Network pharmacology analysis and animal experiment validation of neuroinflammation inhibition by total ginsenoside in treating CSM.

BACKGROUND: Cervical spondylotic myelopathy (CSM) is a degenerative pathology that affects both upper and lower extremity mobility and sensory function, causing significant pressure on patients and society. Prior research has suggested that ginsenosides may have neuroprotective properties in central nervous system diseases. However, the efficacy and mechanism of ginsenosides for CSM have yet to be investigated. PURPOSE: This study aims to analyze the composition of ginsenosides using UPLC-MS, identify the underlying mechanism of ginsenosides in treating CSM using network pharmacology, and subsequently confirm the efficacy and mechanism of ginsenosides in rats with chronic spinal cord compression. METHODS: UPLC-Q-TOF-MS was utilized to obtain mass spectrum data of ginsenoside samples. The chemical constituents of the samples were analyzed by consulting literature reports and relevant databases. Ginsenoside and CSM targets were obtained from the TCMSP, OMIM, and GeneCards databases. GO and KEGG analyses were conducted, and a visualization network of ginsenosides-compounds-key targets-pathways-CSM was constructed, along with molecular docking of key bioactive compounds and targets, to identify the signaling pathways and proteins associated with the therapeutic effects of ginsenosides on CSM. Chronic spinal cord compression rats were intraperitoneally injected with ginsenosides (50 mg/kg and 150 mg/kg) and methylprednisolone for 28 days, and motor function was assessed to investigate the therapeutic efficacy of ginsenosides for CSM. The expression of proteins associated with TNF, IL-17, TLR4/MyD88/NF-κB, and NLRP3 signaling pathways was assessed by immunofluorescence staining and western blotting. RESULTS: Using UPLC-Q-TOF-MS, 37 compounds were identified from ginsenoside samples. Furthermore, ginsenosides-compounds-key targets-pathways-CSM visualization network indicated that ginsenosides may modulate the PI3K-Akt signaling pathway, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, Toll-like receptor signaling pathway and Apoptosis by targeting AKT1, TNF, MAPK1, CASP3, IL6, and IL1B, exerting a therapeutic effect on CSM. By attenuating neuroinflammation through the TNF, IL-17, TLR4/MyD88/NF-κB, and MAPK signaling pathways, ginsenosides restored the motor function of rats with CSM, and ginsenosides 150 mg/kg showed better effect. This was achieved by reducing the phosphorylation of NF-κB and the activation of the NLRP3 inflammasome. CONCLUSIONS: The results of network pharmacology indicate that ginsenosides can inhibit neuroinflammation resulting from spinal cord compression through multiple pathways and targets. This finding was validated through in vivo tests, which demonstrated that ginsenosides can reduce neuroinflammation by inhibiting NLRP3 inflammasomes via multiple signaling pathways, additionally, it should be noted that 150 mg/kg was a relatively superior dose. This study is the first to verify the intrinsic molecular mechanism of ginsenosides in treating CSM by combining pharmacokinetics, network pharmacology, and animal experiments. The findings can provide evidence for subsequent clinical research and drug development.

Long-term in vivo chimeric cells tracking in non-human primate.

Non-human primates (NHPs) are increasingly used in preclinical trials to test the safety and efficacy of biotechnology therapies. Nonetheless, given the ethical issues and costs associated with this model, it would be highly advantageous to use NHP cellular models in clinical studies. However, developing and maintaining the naïve state of primate pluripotent stem cells (PSCs) remains difficult as does in vivo detection of PSCs, thus limiting biotechnology application in the cynomolgus monkey. Here, we report a chemically defined, xeno-free culture system for culturing and deriving monkey PSCs in vitro. The cells display global gene expression and genome-wide hypomethylation patterns distinct from monkey-primed cells. We also found expression of signaling pathways components that may increase the potential for chimera formation. Crucially for biomedical applications, we were also able to integrate bioluminescent reporter genes into monkey PSCs and track them in chimeric embryos in vivo and in vitro. The engineered cells retained embryonic and extra-embryonic developmental potential. Meanwhile, we generated a chimeric monkey carrying bioluminescent cells, which were able to track chimeric cells for more than 2 years in living animals. Our study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models for clinical studies.

Boosting the Plasmon-Mediated Electrochemical Oxidation of p-Aminothiophenol with p-Hydroxythiophenol as Molecular Cocatalyst.

Plasmon-mediated electrochemistry is an emerging area of interest in which the electrochemical reactions are enhanced by employing metal nanostructures possessing localized surface plasmon resonance (LSPR). However, the reaction efficacy is still far below its theoretical limit due to the ultrafast relaxation of LSPR-generated hot carriers. Herein, we introduce p-hydroxythiophenol (PHTP) as a molecular cocatalyst to significantly improve the reaction efficacy in plasmon-mediated electrochemical oxidation of p-aminothiophenol (PATP) on gold nanoparticles. Using electrochemical techniques, in situ Raman spectroscopy, and theoretical calculations, we elucidate that the presence of PHTP improves the hot hole-mediated electrochemical oxidation of PATP by 2-fold through the trapping of plasmon-mediated hot electrons. In addition, the selectivity of PATP oxidation could also be modulated by the introduction of PHTP cocatalyst. This tactic of employing molecular cocatalyst can be drawn out to endorse various plasmonic electrochemical reactions because of its simple protocol, high efficiency, and high selectivity.

Selectively Adsorbed p-Aminothiophenol Molecules Improve the Electrocatalytic and Photo-Electrocatalytic Hydrogen Evolution on Au/TiO2.

Electrocatalytic hydrogen evolution reaction (HER) is receiving increasing attention as an effective process to produce clean energy. The commonly used precious metal catalysts can be hybridized with semiconductors to form heterostructures for the improvement of catalytic efficiency and reduction of cost. It will be promising to further improve the efficiency of heterostructure-based nanocatalysts in electrocatalytic and photocatalytic HER using a simple and effective method. Herein, we improve the efficiency of Au/TiO2 in electrocatalytic and photo-electrocatalytic HER by selectively adsorbing p-aminothiophenol (PATP) molecules. The PATP molecules are adsorbed on the gold surface by using a simple solution-based method and favor the charge separation at the Au-TiO2 interface. We also compare the PATP molecules with other thiophenol molecules in the enhancement of electrocatalytic HER. The PATP-induced enhancement in electrocatalysis is then further investigated by density functional theory (DFT) calculations, and this enhancement is attributed to a reduction in Gibbs energy of adsorbed hydrogen after surface adsorption of PATP molecules. This work provides a simple, cost-effective, and highly efficient approach to improve the electrocatalytic and photo-electrocatalytic efficiency of Au/TiO2, and this approach could be easily extended to other heterostructure-based nanocatalysts for performance enhancement and may be used in many other catalytic reactions.

A systematic review and meta-analysis of chondroitinase ABC promotes functional recovery in rat models of spinal cord injury.

BACKGROUND: To comprehensively assess the neurologic recovery potential of chondroitinase ABC (ChABC) in rats after spinal cord injury (SCI). METHODS: The PubMed, Embase, ScienceDirect, Web of Science, and China National Knowledge Infrastructure databases were searched for animal experiments that evaluated the use of ChABC in the treatment of SCI up to November 2022. Studies reporting neurological function using the Basso, Beattie, and Bresnahan (BBB) scale, as well as assessments of cavity area, lesion area, and glial fibrillary acidic protein (GFAP) levels, were included in the analysis. RESULTS: A total of 46 studies were ultimately selected for inclusion. The results of the study showed that rats with SCI that received ChABC therapy exhibited a significant improvement in locomotor function after 7 days compared with controls (32 studies, weighted mean difference (WMD) = 0.58, [0.33, 0.83], p < 0.00001). Furthermore, the benefits of ChABC therapy were maintained for up to 28 days according to BBB scale. The lesion area was reduced by ChABC (5 studies, WMD = -20.94, [-28.42, -13.46], p < 0.00001). Meanwhile, GFAP levels were reduced in the ChABC treatment group (8 studies, WMD = -29.15, [-41.57, -16.72], p < 0.00001). Cavity area is not statistically significant. The subgroup analysis recommended that a single injection of 10 µL (8 studies, WMD = 2.82, [1.99, 3.65], p < 0.00001) or 20 U/mL (4 studies, WMD = 2.21, [0.73, 3.70], p = 0.003) had a better effect on improving the function. The funnel plot of the BBB scale was found to be essentially symmetrical, indicating a low risk of publication bias. CONCLUSIONS: This systematic review and meta-analysis has indicated that ChABC could improve functional recovery in rats after SCI.

A comprehensive and systematic review of the potential neuroprotective effect of quercetin in rat models of spinal cord injury.

CONTEXT: Spinal cord injury (SCI) is a potentially fatal neurological disease with severe complications and a high disability rate. An increasing number of animal experimental studies support the therapeutic effect of quercetin, which is a natural anti-inflammatory and antioxidant bioflavonoid. OBJECTIVE: This paper reviewed the therapeutic effect of quercetin on a rat SCI model and summarized the relevant mechanistic research. DATA SOURCES: PubMed, EMBASE, Web of Science, Science Direct, WanFang Data, SinoMed databases, the China National Knowledge Infrastructure, and the Vip Journal Integration Platform were searched from their inception to April 2023 for animal experiments applying quercetin to treat SCI. STUDY SELECTION: Based on the PICOS criteria, a total of 18 eligible studies were included, of which 14 were high quality. RESULTS: In this study, there was a gradual increase in effect based on the Basso, Beattie, and Bresnahan (BBB) score after three days (p < 0.0001). Furthermore, gender differences also appeared in the efficacy of quercetin; males performed better than females (p = 0.008). Quercetin was also associated with improved inclined plane test score (p = 0.008). In terms of biochemical indicators, meta-analysis showed that MDA (p < 0.0001) and MPO (p = 0.0002) were significantly reduced after quercetin administration compared with the control group, and SOD levels were increased (p = 0.004). Mechanistically, quercetin facilitates the inhibition of oxidative stress, inflammation, autophagy and apoptosis that occur after SCI. CONCLUSIONS: Generally, this systematic review suggests that quercetin has a neuroprotective effect on SCI.

Analysis of gene expression profiles and experimental validations of a rat chronic cervical cord compression model.

Cervical spondylotic myelopathy (CSM) is a severe non-traumatic spinal cord injury (SCI) wherein the spinal canal and cervical cord are compressed due to the degeneration of cervical tissues. To explore the mechanism of CSM, the ideal model of chronic cervical cord compression in rats was constructed by embedding a polyvinyl alcohol-polyacrylamide hydrogel in lamina space. Then, the RNA sequencing technology was used to screen the differentially expressed genes (DEGs) and enriched pathways among intact and compressed spinal cords. A total of 444 DEGs were filtered out based on the value of log2(Compression/Sham); these were associated with IL-17, PI3K-AKT, TGF-ß, and Hippo signaling pathways according to the GSEA, KEGG, and GO analyses. Transmission electron microscopy indicated the changes in mitochondrial morphology. Western blot and immunofluorescence staining revealed neuronal apoptosis, astrogliosis and microglial neuroinflammation in the lesion area. Specifically, the expression of apoptotic indicators, such as Bax and cleaved caspase-3, and inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, were upregulated. The activation of IL-17 signaling pathway was observed in microglia instead of neurons or astrocytes, the activation of TGF-ß and inhibition of Hippo signaling pathways were detected in astrocytes instead of neurons or microglia, and the inhibition of PI3K-AKT signaling pathway was discovered in neurons rather than microglia of astrocytes in the lesion area. In conclusion, this study indicated that neuronal apoptosis was accompanied by inhibiting of the PI3K-AKT pathway. Then, the activation of microglia IL-17 pathway and NLRP3 inflammasome effectuated the neuroinflammation, and astrogliosis was ascribed to the activation of TGF-ß and the inhibition of the Hippo pathway in the chronic cervical cord of compression. Therefore, therapeutic methods targeting these pathways in nerve cells could be promising CSM treatments.

Strong synergy between gold nanoparticles and cobalt porphyrin induces highly efficient photocatalytic hydrogen evolution.

The reaction efficiency of reactants near plasmonic nanostructures can be enhanced significantly because of plasmonic effects. Herein, we propose that the catalytic activity of molecular catalysts near plasmonic nanostructures may also be enhanced dramatically. Based on this proposal, we develop a highly efficient and stable photocatalytic system for the hydrogen evolution reaction (HER) by compositing a molecular catalyst of cobalt porphyrin together with plasmonic gold nanoparticles, around which plasmonic effects of localized electromagnetic field, local heating, and enhanced hot carrier excitation exist. After optimization, the HER rate and turn-over frequency (TOF) reach 3.21 mol g-1 h-1 and 4650 h-1, respectively. In addition, the catalytic system remains stable after 45-hour catalytic cycles, and the system is catalytically stable after being illuminated for two weeks. The enhanced reaction efficiency is attributed to the excitation of localized surface plasmon resonance, particularly plasmon-generated hot carriers. These findings may pave a new and convenient way for developing plasmon-based photocatalysts with high efficiency and stability.

Melatonin restores endoplasmic reticulum homeostasis to protect injured neurons in a rat model of chronic cervical cord compression.

Cervical spondylotic myelopathy (CSM) refers to a chronic injury of the cervical cord caused by cervical intervertebral disc degeneration. Endoplasmic reticulum (ER) homeostasis is essential to counteract neuronal apoptosis. ER stress, an integral part of ER homeostasis, was observed in a rat model of chronic cervical cord compression in our previous study. However, the correlation between ER homeostasis and CSM remains unknown. The antioxidant melatonin is known to exert therapeutic effects in acute spinal cord injury, but the specific effects and their potential mechanisms in the pathological processes of CSM require further exploration. The present study hypothesized that ER homeostasis is essential for neuronal apoptosis in the CSM and that melatonin maintains this homeostasis. The results showed that ER stress led to neuronal apoptosis in rats with chronic cervical cord compression. Conversely, melatonin attenuates protein kinase R-like ER kinase-eukaryotic initiation factor 2α-C/EBP-homologous protein, inositol-requiring enzyme 1, and transcription factor 6 signaling pathways to release ER stress and prevents Bax translocation to the mitochondrion, thereby promoting motor recovery and protecting neurons in vivo. It also rescued primary rat cortical neurons from ER stress-induced glutamate toxicity in vitro. Moreover, melatonin remodels the ER morphology and restores homeostasis via ER-phagy in injured neurons. FAM134B, CCPG1, RTN3, and Sec. 62 are four known ER-phagy receptors. In this study, Sec. 62 was identified as a key melatonin factor in promoting ER-phagy and restoring ER homeostasis in damaged neurons in vivo and in vitro. In conclusion, melatonin suppresses neuronal apoptosis by reducing ER stress and promoting ER-phagy to restore ER morphology and homeostasis. The current results suggested that melatonin is a promising treatment for CSM owing to its restorative effect on ER homeostasis; however, well-designed randomized controlled trials must be carried out to further investigate its clinical effects.

Adsorbed p-Aminothiophenol Molecules on Platinum Nanoparticles Improve Electrocatalytic Hydrogen Evolution.

Electrocatalytic hydrogen evolution is an important approach to produce clean energy, and many electrocatalysts (e.g., platinum) are developed for hydrogen production. However, the electrocatalytic efficiency of commonly used metal catalysts needs to be improved to compensate their high cost. Herein, the electrocatalytic efficiency of platinum nanoparticles (PtNPs) in hydrogen evolution is largely improved via simple surface adsorption of sub-monolayer p-aminothiophenol (PATP) molecules. The overpotential goes down to 86.1 mV, which is 50.2 mV lower than that on naked PtNPs. This catalytic activity is even better than that of 20 wt.% Pt/C, despite the much smaller active surface area of PATP-adsorbed PtNPs than Pt/C. It is theoretically and experimentally confirmed that the improved electrocatalytic activity in hydrogen evolution can be attributed to the change in electronic structure of PtNPs induced by surface adsorption of PATP molecules. More importantly, this strategy can also be used to improve the electrocatalytic activity of palladium, gold, and silver nanoparticles. Therefore, this work provides a simple, convenient, and versatile method for improving the electrocatalytic activity of metal nanocatalysts. This surface adsorption strategy may also be used for improving the efficiency of many other nanocatalysts in many reactions.

Chronic spinal cord compression associated with intervertebral disc degeneration in SPARC-null mice.

Chronic spinal cord compression (CSCC) is induced by disc herniation and other reasons, leading to movement and sensation dysfunction, with a serious impact on quality of life. Spontaneous disc herniation rarely occurs in rodents, and therefore establishing a chronic spinal cord compression (CSCC) animal model is of crucial importance to explore the pathogenesis and treatment of CSCC. The absence of secreted protein, acidic, and rich in cysteine (SPARC) leads to spontaneous intervertebral disc degeneration in mice, which resembles human disc degeneration. In this study, we evaluated whether SPARC-null mice may serve as an animal model for CSCC. We performed rod rotation test, pain threshold test, gait analysis, and Basso Mouse Scale score. Our results showed that the motor function of SPARC-null mice was weakened, and magnetic resonance images revealed compression at different spinal cord levels, particularly in the lumbar segments. Immunofluorescence staining and western blot assay showed that the absence of SPARC induced apoptosis of neurons and oligodendrocytes, activation of microglia/macrophages with M1/M2 phenotype and astrocytes with A1/A2 phenotype; it also activated the expression of the NOD-like receptor protein 3 inflammasome and inhibited brain-derived neurotrophic factor/tyrosine kinase B signaling pathway. Notably, these findings are characteristics of CSCC. Therefore, we propose that SPARC-null mice may be an animal model for studying CSCC caused by disc herniation.

Cross-cultural adaptation of The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire: A methodological systematic review.

BACKGROUND: The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) is a reliable and sensitive measure of disability to determine functional status and evaluate curative effects in low back pain, it has now been cross-cultural translated into many other languages and adapted for use in different countries. We aim to evaluate the translation procedures and measurement properties of cross-cultural adaptations of the JOABPEQ. METHODS: Studies related to cross-cultural adaptation of the JOABPEQ in a specific language/culture were searched in PubMed, Embase, CINAHL, SciELO, PsycINFO, SinoMed, and Web of Science from their inception to March 2022. The Guidelines for the Process of Cross-Cultural Adaptation of Self-Report Measures and the Consensus-based Standards for the Selection of Health Status Measurement Instruments guideline were used for evaluation. RESULTS: Nine different versions of cross-cultural JOABPEQ adaptations in 8 different languages/cultures were included. The adaptation process was not strictly performed, such as standard forward translation and expert committee review were rarely reported. Content validity (8/9), floor and ceiling effects (3/9), reliability (4/9), and interpretability (6/9) were assessed in most of the adaptations, while agreement (2/9), responsiveness (2/9), and the internal consistency (2/9) were not. JOABPEQ can replace functional and quality of life score to reduce the burden of scientific research. CONCLUSION: We recommend Persian-Iranian, simplified Chinese-Chinese Mandarin, Thai and Gunaydin G's Turkish adaptations for application. The numerical pain rating scale/visual analogue scale in low back pain and lower extremities, as well as numbness in lower extremities could not be neglected in JOABPEQ adaptations.

Selective adsorption of cysteamine molecules on Au/TiO2 boosts visible light-driven photocatalytic hydrogen evolution.

Photocatalytic evolution of hydrogen is becoming a research hotspot because it can help to produce clean energy and reduce environmental pollution. Titanium dioxide (TiO2) and its composites are photocatalysts that are widely used in hydrogen evolution because of their high abundance in nature, low price, and high photo/chemical stability. However, their catalytic performances still need to be further improved, particularly in the visible light spectrum. Herein, visible light-driven photocatalytic evolution of hydrogen on Au/TiO2 nanocomposite is enhanced âˆ¼ 10 folds by selectively functionalizing the nanocomposite with cysteamine molecules. It is revealed that the amine group (-NH2) in cysteamine favors the transfer and separation of photo-generated hot carriers. The rate of hydrogen produced can be further tuned by varying the ionization of the functionalized molecules at different pH values. This work provides a simple, convenient, and effective method that can be used to improve the photocatalytic evolution of hydrogen. This method can also be used for many other nanocatalysts (e.g., Au-MoS2, Au-BiVO4) and catalytic reactions (e.g., carbon dioxide reduction, nitrogen reduction).

Current state of stem cell research in non-human primates: an overview.

The remarkable similarity between non-human primates (NHPs) and humans establishes them as essential models for understanding human biology and diseases, as well as for developing novel therapeutic strategies, thereby providing more comprehensive reference data for clinical treatment. Pluripotent stem cells such as embryonic stem cells and induced pluripotent stem cells provide unprecedented opportunities for cell therapies against intractable diseases and injuries. As continue to harness the potential of these biotechnological therapies, NHPs are increasingly being employed in preclinical trials, serving as a pivotal tool to evaluate the safety and efficacy of these interventions. Here, we review the recent advancements in the fundamental research of stem cells and the progress made in studies involving NHPs.

Clinical Characteristics and Treatment Overview in Hand-Foot-and-Mouth Disease Using Real-World Evidence Based on Hospital Information System.

Objectives: To describe the epidemiological characteristics and medication overview of HFMD in Guangzhou and analyze the factors of length of stay (LOS) based on TCM usage. Method: From January 1, 2014, to June 30, 2019, clinical data of HFMD (ICD-10 B08.401) as the initial diagnosis, based on HIS of five medical institutions for outpatient and inpatient cases, was collected. The inpatient cases of the five hospitals in Guangzhou were utilized for hospitalization analysis. Information extracted from the warehouse was standardized. Descriptive analysis was used for baseline characteristics, medication usage, and inpatient characteristics. Potential factors were analyzed by bivariate analysis. COX regression analysis and Kaplan-Meier analysis for calculating HRs and 95% CIs were adopted to determine the predictors of LOS. Stratified COX regression was applied to analyze the relationship between predictors and LOS and to calculate interaction. Results: A total of 14172 patients with HFMD were included. It showed that HFMD would occur in males, infants, and summer. Cause and symptoms are the two aspects of conventional Western medicine treatments, while TCM treatment of HFMD took clearing heat and detoxification as the basic principle. Inpatients with HFMD were divided into two groups by the use ratio of TCM. Age, season, and disease severity were possible correlated factors of LOS, extrapolating from their disparity in distribution. By stratified Cox regression, three factors following presented as possible contributions to shortening LOS, including TCM ≥ 0.1 (HR = 1.79, 95% CI (1.67-1.92), P < 0.01), winter (HR = 1.28, 95% CI (1.12-1.47)), P < 0.01), mild HFMD (HR = 1.93, 95% CI (1.69-2.22), P < 0.01). Additive interaction of TCM use and disease severity was significant (RERI = 1.014 (0.493-1.534), P < 0.01). Conclusion: Young children and high temperature were the risk factors of HFMD infection, which suggests that increasing surveillance for susceptible particular-age individuals and season is indispensable. Favorable factors to decrease LOS included a higher proportion of TCM use, mild HFMD, and onset in winter. The proportion of TCM use had additive interaction with disease severity, indicating that TCM may have antiviral and other biological effects on HFMD. Increasing the proportion of TCM use was probably beneficial to shortening LOS.

Comprehensive analysis of clinical prognosis and CLIC1 immune invasion in lung adenocarcinoma.

BACKGROUND: Chloride intracellular channel 1 (CLIC1) plays an important role in the process of cell epithelial transport, and is also involved in tumor invasion and metastasis. Due to its aberrant expression in cancer, the mechanism of action of CLIC1 in cancer has been carefully studied. In this study, we tried to investigate the relationship between CLIC1 and lung adenocarcinoma (LUAD). METHODS: The RNA-sequencing data and clinical information of CLIC1 in lung adenocarcinoma were collected from the the cancer genome altas (TCGA) database and analyzed with R software. Paired t test and Mann-Whitney U test were used to detect differences between LUAD tissue and adjacent normal tissue, and the pROC software package performed reactive oxygen species (ROC) curves to detect cutoff values for CLIC1. The expression of CLIC1 in normal human tissues was extracted from the human protein altas (HPA) database, and analyzed clinical proteomic tumor analysis consortium by using UALCAN programme. The relationship between CLIC1 and LUAD was explored by enrichment analysis using gene oncology and Kyoto encyclopedia of genes and genomes. The tumor immunity estimation resource (TIMER) and integrated repository portal for tumor-immune system interactions (TISIDB) databases were used to analyze the correlation between CLIC1 and LUAD immune cell infiltration. Survival analysis of CLIC1 in LUAD was assessed by the PrognoScan database. RESULTS: Compared with normal tissues, both mRNA (messenger Ribose Nucleic Acid) and protein of CLIC1 were overexpressed in LUAD, which was associated with shorter overall survial (OS). In addition, CLIC1 expression was in connection with some clinical-pathological characteristics like tumor node metatasis stages and lymph node metastases. What's more, CLIC1 may play a role in the immune infiltration of LUAD. CONCLUSION: In summary, CLIC1 is up-regulated in LUAD and is associated with tumor metastasis, tumor staging, and OS. It may be regarded as a novel marker for prognostic judgement in LUAD.

Neuroprotective Effect and Possible Mechanisms of Ginsenoside-Rd for Cerebral Ischemia/Reperfusion Damage in Experimental Animal: A Meta-Analysis and Systematic Review.

Ischemic stroke, the most common type of stroke, can lead to a long-term disability with the limitation of effective therapeutic approaches. Ginsenoside-Rd (G-Rd) has been found as a neuroprotective agent. In order to investigate and discuss the neuroprotective function and underlying mechanism of G-Rd in experimental animal models following cerebral ischemic/reperfusion (I/R) injury, PubMed, Embase, SinoMed, and China National Knowledge Infrastructure were searched from their inception dates to May 2022, with no language restriction. Studies that G-Rd was used to treat cerebral I/R damage in vivo were selected. A total of 18 articles were included in this paper, and it was showed that after cerebral I/R damage, G-Rd administration could significantly attenuate infarct volume (19 studies, SMD = -1.75 [-2.21 to - 1.30], P < 0.00001). Subgroup analysis concluded that G-Rd at the moderate doses of >10- <50 mg/kg reduced the infarct volume to the greatest extent, and increasing the dose beyond 50 mg/kg did not produce better results. The neuroprotective effect of G-Rd was not affected by other factors, such as the animal species, the order of administration, and the ischemia time. In comparison with the control group, G-Rd administration could improve neurological recovery (lower score means better recovery: 14 studies, SMD = -1.50 [-2.00 to - 1.00], P < 0.00001; higher score means better recovery: 8 studies, SMD = 1.57 [0.93 to 2.21], P < 0.00001). In addition, this review suggested that G-Rd in vivo can antagonize the reduced oxidative stress, regulate Ca2+, and inhibit inflammatory, resistance to apoptosis, and antipyroptosis on cerebral I/R damage. Collectively, G-Rd is a promising natural neuroprotective agent on cerebral I/R injury with unique advantages and a clear mechanism of action. More clinical randomized, blind-controlled trials are also needed to confirm the neuroprotective effect of G-Rd on cerebral I/R injury.

Mechanisms of Intervertebral Disc Degeneration Treatment with Deer Antlers Based on Network Pharmacology and Molecular Docking.

Background: With the aging of the population, the prevalence of IVDD increases preoperatively. How to better treat IVDD has become an important clinical issue. Deer antlers proved to have a great effect on the treatment of IVDD in many studies, but the molecular mechanism has not been clarified. Objective: To investigate the molecular mechanism and target of deer antlers in the treatment of IVDD. Methods: Compounds from deer antlers were collected and targets were predicted using HERB, TCMSP, TCMID, SwissADME, and SwissTargetPrediction. Collection of disease targets for IVDD was done using GeneCards, TTD, DrugBank, DisGeNET, and OMIM. Cytoscape 3.7.2, AutoDock Vina (v1.1.2), and R software were used for data analysis and the construction of network diagrams. Results: A total of 5 active compounds from deer antlers were screened and 104 therapeutic targets were predicted. A total of 1023 IVDD disease targets were collected. Subsequently, PPI network prediction analysis was performed for disease and treatment targets, and 112 core targets were collected after screening. After obtaining the core target, we used the clusterProfiler software package of R software to carry out GO and KEGG enrichment analyses for the core target and plot the bubble maps. According to the GO enrichment results, the main biological processes of IVDD treatment by deer antlers lie in the rhythmic process, mRNA catabolic process, and G1/S transition of the mitotic cell cycle. KEGG results were mainly related to the PI3K-Akt signaling pathway, thyroid hormone signaling pathway, and Notch signaling pathway. Molecular docking results showed that estrone had the best docking results on ESR1. Conclusion: Deer antlers are rich in various compounds that can prevent the development of IVDD by upregulating the PI3K-Akt signaling pathway and Notch signaling pathway. Its key compounds estradiol and estrone can reduce the inflammatory response and oxidative stress in tissues and organs, thus slowing down the progression of IVDD. Estrone, the active compound in deer antlers, was found by molecular docking to have good results against ESR1, the target of the disease, which may be a potential site for drug therapy.

Molecular Cocatalyst of p-Mercaptophenylboronic Acid Boosts the Plasmon-Mediated Reduction of p-Nitrothiophenol.

Localized surface plasmon resonance (LSPR) has been demonstrated to be highly effective in the initialization or acceleration of chemical reactions because of its unique optical properties. However, because of the ultrashort lifetime (fs to ps) of plasmon-generated hot carriers, the potential of LSPR in photochemical reactions has not been fully exploited. Herein, we demonstrate an acceleration of the plasmon-mediated reduction of p-nitrothiophenol (PNTP) molecules on the surface of silver nanoparticles (AgNPs) with in situ Raman spectroscopy. p-Mercaptophenylboronic acid (PMPBA) molecules coadsorbed on AgNP surfaces act as a molecular cocatalyst in the plasmon-mediated reaction, resulting in a boosting of the PNTP reduction. This boosting is attributed to the improved transfer and separation of the plasmon-generated hot carriers at the interface of the AgNPs and coadsorbed PMPBA molecules. Our finding provides a highly simple, cost-effective, and highly effective strategy to promote plasmonic photochemistry by introducing a molecular cocatalyst, and this strategy can be extended to promote various plasmon-mediated reactions.

Neuroinflammation and apoptosis after surgery for a rat model of double-level cervical cord compression.

INTRODUCTION: Cervical spondylotic myelopathy (CSM) is the most prevalent type of non-traumatic spinal cord injury. The pathological process of CSM is relatively complicated. Most of the chronic cervical cord compression animal models established using hydrophilic expanding polymer are single-segment compression, which was deviated from clinical practice with double-segment or multi-segment compression. This study aims to better mimic the actual clinical compression by using a new type of hydrophilic expanding polymer to establish an animal model of double-level cervical cord compression. MATERIALS AND METHODS: Progressive cord compression was done with implantation of polyvinyl alcohol-polyacrylamide hydrogel in the spinal canal at the C3-4 and C5-6 levels. Sprague-Dawley rats (n = 32) were divided into three groups: sham (no compression, n = 12) and screw compression group (n = 8), and hydrogel compression group (n = 12). Functional deficits were characterized using motor function scores, forelimb grip strength, hindlimb pain threshold, and gait analysis, while compression was imaged with magnetic resonance imaging. The apoptosis, inflammation, and demyelination were assessed by hematoxylin and eosin staining, Luxol fast blue staining, TUNEL assay, immunofluorescence staining, and Western blot analysis. RESULTS: Motor function scores for rats with cervical cord hydrogel compression were significantly decline in motor function scores, an increase in allodynia, neurons and oligodendrocytes apoptosis related to B cell lymphoma-2 (Bcl-2)/Bcl-2 associated X (Bax)/cleaved caspase-3, and impaired axonal conduction, as well as neuroinflammation zone related to microglia or macrophages aggregation related to the nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome activation, and activation of astrocytes, as well as oxidative stress were observed. CONCLUSION: We believe that this model utilizing compression on double-level cervical cord will allow researchers to investigate of translationally relevant therapeutic methods for CSM.