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Natural plant compounds with potent proliferation inhibition and apoptosis induction properties have been screened as novel anticancer drugs. Toxicarioside N (Tox N) was isolated from the seeds of the tropical plant Antiaris toxicaria in Hainan province, China. To our knowledge, the effects that Tox N has on the apoptosis of SGC-7901 cells and its potential mechanism have never been investigated. In this study, we detected the anticancer activities of Tox N and explored the potential mechanism in the human gastrointestinal cancer cell line SGC-7901. Here, we found that Tox N inhibited SGC-7901 cell growth in a dose- and time-dependent manner and induced apoptosis in cells based on cell morphology and flow cytometry analyses. Additionally, the SGC-7901 cell treated with Tox N up-regulated the expression level of cleaved caspase-3/9 and PARP, increased the Bax/Bcl-2 ratio, and led to the release of cytochrome c into the cytoplasm. In addition, Tox N treatment led to the phosphorylation of p38MAPK. SB203580, a p38MAPK inhibitor, partially attenuated Tox N induced apoptosis by preventing the activation of caspase-3/9 and PARP. Our results indicated for the first time that Tox N can induce SGC-7901 cells apoptosis by activating the p38MAPK pathway. [ABSTRACT FROM AUTHOR]

Vanadium oxides have aroused attention as cathode materials in aqueous zinc-ion batteries (AZIBs) due to their low cost and high safety. However, low ion diffusion and vanadium dissolution often lead to capacity decay and deteriorating stability during cycling. Herein, vanadium dioxides (VO 2 ) nanobelts are coated with a single-atom cobalt dispersed N-doped carbon (Co-N-C) layer via a facile calcination strategy to form Co-N-C layer coated VO 2 nanobelts (VO 2 @Co-N-C NBs) for cathodes in AZIBs. Various in-/ex situ characterizations demonstrate the interfaces between VO 2 layers and Co-N-C layers can protect the VO 2 NBs from collapsing, increase ion diffusion, and enhance the Zn 2+ storage performance. Additional density functional theory (DFT) simulations demonstrate that Co─O─V bonds between VO 2 and Co-N-C layers can enhance interfacial Zn 2+ storage. Moreover, the VO 2 @Co-N-C NBs provided an ultrahigh capacity (418.7 mAh g -1 at 1 A g -1 ), outstanding long-term stability (over 8000 cycles at 20 A g -1 ), and superior rate performance., (© 2023 Wiley‐VCH GmbH.)

Recovery from injury to the peripheral nervous system is different from that of the central nervous system in that it can lead to gene reprogramming that can induce the expression of a series of regeneration-associated genes. This eventually leads to axonal regeneration of injured neurons. Although some regeneration-related genes have been identified, the regulatory network underlying axon regeneration remains largely unknown. To explore the regulator of axon regeneration, we performed RNA sequencing of lumbar L4 and L5 dorsal root ganglion (DRG) neurons at different time points (0, 3, 6, 12 hours, 1, 3 and 7 days) after rat sciatic nerve crush. The isolation of neurons was carried out by laser capture microscopy combined with NeuN immunofluorescence staining. We found 1228 differentially expressed genes in the injured sciatic nerve tissue. The hub genes within these differentially expressed genes include Atf3, Jun, Myc, Ngf, Fgf2, Ezh2, Gfap and Il6. We verified that the expression of the enhancer of zeste homologue 2 gene (Ezh2) was up-regulated in DRG neurons after injury, and this up-regulation differed between large- and small-sized dorsal root ganglion neurons. To investigate whether the up-regulation of Ezh2 impacts axonal regeneration, we silenced Ezh2 with siRNA in cultured DRG neurons and found that the growth of the newborn axons was repressed. In our investigation into the regulatory network of Ezh2 by interpretive phenomenal analysis, we found some regulators of Ezh2 (including Erk, Il6 and Hif1a) and targets (including Atf3, Cdkn1a and Smad1). Our findings suggest that Ezh2, as a nerve regeneration-related gene, participates in the repair of the injured DRG neurons, and knocking down the Ezh2 in vitro inhibits the axonal growth of DRG neurons. All the experimental procedures approved by the Administration Committee of Experimental Animals of Jiangsu Province of China (approval No. S20191201-201) on March 21, 2019., Competing Interests: None

Glial cells play an important role in signal transduction, energy metabolism, extracellular ion homeostasis and neuroprotection of the central nervous system. However, few studies have explained the potential effects of exosomes from glial cells on central nervous system health and disease. In this study, the genes expressed in exosomes from astrocytes and microglia were identified by deep RNA sequencing. Kyoto Encyclopedia of Genes and Genomes analysis indicated that several pathways in these exosomes are responsible for promoting neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease. Gene ontology analysis showed that extracellular exosome, mitochondrion and growth factor activity were enriched in exosomes from the unique astrocyte group, while extracellular exosome and mitochondrion were enriched in exosomes from the unique microglia group. Next, combined with the screening of hub genes, the protein-protein interaction network analysis showed that exosomes from astrocytes influence neurodegenerative diseases through metabolic balance and ubiquitin-dependent protein balance, whereas exosomes from microglia influence neurodegenerative diseases through immune inflammation and oxidative stress. Although there were differences in RNA expression between exosomes from astrocytes and microglia, the groups were related by the hub genes, ubiquitin B and heat shock protein family A (Hsp70) member 8. Ubiquitin B appeared to be involved in pleiotropic regulatory functions, including immune regulation, inflammation inhibition, protein catabolism, intracellular protein transport, exosomes and oxidative stress. The results revealed the clinical significance of exosomes from glia in neurodegenerative diseases. This study was approved by the Animal Ethics Committee of Nantong University, China (approval No. S20180102-152) on January 2, 2018., Competing Interests: None

Neurological diseases such as stroke, Alzheimer's disease, Parkinson's disease, and Huntington's disease are among the intractable diseases for which appropriate drugs and treatments are lacking. Proteolysis targeting chimera (PROTAC) technology is a novel strategy to solve this problem. PROTAC technology uses the ubiquitin-protease system to eliminate mutated, denatured, and harmful proteins in cells. It can be reused, and utilizes the protein destruction mechanism of the cells, thus making up for the deficiencies of traditional protein degradation methods. It can effectively target and degrade proteins, including proteins that are difficult to identify and bind. Therefore, it has extremely important implications for drug development and the treatment of neurological diseases. At present, the targeted degradation of mutant BTK, mHTT, Tau, EGFR, and other proteins using PROTAC technology is gaining attention. It is expected that corresponding treatment of nervous system diseases can be achieved. This review first focuses on the recent developments in PROTAC technology in terms of protein degradation, drug production, and treatment of central nervous system diseases, and then discusses its limitations. This review will provide a brief overview of the recent application of PROTAC technology in the treatment of central nervous system diseases., Competing Interests: None

The peripheral nervous system has the potential to regenerate after nerve injury owing to the intrinsic regrowth ability of neurons and the permissive microenvironment. The regenerative process involves numerous gene expression changes, in which transcription factors play a critical role. Previously, we profiled dysregulated genes in dorsal root ganglion neurons at different time points (0, 3 and 9 hours, and 1, 4 and 7 days) after sciatic nerve injury in rats by RNA sequencing. In the present study, we investigated differentially expressed transcription factors following nerve injury, and we identified enriched molecular and cellular functions of these transcription factors by Ingenuity Pathway Analysis. This analysis revealed the dynamic changes in the expression of transcription factors involved in cell death at different time points following sciatic nerve injury. In addition, we constructed regulatory networks of the differentially expressed transcription factors in cell death and identified some key transcription factors (such as STAT1, JUN, MYC and IRF7). We confirmed the changes in expression of some key transcription factors (STAT1 and IRF7) by quantitative reverse transcription-polymerase chain reaction. Collectively, our analyses provide a global overview of transcription factor changes in dorsal root ganglia after sciatic nerve injury and offer insight into the regulatory transcription factor networks involved in cell death., Competing Interests: The authors declare that there are no conflicts of interest associated with this manuscript

Differential expression of miRNAs occurs in injured proximal nerve stumps and includes miRNAs that are firstly down-regulated and then gradually up-regulated following nerve injury. These miRNAs might be related to a Schwann cell phenotypic switch. miR-30c, as a member of this group, was further investigated in the current study. Sprague-Dawley rats underwent sciatic nerve transection and proximal nerve stumps were collected at 1, 4, 7, 14, 21, and 28 days post injury for analysis. Following sciatic nerve injury, miR-30c was down-regulated, reaching a minimum on day 4, and was then upregulated to normal levels. Schwann cells were isolated from neonatal rat sciatic nerve stumps, then transfected with miR-30c agomir and co-cultured in vitro with dorsal root ganglia. The enhanced expression of miR-30c robustly increased the amount of myelin-associated protein in the co-cultured dorsal root ganglia and Schwann cells. We then modeled sciatic nerve crush injury in vivo in Sprague-Dawley rats and tested the effect of perineural injection of miR-30c agomir on myelin sheath regeneration. Fourteen days after surgery, sciatic nerve stumps were harvested and subjected to immunohistochemistry, western blot analysis, and transmission electron microscopy. The direct injection of miR-30c stimulated the formation of myelin sheath, thus contributing to peripheral nerve regeneration. Overall, our findings indicate that miR-30c can promote Schwann cell myelination following peripheral nerve injury. The functional study of miR-30c will benefit the discovery of new therapeutic targets and the development of new treatment strategies for peripheral nerve regeneration., Competing Interests: None declared

To explore the clinical effect of Sanbitang recipe in treatment for the rheumatoid arthritis (RA) with kidney empty and cold-dampness symptom and its safety. A total 168 cases eligible patients were randomly divided into the traditional Chinese medicine (TCM) group, the chemical medicine group and the TCM combined with chemical medicine group, with 56 cases in each group. The TCM group was treated with Sanbitang recipe; The chemical medicine group was given methotrexate tablets; And Sanbitang recipe and methotrexate tablets was adopted in the TCM combined with chemical medicine group. A course of treatment was 16 weeks. Health assessment questionnaire (HAQ), disease activity scores 28-joint counts (DAS28), visual analogue scale (VAS), TCM symptom, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), cyclic citrullinated peptides (CCP) and rheumatoid factor (RF) were detected. The efficiencies and incidence of adverse reactions in the three groups were compared. The total effective rate of the TCM combined with chemical medicine group was 92.7%, which was higher than 79.2% of the TCM group and 82.4% of the chemical medicine group (P<0.05). There was no statistically significant difference between the TCM group and the chemical medicine group. This suggested that Sanbitang recipe was effective in treating rheumatoid arthritis (RA) with kidney empty and cold-dampness symptom. After treatment, the scores of HAQ, DAS28, VAS, ESR, CRP, CCP and RF of the TCM combined with chemical medicine group were significantly higher (P<0.05) among the three groups. There was no statistically significant difference between the TCM group and the chemical medicine group. This indicated that Sanbitang recipe could effectively alleviate the clinical symptoms of rheumatoid arthritis (RA) with kidney empty and cold-dampness symptom. In terms of efficiency and incidence of adverse reactions, the order from low to high was that the TCM group (3.8%, 2/53)

MicroRNAs (miRNAs) are small, non-coding RNAs that negatively adjust gene expression in multifarious biological processes. However, the regulatory effects of miRNAs on Schwann cells remain poorly understood. Previous microarray analysis results have shown that miRNA expression is altered following sciatic nerve transaction, thereby affecting proliferation and migration of Schwann cells. This study investigated whether miR-148b-3p could regulate migration of Schwann cells by directly targeting cullin-associated and neddylation-dissociated 1 (Cand1). Up-regulated expression of miR-148b-3p promoted Schwann cell migration, whereas silencing of miR-148b-3p inhibited Schwann cell migration in vitro. Further experiments confirmed that Cand1 was a direct target of miR-148b-3p, and Cand1 knockdown reversed suppression of the miR-148b-3p inhibitor on Schwann cell migration. These results suggested that miR-148b-3p promoted migration of Schwann cells by directly targeting Cand1 in vitro.

Objective: To explore the effects of SANPAOCAO (SPC), a compound traditional Chinese folk medicine, on chronic dermatitis/eczema in mice induced by 2, 4-dinitrochlorobenzene (DNCB)., Methods: Thirty-three Balb/c mice were randomly divided into a negative control group, a positive control group, a prednisolone treatment group, an SPC ethanol extract treatment group, a Cardiospermum halicacabum ethanol extract treatment group, a Physalis minima ethanol extract treatment group, and a Jussiaea repens ethanol extract treatment group. Mice in the six treatment groups had twenty-five microliters of 0.1% DNCB in acetone/olive oil (3: 1) applied to each side of their right ears and dorsal skin three times a week, over a 5 week period. They were treated with prednisolone or the various kinds of ethanol extract after each challenge. The weight difference between the two ears, pathological changes in the right ears, dermal inflammatory cell numbers, and total serum Ig E levels were used to assess the effects of the drugs., Results: after the 5 weeks of challenges, the weight differences of the ears in the SPC group and the prednisolone group were significantly less than those in the other groups. There was evidence of significant suppression of the development of dermatitis, as determined by a histological examination and the serum Ig E levels., Conclusion: SPC has beneficial effects when used in the treatment of chronic dermatitis-eczema in mice.

Objective: To observe the immune response induced by complex gene vaccine pcSAG1-ROP5 of Toxoplasma gondii in mice., Methods: The recombinant eukaryotic expression plasmids pcSAG1, pcROP5 and pcSAG1-ROP5 were constructed and identified by PCR, restriction enzyme digestion, and sequencing. The three recombinant plasmids were transfected into HeLa cells to express in vitro and identified by Western blotting analysis. Seventy Kunming mice were randomly divided into 5 groups with 14 each, i.e. pcSAG1 group, pcROP5 group, pcSAG1-ROP5 group, blank plasmid group and PBS control group. The mice were immunized intramuscularly with pcSAG1, pcROP5, pcSAG1-ROP5, pcDNA3.1, and PBS, respectively, every two weeks for three times. Sera were collected before each injection and 2 weeks after the last immunization. The titer of mice serum in pcSAG1-ROP5 group combined with recombinant protein SAG1, ROP5 and SAG1-ROP5 and the level of IgG against T. gondii in 5 groups were determined by ELISA. Three weeks after the last immunization, ten mice of each group were challenged with 10(3) tachyzoites of the virulent T. gondii RH strain to observe the survival time. One week later, the rest four mice in each group were sacrificed and the supernatant of cultured splenocytes was collected for the detection of IFN-gamma and IL-4., Results: Western blotting showed that the recombinant plasmids pcSAG1, pcROP5 and pcSAG1-ROP5 were expressed in HeLa cells with M(r) 31 000, 57 000, and 88 000, respectively. The serum titer in pcSAG1-ROP5 group combined with SAG1, ROP5 and SAG1-ROP5 was 1:320, 1:160, and 1:2560, respectively. The IgG level kept rising in pcSAG1, pcROP5 and pcSAG1-ROP5 groups. Two weeks after the last immunization, the IgG level in pcSAG1-ROP5 group was higher than those in other groups (P<0.05). After a lethal challenge of T. gondii RH strain, the survival time of the mice in pcSAG1-ROP5 group was (288 +/- 7) h, which was 48 h and 96h longer than the groups of pcSAG1 and pcROP5, respectively (P< 0.05). Four weeks after the last immunization, IFN-gamma in splenocyte culture of pcSAG1-ROP5 group [(908.52 +/- 6.31) pg/ml] was higher than other groups (P<0.05), with no significant difference in IL-4 (P>0.05)., Conclusion: Compared with the single gene vaccines pcSAG1 and pcROP5, higher levels of IgG and IFN-gamma and longer survival time are observed in mice immunized with pcSAG1-ROP5.

Objective: To study the antitumor efficacy of an immunoconjugate composed of adriamycin (ADM) and downsized Fab fragment of mouse anti-Endoglin monoclonal antibody., Methods: The Fab fragment of mouse anti-Endoglin monoclonal antibody was downsized and conjugated with ADM by m-Maleimidobenzoyl-N-hydroxysuccinimide ester (MBS). The antitumor effect of the conjugate was tested in mice bearing subcutaneous injection of H22 tumor in vivo., Results: The molecular ratio of Fab:ADM in conjugate was approximately 1:2. The Fab-ADM conjugate inhibited the growth of H22 by 91.94% on day 14 after injection at the dose of 0.4 mg/ kg, much higher the inhibition rate of 25.00% by the equivalent dose of free ADM. The median survival time of the mice treated with the conjugate was longer than those treated with free ADM. The Fab-ADM conjugate was significantly more effective than free ADM in tumor suppression and life span prolongation., Conclusion: Fab -ADM displayed more significant antitumor efficacy than free ADM in vivo and might be a novel candidate for cancer treatment.

Interleukin-5 (IL-5) involves in the development of airway inflammation and hyperresponsiveness through activation of eosinophils. Thus, inhibition of IL-5 expression seems to be an attractive approach for asthma therapy. In this study, an antisense IL-5 gene transferred by recombinant adeno-associated virus (asIL-5) was constructed to transfect murine allergic asthma model. Our results showed that asIL-5 efficiently inhibited the IL-5 mRNA expression and significantly attenuated the inflammation in lung tissues. Significant decreasing of eosinophils and inflammatory cells were found in peripheral blood and bronchoalveolar lavage fluid (BALF). In addition, significant inhibition of airway hyperresponsiveness (AHR) was also found in the mice treated with asIL-5. These observations demonstrate that antisense oligonucleotid against IL-5 delivered by adeno-associated virus system is possibly an efficacious therapeutic strategy for allergic asthma and other eosinophil-related disorders.