, metabolic studies, gene expression, metabolites, and molecular signaling analyses, mice exposed to airborne NPs were observed to show a phenotype of systemic inflammation and complete insulin resistance featuring excessive drinking and eating, weight loss, elevated blood glucose, and decreased triglyceride levels. After airborne NPs exposure, mice were intolerant to glucose and tolerant to insulin. In addition, airborne NPs exposure could result in long-term irreversible hyperglycemia. Together, the research findings provide a strong basis for understanding the hazards of airborne nanopollution on metabolic disorders.

Toxic effects and mechanisms of nanoplastics on embryonic brain development using brain organoids model.

Nanoplastics can be easily absorbed into the human body through inhalation, ingestion, and skin contact due to their physicochemical property. Despite the numerous studies postulating the potential adverse effects of environmental exposure to nanoplastics on neurodevelopment, the effects of nanoplastics and their regulatory mechanisms have not been specifically elucidated. We focused on the toxic effects of nanoplastics on brain developmental processes by investigating their interactions with brain organoids. Our findings indicated that nanoplastics exposure caused cellular dysfunction and structural disorders. Nanoplastics adversely affected critical cells in brain organoids, resulting in the reduction of neural precursor cells and neuronal cells. The expression of neural cadherin was also inhibited, which might lead to impaired axonal extension and formation of synaptic connections. In addition, transcriptome sequencing was performed to study the effects of different concentrations of nanoplastics on the signaling pathway. The qRT-PCR analysis confirmed that nanoplastics exposure resulted in decreased expression of several genes related to the Wnt signaling pathway, suggesting that nanoplastics may adversely affect embryonic brain growth through the suppression of the expression of these genes. Our research findings shed light on the deleterious effects of nanoplastics on embryonic brain development and have significant implications for the field of environmental toxicology.

Electrons of d-orbital (Mn) and p-orbital (N) enhance the photocatalytic degradation of antibiotics by biochar while maintaining biocompatibility: A combined chemical and biological analysis.

Photocatalytic oxidation technology holds promise for ideal advanced treatment of antibiotic wastewater. Single-atom catalysts (SACs) are a new hotspot in catalytic science, but the photochemical studies on the removal of antibiotics from water and biocompatibility after entering the environment are scarce. In this work, we prepared a single Mn atom immobilized on N-doped biochar (Mn@N-Biochar) by impregnation calcination method for enhancing photocatalytic degradation of sulfanilamide (SNM) in different types of various water systems. Compared with the original biochar, Mn@N-Biochar showed enhanced SNM degradation and TOC removal capacity. DFT calculation concluded that the electrons of d-orbital (Mn) and p-orbital (N) altered the electronic structure of biochar and enhanced the photoelectric performance. It was shown that Mn@N-Biochar caused negligible systemic inflammation and tissue damage when given orally in mice, and also did not alter cell death and ROS production in human lung, kidney, and liver cells, as compared with biochar. We are convinced that Mn@N-Biochar could enhance the photocatalytic degradation of antibiotics while maintaining biocompatibility, which could be a promising strategy for wastewater treatment.

Construction and assessment of a joint prediction model and nomogram for colorectal cancer.

Background: Colorectal cancer (CRC) is one of the most common tumors in the digestive system, and all its risk factors are not yet known. It is important to identify valuable clinical indicators to predict the risk of CRC. Methods: A total of 227 participants, comprising 162 healthy adults and 65 patients diagnosed with CRC at Tianjin Hospital from January 2017 to March 2022, were included in this study. Electrochemiluminescence was adopted to test the expression levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA199). Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for CRC, and a joint prediction model was then constructed. A nomogram was prepared, and the model was later assessed using the receiver operating characteristic curve and calibration curve. Results: The univariate analysis showed that there were statistically significant differences between the two groups in terms of smoking (χ2=8.67), fecal occult blood (χ2=119.41), Helicobacter pylori (H. pylori) infection (χ2=30.87), a history of appendectomy (χ2=5.47), serum total bile acid levels (t=19.80), serum CEA levels (t=37.82), serum CA199 levels (t=6.82), and serum ferritin levels (t=54.31) (all P<0.05). The multiple logistic regression analysis showed that smoking, fecal occult blood, H. pylori infection, a history of appendectomy, serum CEA levels, and serum CA199 levels were independent risk factors for CRC (all P<0.05). Based on the above findings, a joint prediction model was constructed, and the area under the receiver operator characteristic (ROC) curve of the model was 0.842. A nomogram and calibration curve was drawn, and the internal validation results indicated that the model had good diagnostic value. Conclusions: Smoking, fecal occult blood, H. pylori infection, a history of appendectomy, serum CEA levels, and serum CA199 levels are independent risk factors for CRC, and the prediction model based on these factors had good predictive ability.

Bioinformatics analysis of Myelin Transcription Factor 1.

BACKGROUND AND OBJECTIVE: We aimed to further study the role of Myelin Transcription Factor 1(MyT1) in tumor and other diseases and epigenetic regulation, and better understand the regulatory mechanism of MyT1. METHODS: Using bioinformatics analysis, the structure and function of MyT1sequence were predicted and analyzed using bioinformatics analysis, and providing a theoretical basis for further experimental verification and understanding the regulatory mechanism of MyT1. The first, second and third-level structures of MyT1 were predicted and analyzed by bioinformatics analysis tools. RESULTS: MyT1 is found to be an unstable hydrophilic protein, rather than a secretory protein, with no signal peptide or trans-membrane domain; total amino acids located on the surface of the cell membrane. It contains seven zinc finger domains structurally. At sub-cellular level, MyT1 is localized in the nucleus. The phosphorylation site mainly exists in serine, and its secondary structure is mainly composed of random coils and alpha helices; the three-dimensional structure is analyzed by modeling. CONCLUSIONS: In this study, the structure and function of MyT1 protein were predicted, thereby providing a basis for subsequent expression analysis and functional research; it laid the foundation for further investigation of the molecular mechanism involved in the development of diseases.

Characterization of microvessels and parenchyma in in-line phase contrast imaging CT: healthy liver, cirrhosis and hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a cancer with a poor prognosis, and approximately 80% of HCC cases develop from cirrhosis. Imaging techniques in the clinic seem to be insufficient for revealing the microstructures of liver disease. In recent years, phase contrast imaging CT (PCI-CT) has opened new avenues for biomedical applications owing to its unprecedented spatial and contrast resolution. The aim of this study was to present three-dimensional (3D) visualization of human healthy liver, cirrhosis and HCC using a PCI-CT technique called in-line phase contrast imaging CT (ILPCI-CT) and to quantitatively evaluate the variations of these tissues, focusing on the liver parenchyma and microvasculature. METHODS: Tissue samples from 9 surgical specimens of normal liver (n=3), cirrhotic liver (n=2), and HCC (n=4) were imaged using ILPCI-CT at the Shanghai Synchrotron Radiation Facility (SSRF) without contrast agents. 3D visualization of all ex vivo liver samples are presented. To quantitatively evaluate the vessel features, the vessel branch angles of each sample were clearly depicted. Additionally, radiomic features of the liver parenchyma extracted from the 3D images were measured. To evaluate the stability of the features, the percent coefficient of variation (%COV) was calculated for each radiomic feature. A %COV <30 was considered to be low variation. Finally, one-way ANOVA, followed by Tukey's test, was used to determine significant changes among the different liver specimens. RESULTS: ILPCI-CT allows for a clearer view of the architecture of the vessels and reveals more structural details than does conventional radiography. Combined with the 3D visualization technique, ILPCI-CT enables the acquisition of an accurate description of the 3D vessel morphology in liver samples. Qualitative descriptions and quantitative assessment of microvessels demonstrated clear differences among human healthy liver, cirrhotic liver and HCC. In total, 38 (approximately 51%) radiomic features had low variation, including 11 first-order features, 16 GLCM features, 6 GLRLM features and 5 GLSZM features. The differences in the mean vessel branch angles and 3 radiomic features (first-order entropy, GLCM-inverse variance and GLCM-sum entropy) were statistically significant among the three groups of samples. CONCLUSIONS: ILPCI-CT may allow for morphologic descriptions and quantitative evaluation of vessel microstructures and parenchyma in human healthy liver, cirrhotic liver and HCC. Vessel branch angles and radiomic features extracted from liver parenchyma images can be used to distinguish the three kinds of liver tissues.

Metronomic photodynamic therapy with 5-aminolevulinic acid induces apoptosis and autophagy in human SW837 colorectal cancer cells.

Metronomic photodynamic therapy (mPDT) has emerged as an attractive treatment for the selective destruction of tumor cells by induction of apoptosis. Here, we compared the effects of mPDT and acute photodynamic therapy (aPDT) on human SW837 colorectal cancer (CRC) cells. CRC cells were subjected to mPDT using various exposure durations, concentrations of 5-aminolevulinic acid (ALA), fluence rates and energy densities. The effects were compared with those induced by aPDT. We found that apoptosis and autophagy were earlier induced to a greater extent by mPDT than by the same dose applied as aPDT. The survival rates for mPDT vs. aPDT were 35.2%, 32.4%,27.6%,31.6% vs. 85.7%, 71.1%, 67.8%, 42.1% after 3, 6, 12, and 24 h PDT, respectively. For the same time points, the apoptotic rates for mPDT vs. aPDT were 43.2%, 47.3%, 54.7%, and 50.3% vs. 14.6%, 17.6%, 27.1%, and 53.2%, respectively. mPDT induced a peak rate of autophagy of 20.0% at 3 h, whereas aPDT induced two smaller peaks at 3 h (14.1%) and 12 h (15.8%). Advanced autophagosomes were more abundant in mPDT- than aPDT-treated cells and appeared earlier after mPDT (3 h) than after aPDT (3-12 h). Western Bloting results showed that the ratio of LC3B-II/ß - actin at 3 h was higher (1.04 times) after mPDT than aPDT. Collectively, these datas indicated that ALA-mPDT was more effective than the same dose of ALA-aPDT at inducing SW837 CRC cell death via apoptosis and autophagy. Thus, mPDT may be a superior choice than aPDT for the treatment of human CRC.

Study on Umbilical Cord-Matrix Stem Cells Transplantation for Treatment of Acute Traumatic Brain Injury in Rats.

AIM: To evaluate the effect of umbilical cord derived mesenchymal stem cells (UC-MSCs) transplantation on traumatic brain injury (TBI). MATERIAL AND METHODS: UC-MSCs were isolated from human umbilical cord and TBI rat model was constructed. 30 male SD rats were randomly divided into 3 groups: control group, TBI group and MSCs transplantation group. Rats in MSCs group received the injection of a total of 1.5 C- 106 MSCs (25 I»l) via ventricle at operated ventricular coordinates (0 at bregma, 1.5 mm at lateral, 1.1 mm at behind, 4.5 mm in depth). RESULTS: 80% confluence of cells was formed from tissue at day 10 and the amount of CD90, CD73, CD105 positive cells increased correspondingly. In TBI model, clear hyperemia, edema and obvious infiltration of inflammatory cells in brain tissue were found. However, the manifestations were alleviated after the treatment of MSCs. In MSCs group, GFP in the brain tissue and the area around the vessels were found after the injection, while the expression levels of micro-vessel density (MVD), brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) were elevated. CONCLUSION: UC-MSCs transplantation for treatment of acute TBI could effectively reduce the injury and improve the vascular reconstruction.

Interleukin-1 in cerebrospinal fluid for evaluating the neurological outcome in traumatic brain injury.

Objective Severe traumatic brain injury (TBI) is associated with unfavorable outcomes secondary to injury from activation of the inflammatory cascade, the release of excitotoxic neurotransmitters, and changes in the reactivity of cerebral vessels, causing ischemia. Inflammation induced by TBI is complex, individual-specific, and associated with morbidity and mortality. The aim of the present study was to discover the differentially expressed cerebrospinal fluid (CSF) proteins and identify which can improve the clinical outcomes in TBI patients.Methods In the present study, we reported 145 patients with TBI and found the change in patients' leukocytes in serum and interleukin-1 (IL-1) in CSF, which strongly correlated with the neurological outcome. In terms of results of leukocytes in blood and IL-1 in CSF, we retained the patient's CSF specimens and conducted a proteomic analysis.Results A total of 119 differentially expressed proteins were detected between samples of TBI and the normal, which were commonly expressed in all samples, indicating the differentially expressed proteins. When the patients' Glasgow outcome score (GOS) improved, IL-1 was down-regulated, and when the patients' GCS score deteriorated, IL-1 was up-regulated accompanied with the progression in TBI.Conclusion The differentially expressed proteins in CSF may be the novel therapeutic targets for TBI treatment. The leukocytes in blood samples and the IL-1 in CSF may be two important indicators for predicting the prognosis of TBI patients.

3D printing collagen/chitosan scaffold ameliorated axon regeneration and neurological recovery after spinal cord injury.

Spinal cord injury (SCI) is a disaster that can cause severe motor, sensory, and functional disorders. Implanting biomaterials have been regarded as hopeful strategies to restore neurological function. However, no optimized scaffold has been available. In this study, a novel 3D printing technology was used to fabricate the scaffold with designed structure. The composite biomaterials of collagen and chitosan were also adopted to balance both compatibility and strength. Female Sprague-Dawley rats were subjected to a T8 complete-transection SCI model. Scaffolds of C/C (collagen/chitosan scaffold with freeze-drying technology) or 3D-C/C (collagen/chitosan scaffold with 3D printing technology) were implanted into the lesion. Compared with SCI or C/C group, 3D-C/C implants significantly promoted locomotor function with the elevation in Basso-Beattie-Bresnahan (BBB) score and angle of inclined plane. Decreased latency and increased amplitude were observed both in motor-evoked potential and somatosensory-evoked potential in 3D-C/C group compared with SCI or C/C group, which further demonstrated the improvement of neurological recovery. Fiber tracking of diffusion tensor imaging (DTI) showed the most fibers traversing the lesion in 3D-C/C group. Meanwhile, we observed that the correlations between the locomotor (BBB score or angle of inclined plane) and the DTI parameters (fractional anisotropy values) were positive. Although C/C implants markedly enhanced biotin dextran amine (BDA)-positive neural profiles compared with SCI group, rats implanted with 3D-C/C scaffold displayed the largest degree of BDA profiles regeneration. Collectively, our 3D-C/C scaffolds demonstrated significant therapeutic effects on rat complete-transected spinal cord model, which provides a promising and innovative therapeutic approach for SCI. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1898-1908, 2019.

Mechanism of interaction between ocular and nasal neurogenic inflammation in allergic rhinoconjunctivitis.

PURPOSE: The mechanisms of naso-ocular interaction in allergic rhinoconjunctivitis are not well understood. Neurogenic inflammation affects both eyes and nose via the same neurogenic factors. The purpose of this study was to investigate the effects of neurogenic inflammation on conjunctival inflammation following nasal allergen provocation. METHODS: Sensitized rats were exposed to ovalbumin (OVA) via the nose. Parts of the nasal mucosa and conjunctivae were sliced and used for hematoxylin-eosin staining, immunohistochemical analysis, western blotting, and real-time polymerase chain reaction. The slides were observed under a light microscope, and the acquired images were analyzed. The levels of substance P (SP), vasoactive intestinal peptide (VIP), and nerve growth factor (NGF) were detected. RESULTS: The levels of SP, VIP, and NGF were increased in both nasal mucosa and conjunctivae 1 h and 24 h after OVA administration (p < 0.05). Higher levels of SP, VIP, and NGF expression were observed in the nasal mucosa and conjunctivae 24 h after OVA administration (p < 0.05). Following damage of the nasal sensory nerves by capsaicin, the protein and mRNA levels of SP, VIP, and NGF were reduced. CONCLUSION: In conclusion, the increased levels of VIP, SP, and NGF might be responsible for the ocular reaction following nasal challenge with allergen in rats.

Effect of photobiomodulation on neural differentiation of human umbilical cord mesenchymal stem cells.

Photobiomodulation therapy (PBMT) can enhance the mesenchymal stem cell (MSC) proliferation, differentiation, and tissue repair and can therefore be used in regenerative medicine. The objective of this study is to investigate the effects of photobiomodulation on the directional neural differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) and provide a theoretical basis for neurogenesis. hUC-MSCs were divided into control, inducer, laser, and lasers combined with inducer groups. A 635-nm laser and an 808-nm laser delivering energy densities from 0 to 10 J/cm2 were used in the study. Normal cerebrospinal fluid (CSF) and injured cerebrospinal fluid (iCSF) were used as inducers. The groups were continuously induced for 3 days. Cellular proliferation was evaluated using MTT. The marker proteins nestin (marker protein of the neural precursor cells), NeuN (marker protein of neuron), and GFAP (glial fibrillary acidic protein, marker proteins of glial cells) were detected by immunofluorescence and western blot. We found that irradiation with 635-nm laser increased cell proliferation, and that with 808 nm laser by itself and combined with cerebrospinal fluid treatment generated significant neuron-like morphological changes in the cells at 72 h. Nestin showed high positive expression at 24 h in the 808 nm group. The expression of GFAP increased in the 808-nm combined inducer group at 24 h but decreased at 72 h. The expression of neuN protein increased only at 72 h in both the 808-nm combined inducer group and inducer group. We concluded that 808 nm laser irradiation could help CSF to induce neuronal differentiation of hUC-MSCs in early stage and tend to change to neuron rather than glial cells.

Effect of 405 nm low intensity irradiation on the absorption spectrum of in-vitro hyperlipidemia blood.

BACKGROUND: Laser therapy is reported to be clinically effective for improving microcirculation, rheological properties and blood lipid profiles despite the lack of certainty on the mechanism. OBJECTIVE: This study intends to provide methods to drop blood lipid level of hyperlipidemia samples by low-intensity laser irradiation therapy and provide reasoning of mechanism. METHODS: Twenty whole blood samples of high level of lipids profile are irradiated by 405 nm low-intensity laser at 12 J/cm2 twice a day for 3 days and compared with normal lipids profile group. Then whole blood sample are centrifuged to obtain result of erythrocyte for further interpretation. Multi-scan spectrum microplate reader is used to measure absorption spectrum and data is analyzed by software SPSS 14.0. RESULTS: Results show that after 405 nm low-intensity laser irradiation, whole blood samples of high lipid level statistically have higher absorbance peak value than normal samples while erythrocyte samples have lower absorbance peak value. CONCLUSIONS: From the divergence of absorption peak value change after low-intensity laser irradiation for whole blood sample and erythrocyte, we suspect that low level laser irradiation affects the enzymes activity of lipid metabolism, improves the cholesterol balance of plasma and cytoplasm in erythrocyte, and decreases aggregation of the erythrocyte.

Optical Depolarization of DCX-Expressing Cells Promoted Cognitive Recovery and Maturation of Newborn Neurons via the Wnt/ß-Catenin Pathway.

Electrical excitability by membrane depolarization is crucial for survival and maturation of newborn cells in the dentate gyrus of the hippocampus. However, traditional technology for membrane depolarization lacks temporal and spatial precision. Optogenetics can be used to activate channelrhodopsin-2 (ChR2), allowing cationic current to depolarize genetically targeted cells. In this study, we used ChR2-EGFP driven by doublecortin (DCX) to promote survival and maturation of newborn cells in the dentate gyrus after traumatic brain injury (TBI). C57BL/6 mice underwent lateral fluid percussion TBI. TBI mice were transfected with a lentivirus carrying the DCX-ChR2-EGFP gene. We observed that not only immature neurons but also type-2b intermediate progenitor (IPs) and neuroblasts expressed DCX-EGFP, indicating that DCX-expressing newborn cells could provide a long time window for electrical activity regulation. Quantitative results showed that the number of EGFP-expressing cells began to rise at 3 days after TBI and peaked at 9 days after TBI. By optical depolarization of DCX-EGFP-expressing cells between 3 and 12 days, we observed significantly improved cognitive deficits after TBI with enhanced survival and maturation of newborn cells in the dentate gyrus. We also investigated the role of optical depolarization in neural stem cells transfected with a lentivirus carrying the ChR2-DCX-EGFP gene in vitro. By administrating verapamil to block L-type calcium channels, we verified that the up-regulation of MAP2, NeuN, Neurog2, NeuroD1 and GluR2 in newborn cells was mediated by ChR2-elicted depolarization. By using ß-catenin inhibitor Dkk1, we demonstrated that optical depolarization of DCX-EGFP-expressing cells facilitated survival and maturation probably through the Wnt/ß-catenin signaling cascade.

Umbilical cord mesenchymal stem cell (UC-MSC) transplantations for cerebral palsy.

This study reports a case of a 4-year-old boy patient with abnormalities of muscle tone, movement and motor skills, as well as unstable gait leading to frequent falls. The results of the electroencephalogram (EEG) indicate moderately abnormal EEG, accompanied by irregular seizures. Based on these clinical characteristics, the patient was diagnosed with cerebral palsy (CP) in our hospital. In this study, the patient was treated with umbilical cord mesenchymal stem cell (UC-MSC) transplantation therapy. This patient received UC-MSC transplantation 3 times (5.3*107) in total. After three successive cell transplantations, the patient recovered well and showed obvious improvements in EEG and limb strength, motor function, and language expression. However, the improvement in intelligence quotient (IQ) was less obvious. These results indicate that UC-MSC transplantation is a promising treatment for cerebral palsy.