[Species of Chinese materia medica resources based on the fourth national survey of Chinese materia medica resources].

This article outlined the composition and species characteristics of Chinese materia medica(CMM) resources identified in the fourth national survey of CMM resources. The survey was conducted based on field investigations and office collation, adhering to the "four principles", which emphasized the existence of survey records, voucher specimens, actual photographs, and evidence of medicinal use, so as to summarize the species of CMM resources and ensure the scientific integrity and accuracy of the results. According to the results, China had a total of 18 817 CMM resources, including 15 321 medicinal plants, 826 medicinal fungi, 2 517 medicinal animals, and 153 medicinal minerals. Additionally, the fourth national survey of CMM resources also conducted specialized investigations on 3 151 species of unique medicinal plants, 464 species of rare and endangered medicinal plants, and 196 new species in China. These latest statistics on these CMM resources will provide the most up-to-date foundational data for the protection, management, development, and utilization of these resources over an extended period, offering scientific guidance for the development of the traditional Chinese medicine(TCM) industry.

MANF regulates neuronal survival and UPR through its ER-located receptor IRE1α.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-located protein with cytoprotective effects in neurons and pancreatic ß cells in vitro and in models of neurodegeneration and diabetes in vivo. However, the exact mode of MANF action has remained elusive. Here, we show that MANF directly interacts with the ER transmembrane unfolded protein response (UPR) sensor IRE1α, and we identify the binding interface between MANF and IRE1α. The expression of wild-type MANF, but not its IRE1α binding-deficient mutant, attenuates UPR signaling by decreasing IRE1α oligomerization; phosphorylation; splicing of Xbp1, Atf6, and Txnip levels; and protecting neurons from ER stress-induced death. MANF-IRE1α interaction and not MANF-BiP interaction is crucial for MANF pro-survival activity in neurons in vitro and is required to protect dopamine neurons in an animal model of Parkinson's disease. Our data show IRE1α as an intracellular receptor for MANF and regulator of neuronal survival.

Manual compression technique improves the success rate in the treatment of thrombosed aneurysmal arteriovenous fistula: A single-center experience.

OBJECTIVE: Endovascular intervention for thrombosed aneurysmal arteriovenous fistula (AVF) is still a challenge. Manual compression technique (MCT)-assisted angioplasty may be helpful, but there is no evidence or data to support it. METHODS: From January 2018 to May 2021, patients with thrombosed aneurysmal AVFs were retrospectively enrolled. The patients were separated into the MCT group or the traditional group according to the procedure received. Technical failure, clinical failure, 90-day patency, and safety were analyzed. RESULTS: A total of 159 cases (64 ± 12 years old, 60% male) were enrolled, of which 87 cases received MCT and 72 underwent traditional angioplasty. No technical failure was observed in the MCT group, while five technical failures were observed in the traditional group (0% vs. 7%, p = 0.02). There were no differences in the clinical failure rate (3% vs. 7%, p = 0.30), 90-day patency rate, or procedure time between the MCT group and the traditional group. There was no symptomatic pulmonary embolism or other complication in the two groups. CONCLUSION: MCT is a low-cost, less invasive, and safe procedure for thrombosed aneurysmal AVF, and it achieves a higher technical success rate than traditional angioplasty.

Cultivable endophytic fungal community associated with the karst endemic plant Nervilia fordii and their antimicrobial activity.

Endophytic fungi from medicinal plants with specific pharmacological functions attract much attention to provide the possibility of discovering valuable natural drugs with novel structures and biological activities. Nervilia fordii is a rare and endangered karst endemic plant that is used as medicine and food homology in Guangxi, China. These plants have been reported to have antimicrobial, antitumor, antiviral, and anti-inflammatory activities. However, few studies have focused on the diversity and antibacterial activity of endophytic fungi from N. fordii. In the present study, 184 endophytic fungi were isolated from the healthy tissues of N. fordii, and their molecular diversity and antimicrobial activities were analyzed for the first time. These fungi were categorized into 85 different morphotypes based on the morphological characteristics and the similarity between the target sequence and the reference sequence in the GenBank database. With the exception of 18 unidentified fungi, the fungal isolates belonged to at least 2 phyla, 4 classes, 15 orders, 45 known genera, and 45 different species, which showed high abundance, rich diversity, and obvious tissue specificity. All isolates were employed to screen for their antimicrobial activities via the agar diffusion method against Escherichia coli, Staphylococcus aureus, and Candida tropicalis. Among these endophytes, eight strains (9.41%) displayed inhibitory activity against E. coli, 11 strains (12.94%) against S. aureus, and two strains (2.35%) against C. tropicalis, to some extent. In particular, our study showed for the first time that the fungal agar plugs of Penicillium macrosclerotiorum 1151# exhibited promising antibacterial activity against E. coli and S. aureus. Moreover, the ethyl acetate (EA) extract of P. macrosclerotiorum 1151# had antibacterial effects against E. coli and S. aureus with a minimum inhibitory concentration (MIC) of 0.5 mg ml-1. Further research also confirmed that one of the antimicrobial compounds of P. macrosclerotiorum 1151# was methyl chloroacetate and exhibited excellent antibacterial activity against E. coli and S. aureus up to 1.71-fold and 1.13-fold compared with tetracycline (TET) (5 mg ml-1), respectively. Taken together, the present data suggest that various endophytic fungi of N. fordii could be exploited as sources of novel natural antimicrobial agents.

CDNF Interacts with ER Chaperones and Requires UPR Sensors to Promote Neuronal Survival.

Cerebral dopamine neurotrophic factor (CDNF) is a neurotrophic factor that has beneficial effects on dopamine neurons in both in vitro and in vivo models of Parkinson's disease (PD). CDNF was recently tested in phase I-II clinical trials for the treatment of PD, but the mechanisms underlying its neuroprotective properties are still poorly understood, although studies have suggested its role in the regulation of endoplasmic reticulum (ER) homeostasis and the unfolded protein response (UPR). The aim of this study was to investigate the mechanism of action of CDNF through analyzing the involvement of UPR signaling in its anti-apoptotic function. We used tunicamycin to induce ER stress in mice in vivo and used cultured primary neurons and found that CDNF expression is regulated by ER stress in vivo and that the involvement of UPR pathways is important for the neuroprotective function of CDNF. Moreover, we used AP-MS and BiFC to perform the first interactome screening for CDNF and report novel binding partners of CDNF. These findings allowed us to hypothesize that CDNF protects neurons from ER-stress-inducing agents by modulating UPR signaling towards cell survival outcomes.

Theoretical Study of a Two-Photon Fluorescent Probe Based on Nile Red Derivatives with Controllable Fluorescence Wavelength and Water Solubility.

Hypochloric acid (HOCl) plays a vital role in the natural defense system, but abnormal levels of it can cause cell damage, accelerated human aging, and various diseases. It is of great significance to develop new probes for detecting HOCl in biosystems nondestructively and noninvasively. The purpose of this work is to explore new chemical modification strategies of two-photon excitation fluorescence (TPEF) probes to improve the poor water solubility and low efficiency in imaging applications. Nil-OH-6 has a two-photon absorption cross-section value as high as 243 GM and attains a good quantum yield of 0.49. In addition, the modification of terminal groups with different azetidine-heterospirocycles or N,N-dialkyl fused amino groups to Nile Red can effectively improve the fluorescence efficiency as well as increase the solubility to some extent. This study provides some strategies to simultaneously improve the fluorescence performance and solubility of these two-photon probes and, hence, reliable guidance and a foundation for the subsequent synthesis of TPEF probes based on Nile Red.

[Selection of q RT-PCR reference genes for Amomum tsaoko seeds during dormancy release].

Freshly collected seeds of Amomum tsaoko demonstrate obvious dormancy. Therefore, the selection of stable reference genes during seed dormancy release is very important for the subsequent functional research of related genes. In this study, ten commonly used reference genes(GAPDH, 40S, actin, tubulin, EIF4A-9, EIF2α, UBC, UBCE2, 60S, and UBQ) were selected as candidates for quantitative Real-time polymerase chain reaction(qRT-PCR) of the embryo samples of A. tsaoko at different dormancy release stages. Three kinds of software(BestKeeper, geNorm, and Normfinder) and the Delta CT method were used to evaluate the expression stability of the candidate reference genes, and the RefFinder online tool was employed to integrate the results and generate a comprehensive ranking. The results showed that the expression levels of the ten candidate reference genes differed greatly in different embryo samples. GAPDH and UBC had high expression levels, as manifested by the small Ct values. GeNorm identified 40S and UBCE2 as the most stable genes. NormFinder ranked EIF2α as the most stable gene and UBC as the least stable gene. UBCE2 was found to be the most stable gene and actin the least stable one by BestKeeper. Delta CT analysis suggested that the expression of 40S was most stable. UBCE2 was recommended as the most stably expressed gene by RefFinder. Thus, UBCE2 is the ideal reference gene for qRT-PCR analysis of A. tsaoko seeds at different dormancy release stages. The results may lay a foundation for analyzing the expression of related genes during seed dormancy release of A. tsaoko.

[Genetic diversity and antibacterial activity of endophytic fungi from Zanthoxylum nitidum].

In order to reveal the distribution and population characteristics of endophytic fungi from Zanthoxylum nitidum and the antibacterial potential,this study performed molecular identification and analyzed the genetic diversity and antibacterial activity of endophytic fungi from Z. nitidum in Guangxi. Through culture and molecular identification,35 strains,belonging to 15 genera,12 families,10 orders,4 classes,and 2 phyla,were isolated from various tissues of Z. nitidum,of which Colletotrichum and Fusarium were the dominant genera,respectively accounting for 20% of total strains. The diversity of endophytic fungi was significantly different among roots,stems,and leaves,as manifested by the significantly higher Shannon index( H') in stems( 1. 678) than in roots( 0. 882 1) and leaves( 0. 515 4). The antimicrobial activity analysis showed that 14. 28% of endophytic fungi inhibited at least one indicator pathogen. Among them,Fusarium sp. ZN-34 and Fusarium sp. ZN-26 separately demonstrated the strongest inhibitory effect on Escherichia coli and Staphylococcus aureus. In general,Fusarium sp. ZN-26 and Phialemoniopsis plurioloculosa ZN-35 were advantageous in suppressing the two bacteria owing to the broad spectrum and strong efficacy. In summary,Z. nitidum in Guangxi boasts rich endophytic fungi with the majority showing strong antibacterial activity,which can be used as candidates for the extraction and separation of basic antibacterial substances and the development of natural antibacterial agents.

Small-Molecule Inhibitors of the RNA M6A Demethylases FTO Potently Support the Survival of Dopamine Neurons.

The fat mass and obesity-associated protein (FTO), an RNA N6-methyladenosine (m6A) demethylase, is an important regulator of central nervous system development, neuronal signaling and disease. We present here the target-tailored development and biological characterization of small-molecule inhibitors of FTO. The active compounds were identified using high-throughput molecular docking and molecular dynamics screening of the ZINC compound library. In FTO binding and activity-inhibition assays the two best inhibitors demonstrated Kd = 185 nM; IC50 = 1.46 µM (compound 2) and Kd = 337 nM; IC50 = 28.9 µM (compound 3). Importantly, the treatment of mouse midbrain dopaminergic neurons with the compounds promoted cellular survival and rescued them from growth factor deprivation induced apoptosis already at nanomolar concentrations. Moreover, both the best inhibitors demonstrated good blood-brain-barrier penetration in the model system, 31.7% and 30.8%, respectively. The FTO inhibitors demonstrated increased potency as compared to our recently developed ALKBH5 m6A demethylase inhibitors in protecting dopamine neurons. Inhibition of m6A RNA demethylation by small-molecule drugs, as presented here, has therapeutic potential and provides tools for the identification of disease-modifying m6A RNAs in neurogenesis and neuroregeneration. Further refinement of the lead compounds identified in this study can also lead to unprecedented breakthroughs in the treatment of neurodegenerative diseases.

Exploring factors influencing the retention of nurses in a religious hospital in Taiwan: a cross-sectional quantitative study.

BACKGROUND: Long-term deficits in the nursing labor force and high turnover rates are common in the Taiwanese medical industry. Little research has investigated the psychological factors associated with the retention of nursing staff. However, in practice, religious hospitals often provide nursing staff with education in medicine or the medical humanities to enhance their psychological satisfaction. The objective of this study was to explore factors influencing nursing staff retention in their work in relation to different levels of needs. A further objective was to investigate whether medical humanities education was associated with the retention of nursing staff. METHODS: This study used self-administrated questionnaires to survey nurses working in northern areas of Taiwan. The questionnaire design was based on the six levels of Maslow's hierarchy of needs. Participation was voluntary, and the participants signed informed consent documents. Self-administrated questionnaires were distributed to a total of 759 participants, and 729 questionnaires were returned (response rate 96.04%). Logistic regression analysis was used to estimate the impact of seniority on nurses' reported intention to stay after adjustment for nurse characteristics (gender and age). RESULTS: In the Pearson correlation analysis, nurses' willingness to stay was moderately correlated with "physical needs", "safety needs", "love and belonging needs", and "esteem needs" (r = 0.559, P < 0.001; r = 0.533, P < 0.001; r = 0.393, P < 0.001; and r = 0.476, P < 0.001, respectively). Furthermore, nurses' willingness to stay was highly correlated with "self-actualization needs", "beyond self-actualization needs" and "medical humanities education-relevant needs" (r = 0.707, P < 0.001; r = 0.728, P < 0.001; and r = 0.678, P < 0.001, respectively). We found that the odds ratios (ORs) of retention of nursing staff with less than 1 year (OR = 4.511, P = 0.002) or 1-3 years (OR = 3.248, P = 0.003) of work experience were significantly higher than that of those with 5-10 years of work experience. CONCLUSIONS: With regard to medical humanities education, we recommend adjusting training, as the compulsory activities included in the official programs are inadequate, and adjusting the number of required hours of medical humanities education. Tailoring different educational programs to different groups (especially nurses who have worked 3-5 years or 5-10 years in the case study hospital) might improve acceptance by nursing staff.

The cytoprotective protein MANF promotes neuronal survival independently from its role as a GRP78 cofactor.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-stress-regulated protein exhibiting cytoprotective properties through a poorly understood mechanism in various in vitro and in vivo models of neuronal and non-neuronal damage. Although initially characterized as a secreted neurotrophic factor for midbrain dopamine neurons, MANF has recently gained more interest for its intracellular role in regulating the ER homeostasis, including serving as a cofactor of the chaperone glucose-regulated protein 78 (GRP78). We aimed for a better understanding of the neuroprotective mechanisms of MANF. Here we show for the first time that MANF promotes the survival of ER-stressed neurons in vitro as a general unfolded protein response (UPR) regulator, affecting several UPR pathways simultaneously. Interestingly, MANF does not affect naïve neurons. We hypothesize that MANF regulates UPR signaling toward a mode more compatible with neuronal survival. Screening of MANF interacting proteins from two mammalian cell lines revealed a conserved interactome of 15 proteins including several ER chaperones such as GRP78, GRP170, protein disulfide isomerase family A member 1, and protein disulfide isomerase family A member 6. Further characterization confirmed previously published finding that MANF is a cofactor of GRP78 interacting with its nucleotide binding domain. Using microscale thermophoresis and nuclear magnetic resonance spectroscopy, we discovered that MANF is an ATP binding protein and that ATP blocks the MANF-GRP78 interaction. Interestingly, functional analysis of the antiapoptotic properties of MANF mutants in cultured neurons revealed divergent roles of MANF as a GRP78 cofactor and as an antiapoptotic regulator of UPR. We conclude that the co-factor type interaction with GRP78 is dispensable for the survival-promoting activity of MANF in neurons.

A more effective catalysis of the CO2 fixation with aziridines: computational screening of metal-substituted HKUST-1.

A vital issue for the fixation and conversion of CO2 into useful chemical products is to find effective catalysts. In this work, in order to develop more effective and diverse catalysts, we implemented the first computational screening study (at M06-2X//B3LYP level) on the cycloaddition of CO2 with aziridines under eighteen metal-substituted HKUST-1 MOFs and tetrabutylammonium bromide (TBAB) as a co-catalyst. For all considered catalytic systems, the ring-opening of aziridine is calculated to be the rate-determining step. Up to 11 M-HKUST-1 systems, i.e., Rh (31.87 kcal mol-1), Y (31.02), Sc (30.50), V (30.02), Tc (29.90), Cd (29.80), Ti (29.32), Mn (29.05), Zn (28.29), Fe (27.85) and Zr (25.09), possess lower ring-opening barrier heights than the original Cu-HKUST-1 (32.90), indicative of their superior catalytic ability to the original Cu-HKUST-1 in theory. With the lowest ring-opening barrier, Zr-HKUST-1 is strongly advocated for future synthetic and catalytic studies.

Netrin-1 and its receptor DCC modulate survival and death of dopamine neurons and Parkinson's disease features.

The netrin-1/DCC ligand/receptor pair has key roles in central nervous system (CNS) development, mediating axonal, and neuronal navigation. Although expression of netrin-1 and DCC is maintained in the adult brain, little is known about their role in mature neurons. Notably, netrin-1 is highly expressed in the adult substantia nigra, leading us to investigate a role of the netrin-1/DCC pair in adult nigral neuron fate. Here, we show that silencing netrin-1 in the adult substantia nigra of mice induces DCC cleavage and a significant loss of dopamine neurons, resulting in motor deficits. Because loss of adult dopamine neurons and motor impairments are features of Parkinson's disease (PD), we studied the potential impact of netrin-1 in different animal models of PD. We demonstrate that both overexpression of netrin-1 and brain administration of recombinant netrin-1 are neuroprotective and neurorestorative in mouse and rat models of PD. Of interest, we observed that netrin-1 levels are significantly reduced in PD patient brain samples. These results highlight the key role of netrin-1 in adult dopamine neuron fate, and the therapeutic potential of targeting netrin-1 signaling in PD.

Characterization of the complete chloroplast genome of Plumeria rubra cv. Acutifolia (Apocynaceae).

Plumeria rubra cv. Acutifolia is a widely planted landscape tree in the subtropics. In this study, the complete chloroplast genome of P. rubra cv. Acutifolia was determined through Illumina sequencing method. The complete chloroplast genome has a length of 153,912 bp, containing a small single-copy region (18,036 bp), a large single-copy region (84,852 bp), and a pair of IR regions (25,512 bp). The chloroplast genome possesses 130 genes, including 85 CDS, 37 tRNA genes and 8 rRNA genes. P. rubra cv. Acutifolia exhibited the closest relationship with P. cubensis in phylogenetic analysis.

The Efficacy of Traditional Chinese Medicine Shoutai Pill Combined with Western Medicine in the First Trimester of Pregnancy in Women with Unexplained Recurrent Spontaneous Abortion: A Systematic Review and Meta-Analysis.

BACKGROUND: Shoutai Pill (STP), a famous classic herbal formula documented in traditional Chinese medicine (TCM), is widely available in China for treating unexplained recurrent spontaneous abortion (URSA). This systematic review and meta-analysis aims at evaluating the efficacy and safety of STP in the first trimester of pregnancy in women with a history of unexplained recurrent spontaneous abortion. METHODS: The following eight databases were searched from their establishment to Dec 31, 2019, for randomized controlled trials (RCTs): PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese BioMedical database (CBM), Chinese Scientific Journal Database (VIP), and the Wanfang database. The quality of evidence was estimated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: A total of 12 studies (916 patients) with URSA were contained in this meta-analysis. The forest plot showed that patients treated with Shoutai Pill and western medicine had a significantly lower incidence of early pregnancy loss (RR: 0.42; 95% CI: 0.34-0.52; P < 0.01, I 2 = 0%). Subgroup analysis revealed that different types of TCM syndrome differentiation had the similar results. Also, in the combined group, patients had a lower TCM syndromes and symptoms and serum D-dimer level, while higher incidence of live birth. CONCLUSIONS: Our findings suggest that cotreatment with STP and western medicine might be superior to western medicine alone in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent spontaneous abortion, and there was no adverse event in the experimental group reported. However, the methodological quality of included RCTs was unsatisfactory; it is necessary to verify its effectiveness with further more standardized researches of rigorous design.

Efficacy of Traditional Chinese Medicine Tonifying Kidney (Bushen) and Activating Blood (Huoxue) Prescription for Premature Ovarian Insufficiency: A Systematic Review and Meta-Analysis.

OBJECTIVE: We carried out this systematic review and meta-analysis to evaluate the effectiveness of TKABP on POI. METHODS: The following eight databases were searched from the establishment to September 30, 2019, for randomized controlled trials (RCTs): PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese BioMedical database (CBM), Chinese Scientific Journal Database (VIP), and the Wanfang database. The quality of evidence was estimated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: Twenty-three RCTs involving 1712 patients with POI were included. Compared to hormone therapy (HT) groups, TKABP groups showed a significantly higher total effective rate (RR: 1.10; 95% CI: 1.04-1.17; P < 0.01, I 2 = 32%). In addition, TKABP groups revealed a better improvement in terms of serum follicle-stimulating hormone (FSH) levels, serum estradiol (E2) levels, peak systolic velocity (PSV) of ovarian stromal blood, and Kupperman index (KI) score. However, serum luteinizing hormone (LH) levels and ovarian volume (OV) showed no significant statistical difference. Subgroup analyses showed that herbal paste and 3 months of treatment duration had a greater effect on the improvement of hormone levels. Besides, the occurrence of related adverse events in TKABP groups was lower than that in HT groups. CONCLUSIONS: Our review suggests that TKABP appears to be an effective and safe measure for patients with POI, and the herbal paste may be superior. However, the methodological quality of included RCTs was unsatisfactory, and it is necessary to verify its effectiveness with furthermore standardized researches of rigorous design.

[Effects of exogenous IBA and fungal elicitor on growth of in vitro roots culture of Dysosma versipellis and production of podophyllotoxin].

Using the White as basic medium, the effects of the exogenous IBA and endophytic fungal elicitor on the growth of in vitro roots cultures of Dysosma versipellis and production of podophyllotoxin were investigated in this study. The results showed that the IBA and the endophytic fungus Zasmidium syzygii elicitor could increase the content of podophyllotoxin of in vitro roots of D. versipellis after 3 weeks. The White medium added with 3 mg·L~(-1) IBA induced the highest increase of podophyllotoxin(1 830.86 µg·g~(-1)), which was 2.07 folds greater than the control, and followed by 1.5 mg·L~(-1) IBA, fungal elicitor, 1 mg·L~(-1) IBA, 0.5 mg·L~(-1) IBA and 4.5 mg·L~(-1) IBA, which was 1.82, 1.71, 1.63, 1.43 and 1.1 folds greater than the control, respectively. The results also showed that the growth of roots was certain positively correlated with the change of IBA concentration. Therefore, 3 mg·L~(-1) IBA was the most suitable for the production of podophyllotoxin in the in vitro roots of D. versipellis, and the stimulating effect of Z. syzygii fungal elicitor was between 1.5 mg·L~(-1) and 1 mg·L~(-1) IBA, which was a potential natural elicitor to induce the accumulation of podophyllotoxin in future production.

[Inhibitory effect of endophytic fungi from Dysosma versipellis on HIV-1 IN-LEDGF/p75 interaction].

To determine the inhibitory effect of endophytic fungi from Dysosma versipellis on HIV-1 IN-LEDGF/p75 interaction,the protein-protein interaction between human immunodeficiency virus type 1( HIV-1) integrase and lens epithelial growth factor p75 protein( LEDGF/p75) was used as a target. The homogeneous time-resolved fluorescence( HTRF) technique was used in the inhibitory activity assay. The results showed that eight endophytic fungi with anti-IN-LEDGF/p75 interaction activity were screened out from fifty-three strains with different morphological characteristic. Among them,106 strain showed strong inhibitory activity against HIV-1 IN-LEDGF/p75 interaction with IC50 value of 5. 23 mg·L-1,and was identified as a potential novel species of Magnaporthaceae family by the analyses of ITS-rDNA,LSU and RPB2 sequences data. This study demonstrated that potential natural active ingredients against the HIV-1 IN-LEDGF/p75 interaction exist in the endophytic fungi of D. versipellis. These results may provide available candidate strain resources for the research and development of new anti-acquired immunodeficiency syndrome drugs.

Antioxidative CXXC Peptide Motif From Mesencephalic Astrocyte-Derived Neurotrophic Factor Antagonizes Programmed Cell Death.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a potent survival-promoting protein with neurorestorative effect for neurodegenerative diseases. Its mechanism of action, albeit poorly known, depends strongly on the CXXC motif (CKGC). Here we studied the survival-promoting properties of the CKGC tetrapeptide from MANF. In the Jurkat T lymphocytic cell line, CKGC potently inhibits death receptor Fas-induced apoptosis and mildly counteracts mitochondrial apoptosis and necroptosis. The peptide with serines instead of cysteines (SKGS) has no survival-promoting activity. The cytoprotective efficiency of the peptide against Fas-induced apoptosis is significantly improved by reduction of its cysteines by dithiotreitol, suggesting that it protects the cells via cysteine thiol groups, partially as an antioxidant. CKGC neutralizes the reactive oxygen species, maintains the mitochondrial membrane potential and prevents activation of the effector caspases in the Jurkat cells with activated Fas. The peptide does not require intracellular administration, as it is endocytosed and resides mainly in the Golgi. Finally, the peptide also potently promotes survival of cultured primary dopaminergic neurons.

Author Correction: Diversity and bioactive potential of culturable fungal endophytes of Dysosma versipellis; a rare medicinal plant endemic to China.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.