Regulation of mitophagy and mitochondrial function: Natural compounds as potential therapeutic strategies for Parkinson's disease.

Mitochondrial damage is associated with the development of Parkinson's disease (PD), indicating that mitochondrial-targeted treatments could hold promise as disease-modifying approaches for PD. Notably, natural compounds have demonstrated the ability to modulate mitochondrial-related processes. In this review article, we discussed the possible neuroprotective mechanisms of natural compounds against PD in modulating mitophagy and mitochondrial function. A comprehensive literature search on natural compounds related to the treatment of PD by regulating mitophagy and mitochondrial function was conducted from PubMed, Web of Science and Chinese National Knowledge Infrastructure databases from their inception until April 2023. We summarize recent advancements in mitophagy's molecular mechanisms, including upstream and downstream processes, and its relationship with PD-related genes or proteins. Importantly, we highlight how natural compounds can therapeutically regulate various mitochondrial processes through multiple targets and pathways to alleviate oxidative stress, neuroinflammation, Lewy's body aggregation and apoptosis, which are key contributors to PD pathogenesis. Unlike the single-target strategy of modern medicine, natural compounds provide neuroprotection against PD by modulating various mitochondrial-related processes, including ameliorating mitophagy by targeting the PINK1/parkin pathway, the NIX/BNIP3 pathway, and autophagosome formation (i.e., LC3 and p62). Given the prevalence of mitochondrial damage in various neurodegenerative diseases, exploring the exact mechanism of natural compounds on mitophagy and mitochondrial dysfunction could shed light on the development of highly effective disease-modifying or adjuvant therapies targeting PD and other neurodegenerative disorders.

Endogenous crude Scutellaria baicalensis polysaccharide robustly enhances one-pot extraction and deglycosylation of baicalin.

With the extensive application of baicalein in the treatment of cardiovascular and cerebrovascular diseases, its clinical and market demand has gradually expanded. But the natural yield of baicalein is very low, and it is mainly prepared by the deglycosylation of baicalin. However, the insolubility of baicalin in water significantly limits the deglycosylation of it under biocatalysis. To make biocatalysis of baicalin more efficient and environmental, a strategy was designed to enhance its water solubility through the solubilization mechanism of endogenous biological macromolecules, and the effect on the activity of glucuronidase was further explored. The results showed that wrapping with Scutellaria baicalensis polysaccharide (SBP) significantly improved the solubility of baicalin in water (the water solubility of baicalin increased by 23 times, BI/SBP = 1/12, w/w). It was not only contributed to the efficient production of baicalein by one-pot method, but also effectively improved the deglycosylation rate of baicalin (increase by 47.04 % in aqueous solution). With the help of the solubilization of endogenous polysaccharide on baicalin in aqueous solution, a green, low-cost and efficient method (one-pot method) was designed to simultaneously extract and enzymatic hydrolyze baicalin to prepare baicalein. Under the same conditions, the yield of one-pot method is 87.17 %, which was much higher than that of the conventional method (29.38 %). In addition, one-pot method with the aid of endogenous polysaccharide could simply and conveniently prepare aglycone of other insoluble natural flavonoids, which has a wide range of industrial application value.

Historical Review of Acute Pancreatitis Research Over the Last 80 Years.

OBJECTIVES: Research on acute pancreatitis (AP) has been ongoing for a long time. It is necessary to summarize and investigate the history of AP research. METHODS: Publications related to AP research were retrieved from PubMed. Medical Subject Headings (MeSH) terms, countries, journals, and publication dates were analyzed. Co-occurrence analysis was conducted to illustrate the holistic trend in AP research. A dynamic bar graph, heat maps, and line charts were created to illustrate change trends of MeSH terms. RESULTS: In total, 28,222 publications with 8558 MeSH terms were retrieved from 1941 to 2020. Among these, 16,575 publications with 7228 MeSH terms were from 2001 to 2020. The top 10 MeSH terms showed a considerable change from 1941 to 1970 but remained stable since the 1970s. Four clusters obtained from the co-occurrence analysis were "experiments on animals," "diagnosis and treatment," "prognosis and expectation," and "protein and enzyme." From 1941 to 2020, 33 MeSH terms with increasing trends (MH-I) and 15 MeSH terms with decreasing trends (MH-D) were selected to create a heat map (every decade). Meanwhile, 16 MH-I and 41 MH-D were selected to create the heat map from 2001 to 2020 (every 2 years). CONCLUSION: Over the past 80 years, the pathogenesis, treatment, risk management, and experimental model were the main research highlights. Optimal supportive management, minimally invasive treatment, and prediction of prognosis are subjects of interest for clinical practitioners; signal transduction to identify a target for precise treatment is the focus of experimental research in AP.

Super-high procoagulant activity of gecko thrombin: A gift from sky dragon.

AIMS: Gecko, the "sky dragon" named by Traditional Chinese Medicine, undergoes rapid coagulation and scarless regeneration following tail amputation in the natural ecology, providing a perfect opportunity to develop the efficient and safe drug for blood clotting. Here, gecko thrombin (gthrombin) was recombinantly prepared and comparatively studied on its procoagulant activity. METHODS: The 3D structure of gthrombin was constructed using the homology modeling method of I-TASSER. The active gthrombin was prepared by the expression of gecko prethrombin-2 in 293 T cells, followed by purification with Ni2+ -chelating column chromatography prior to activation by snake venom-derived Ecarin. The enzymatic activities of gthrombin were assayed by hydrolysis of synthetic substrate S-2238 and the fibrinogen clotting. The vulnerable nerve cells were used to evaluate the toxicity of gthrombin at molecular and cellular levels. RESULTS: The active recombinant gthrombin showed super-high catalytic and fibrinogenolytic efficiency than those of human under different temperatures and pH conditions. In addition, gthrombin made nontoxic effects on the central nerve cells including neurons, contrary to those of mammalian counterparts, which contribute to neuronal damage, astrogliosis, and demyelination. CONCLUSIONS: A super-high activity but safe procoagulant candidate drug was identified from reptiles, which provided a promising perspective for clinical application in rapid blood clotting.

Potential Inhibitors of Monkeypox Virus Revealed by Molecular Modeling Approach to Viral DNA Topoisomerase I.

The monkeypox outbreak has become a global public health emergency. The lack of valid and safe medicine is a crucial obstacle hindering the extermination of orthopoxvirus infections. The identification of potential inhibitors from natural products, including Traditional Chinese Medicine (TCM), by molecular modeling could expand the arsenal of antiviral chemotherapeutic agents. Monkeypox DNA topoisomerase I (TOP1) is a highly conserved viral DNA repair enzyme with a small size and low homology to human proteins. The protein model of viral DNA TOP1 was obtained by homology modeling. The reliability of the TOP1 model was validated by analyzing its Ramachandran plot and by determining the compatibility of the 3D model with its sequence using the Verify 3D and PROCHECK services. In order to identify potential inhibitors of TOP1, an integrated library of 4103 natural products was screened via Glide docking. Surface Plasmon Resonance (SPR) was further implemented to assay the complex binding affinity. Molecular dynamics simulations (100 ns) were combined with molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) computations to reveal the binding mechanisms of the complex. As a result, three natural compounds were highlighted as potential inhibitors via docking-based virtual screening. Rosmarinic acid, myricitrin, quercitrin, and ofloxacin can bind TOP1 with KD values of 2.16 µM, 3.54 µM, 4.77 µM, and 5.46 µM, respectively, indicating a good inhibitory effect against MPXV. The MM/PBSA calculations revealed that rosmarinic acid had the lowest binding free energy at -16.18 kcal/mol. Myricitrin had a binding free energy of -13.87 kcal/mol, quercitrin had a binding free energy of -9.40 kcal/mol, and ofloxacin had a binding free energy of -9.64 kcal/mol. The outputs (RMSD/RMSF/Rg/SASA) also indicated that the systems were well-behaved towards the complex. The selected compounds formed several key hydrogen bonds with TOP1 residues (TYR274, LYS167, GLY132, LYS133, etc.) via the binding mode analysis. TYR274 was predicted to be a pivotal residue for compound interactions in the binding pocket of TOP1. The results of the enrichment analyses illustrated the potential pharmacological networks of rosmarinic acid. The molecular modeling approach may be acceptable for the identification and design of novel poxvirus inhibitors; however, further studies are warranted to evaluate their therapeutic potential.

Flavonoid-Rich Extract of Oldenlandia diffusa (Willd.) Roxb. Inhibits Gastric Cancer by Activation of Caspase-Dependent Mitochondrial Apoptosis.

OBJECTIVE: To evaluate the apoptosis and cycle arrest effects of Oldenlandia diffusa flavonoids on human gastric cancer cells, determine the action mechanisms in association with the mitochondrial dependent signal transduction pathway that controls production of reactive oxygen species (ROS), and evaluate the pharmacodynamics of a mouse xenotransplantation model to provide a reference for the use of flavonoids in prevention and treatment of gastric cancer. METHODS: Flavonoids were extracted by an enzymatic-ultrasonic assisted method and purified with D-101 resin. Bioactive components were characterized by high-performance liquid chromatography. Cell lines MKN-45, AGS, and GES-1 were treated with different concentrations of flavonoids (64, 96, 128, 160 µg/mL). The effect of flavonoids on cell viability was evaluated by MTT method, and cell nuclear morphology was observed by Hoechst staining. The apoptosis rate and cell cycle phases were measured by flow cytometry, the production of ROS was detected by laser confocal microscope, the mitochondrial membrane potential (MMP) were observed by fluorescence microscope, and the expression of apoptotic proteins related to activation of mitochondrial pathway were measured by immunoblotting. MKN-45 cells were transplanted into BALB/c nude mice to establish a xenograft tumor model. Hematoxylin and eosin staining was used to reveal the subcutaneous tumor tissue. The tumor volume and tumor weight were measured, the expression levels of proliferation markers proliferating cell nuclear antigen (PCNA) and Ki-67 were detected by immunohistochemistry, and the expression levels of CA72-4 were measured by enzyme linked immunosorbent assay. RESULTS: Oldenlandia diffusa flavonoids inhibited proliferation of MKN-45 and AGS human gastric cancer cells, arrested the cell cycle in G1/S phase, induced accumulation of ROS in the process of apoptosis, and altered MMP. In addition, flavonoids increased Apaf-1, Cleaved-Caspase-3, and Bax, and decreased Cyclin A, Cdk2, Bcl-2, Pro-Caspase-9, and Mitochondrial Cytochrome C (P<0.05). The MKN-45 cell mouse xenotransplantation model further clarified the growth inhibitory effect of flavonoids towards tumors. The expression levels of PCNA and Ki-67 decreased in each flavonoid dose group, the expression level of CA72-4 decreased (P<0.05). CONCLUSION: Flavonoids derived from Oldenlandia diffusa can inhibit proliferation and induce apoptosis of human gastric cancer cells by activating the mitochondrial controlled signal transduction pathway.

Response of microbial community structure to chromium contamination in Panax ginseng-growing soil.

Chromium (Cr) contamination in soil poses a serious security risk for the development of medicine and food with ginseng as the raw material. Microbiome are critical players in the functioning and service of soil ecosystems, but their feedback to Cr-contaminated ginseng growth is still poorly understood. To study this hypothesis, we evaluated the effects of microbiome and different Cr exposure on the soil microbial community using Illumina HiSeq high-throughput sequencing. Our results indicated that 2467 OTUs and 1785 OTUs were obtained in 16S and ITS1 based on 97% sequence similarity, respectively. Bacterial and fungal diversity were affected significantly in Cr-contaminated soil. Besides, Cr contamination significantly changed the composition of the soil bacterial and fungal communities, and some biomarkers were identified in the different classification level of the different Cr-contaminated treatments using LEfSe. Finally, a heatmap of Spearman's rank correlation coefficients and canonical discriminant analysis (CDA) indicated that Chloroflexi, Gemmatimonadetes, Acidobacteria, Verrucomicobia, and Parcubacteria in phylum level and Acidimicrobiia, Gemmatimonadetes, and Deltaproteobacteria in class level were positively correlated with AK, AP, and NO3--N (p < 0.05 or p < 0.01), but negatively correlated with total Cr and available Cr (p < 0.05 or p < 0.01). Similarly, in the fungal community, Tubaria, Mortierellaceae, and Rhizophagus in the phylum level and Glomeromycetes, Agaricomycetes, and Exobasidiomycetes in the class level were positively correlated with AK, AP, and NO3--N (p < 0.05 or p < 0.01), but negatively correlated with total Cr and available Cr (p < 0.05 or p < 0.01). Our findings provide new insight into the effects of Cr contamination on the microbial communities in ginseng-growing soil.

Effects of cadmium contamination on bacterial and fungal communities in Panax ginseng-growing soil.

BACKGROUND: Cadmium (Cd) contamination in soil poses a serious safety risk for the development of medicine and food with ginseng as the raw material. Microorganisms are key players in the functioning and service of soil ecosystems, but the effects of Cd-contaminated ginseng growth on these microorganisms is still poorly understood. To study this hypothesis, we evaluated the effects of microorganisms and Cd (0, 0.25, 0.5, 1.0, 2.0, 5.0, and 10.0 mg kg-1 of Cd) exposure on the soil microbial community using Illumina HiSeq high-throughput sequencing. RESULTS: Our results indicated that Cd-contaminated soil affected the soil microbial diversity and composition, and bacterial diversity was affected more than fungal diversity in Cd-contaminated soil, especially according to Shannon indices. The abundance of the soil microbial community decreased and the composition changed according to the relative abundances at the phylum level, including those of Saccharibacteria and Gemmatimonadetes in bacteria and Mortierellomycota in fungi. The LEfSe algorithm was used to identify active biomarkers, and 45 differentially abundant bacterial taxonomic clades and 16 differentially abundant fungal taxonomic clades were identified with LDA scores higher than 4.0. Finally, a heatmap of Spearman's rank correlation coefficients and canonical discriminant analysis (CDA) indicated that some key biomarkers, Arenimonas, Xanthomonadales, Nitrosomonadaceae, Methylophilales, Caulobacterales, Aeromicrobium, Chitinophagaceae, Acidimicrobiales, Nocardioidaceae, Propionibacteriales, Frankiales, and Gemmatimonadaceae, were positively correlated with the total and available Cd (p<0.05) but negatively correlated with AK, AP, and pH (p<0.05) in the bacterial community. Similarly, in the fungal community, Tubaria, Mortierellaceae, and Rhizophagus were positively correlated with the total and available Cd but negatively correlated with AK, AP, TK, and pH. CONCLUSION: Cd contamination significantly affected microbial diversity and composition in ginseng-growing soil. Our findings provide new insight into the effects of Cd contamination on the microbial communities in ginseng-growing soil.

[Response of root morphogenesis of medicinal plants to low phosphorus stress and molecular mechanism].

The content of available phosphorus in soil is generally low worldwide. Phosphorus, one of the necessary macroelements for plant growth and development, plays an important role in cell structure, material composition and energy metabolism, and signal transduction in plants. Phosphate transporter(PHT) genes are important for plant growth and development, root morphogenesis, secondary metabolism, hormone response, and phosphorus balance. Most of the active components in medicinal plants are secondary metabolites. Thus, it is essential to reveal the relationship between the regulation of phosphorus and the accumulation of active components in medicinal plants, especially the effect of phosphorus starvation on root morphogenesis of root medicinal materials and its coupling with hormone response. With advancement of molecular biology, scholars gradually emphasize the mechanism of PHT regulating the secondary metabolism of medicinal plants. This study summarized the strategies of plants to adapt to low phosphorus environment, such as changing root morphogenesis, inhibiting taproot growth, forming cluster root and changing physiological metabolism, PHT, its regulatory network, phenotypic biological characteristics and key genes in medicinal plants related to phosphorus starvation, and the response mechanism. The findings are expected to lay a basis for the cultivation of medicinal plants with high quality, excellent shape, and high price.

Mechanism of Xueniao Capsule in Treatment of Acute Pyelonephritis Based on Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Xueniao capsule in the treatment of acute pyelonephritis （APN） by network pharmacology and experimental verification. MethodThe effect of Xueniao capsule on APN was investigated based on the APN model in rats. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Chemistryl Database， and SymMap were searched for the chemical components of Smilacis Chinae Rhizoma，Coicis Semen， and Trachycarpi Petiolus. The target information of the components was collected from PharmMapper and SwissTargetPrediction， and disease target information from Therapeutic Target Database （TTD）， DrugBank， DisGeNET， GeneCards， and Online Mendelian Inheritance in Man（OMIM）. The key genes of Xueniao capsule for APN underwent Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analyses by Metascap. Real-time quantitative polymerase chain reaction （PCR） and Western blot were employed to verify the prediction results. ResultCompared with the blank group and the sham operation group， the model group showed an increased ratio of the left kidney to the right kidney and organ index（P<0.05， P<0.01），up-regulated white blood cells （WBC），neutrophils （NEUT），monocytes （MONO）， and lymphocytes （LY）（P<0.05， P<0.01）， and elevated levels of nuclear factor-κB（NF-κB）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α）（P<0.05， P<0.01）. Compared with the model group， the norfloxacin group， the low- and high-dose Xueniao capsule groups showed a decreased ratio of the left kidney to the right kidney and organ index（P<0.05， P<0.01）， dwindled levels of WBC， NEUT， MONO， and LY（P<0.05， P<0.01）， and reduced levels of NF-κB， IL-6， and TNF-α（P<0.05， P<0.01）. The medium-dose Xueniao capsule group showed a decreased ratio of the left kidney to the right kidney and organ index（P<0.05， P<0.01）， reduced levels of WBC， NEUT， MONO， and LY（P<0.05， P<0.01）， and dwindled levels of IL-6 and TNF-α（P<0.05， P<0.01）. Network pharmacological analysis revealed 17 active compounds from Smilacis Chinae Rhizoma， 18 active compounds from Coicis Semen， six active compounds from Trachycarpi Petiolus， and 39 key genes for the treatment of APN in Xueniao capsule. GO enrichment analysis demonstrated 704 biological processes， 22 cellular components， and 59 molecular functions. Sixty-two pathways were enriched in KEGG enrichment analysis. The experimental verification results showed that compared with the blank group， the model group showed increased mRNA expression of prostaglandin-endoperoxide synthase 2 （PTGS2）， mitogen-activated protein kinase 1 （MAPK1）/extracellular signal-regulated protein kinase 2 （ERK2），phosphoinositide 3 kinase （PI3K），protein kinase B2（Akt2），Janus kinase 2 （JAK2），and signal transducer and activator of transcription 3 （STAT3）and protein expression of PI3K， Akt2， JAK2， and STAT3 （P<0.05， P<0.01）. Compared with the model group， the low-dose Xueniao capsule group showed decreased mRNA expression of MAPK1， PI3K， JAK2， and STAT3 and protein expression of PI3K， JAK2， and STAT3 （P<0.05， P<0.01）. The medium-dose Xueniao capsule group showed decreased mRNA expression of MAPK1， PTGS2， PI3K， JAK2， and STAT3， and protein expression of PI3K， JAK2， and STAT3 （P<0.05， P<0.01）. The high-dose Xueniao capsule group showed reduced mRNA expression of PTGS2， MAPK1， PI3K， Akt2， JAK2， and STAT3 and protein expression of PI3K， Akt2， JAK2， and STAT3 （P<0.05， P<0.01）. ConclusionXueniao capsule has a certain curative effect on APN via multiple targets and multiple pathways. The mechanism may be related to the inhibition of the PI3K/Akt signaling pathway and the JAK2/STAT3 signaling pathway.

Sleep-improving mechanism of Chaiqin Ningshen Granules in insomnia rats: based on hippocampal metabonomics / 中国中药杂志

With the ultra high performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-MS)-based metabonomics technology, this study aims to analyze the effect of Chaiqin Ningshen Granules(CNG) on endogenous metabolites in insomnia rats of liver depression syndrome and explore the sleep-improving mechanism of this prescription. Parachlorophenylalanine(PCPA, ip) and chronic stimulation were combined to induce insomnia of liver depression pattern in rats, and the effect of CNG on the macroscopic signs, hemorheology, and neurotransmitters in the hippocampus of insomnia rats of liver depression syndrome was observed. After the administration, rat hippocampus was collected for liquid chromatography-mass spectrometry(LC-MS) analysis of the metabolomics. Principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed for analyzing the metabolites in rat hippocampus and screening potential biomarkers. MetPA was used to yield the related metabolic pathways and metabolic networks. The results show that the drugs can significantly improve the mental state, liver depression, and blood stasis of rats, significantly increase the content of 5-hydroxytryptamine(5-HT) and gamma aminobutyric acid(GABA) in hippocampus(except low-dose CNG), and significantly reduce the content of glucose(Glu)(except low-dose CNG). Among them, estazolam and high-dose CNG had better effect than others. Metabolomics analysis yielded 27 potential biomarkers related to insomnia. MetPA analysis showed 4 metabolic pathways of estazolam in intervening insomnia and 3 metabolic pathways of high-dose CNG in intervening insomnia, involving purine metabolism, glycerophospholipid metabolism, histidine metabolism, and caffeine metabolism. CNG can alleviate insomnia by regulating endogenous differential metabolites and further related metabolic pathways. The result lays a basis for further elucidating the mechanism of CNG in improving sleep.

Evaluation of origanum oil, hydrolysable tannins and tea saponin in mitigating ruminant methane: In vitro and in vivo methods.

The objective of this study was to investigate the effects of origanum oil (ORO), hydrolysable tannins (HYT) and tea saponin (TES) on methane (CH4 ) emission, rumen fermentation, productive performance and gas exchange in sheep by using in vitro and in vivo methods. The ORO, HYT and TES additive levels were normalized per kg dry matter (DM) in both in vitro and in vivo experiments: ORO-0, 10, 20 and 40 ml/kg; HYT-0, 15, 30 and 60 g/kg; and TES-0, 15, 30 and 60 g/kg, respectively. During in vitro incubation, 40 ml/kg ORO linearly decreased CH4 emission (p < 0.05); 20 and 40 ml/kg ORO cubically decreased carbon dioxide (CO2 ) production (p < 0.05), and rumen pH was cubically raised with the increasing ORO additive level (p < 0.01). The 60 g/kg HYT cubically decreased CH4 production (p < 0.05). The pH of 60 g/kg HYT was higher than that of 15 and 30 g/kg (p < 0.01); the pH of 20 g/kg TES was higher than that of 5 g/kg (p < 0.05). In the in vivo experiments, 40 ml/kg ORO inhibited dry matter intake (p < 0.01) cubically and reduced average daily gain (ADG) and feed conversion ratio (FCR) cubically (p < 0.05), and 20 or 40 ml/kg ORO linearly decreased CH4 production based on per day or metabolic weight (W0.75 ) (p < 0.05). Both 30 and 60 g/kg HYT linearly inhibited CH4 emission on the bases of per day and W0.75 (p < 0.05). The 20 g/kg TES improved the apparent digestibility of crude protein (p < 0.05), 10 and 20 g/kg of TES decreased CH4 emission (p < 0.05), and 5 g/kg of TES reduced O2 consumption and CO2 production (p < 0.05). In conclusion, these three plant extracts all showed the abilities on mitigating CH4 emission of sheep with appropriate additive ranges.

Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro.

COVID-19 has become a global pandemic and there is an urgent call for developing drugs against the virus (SARS-CoV-2). The 3C-like protease (3CLpro) of SARS-CoV-2 is a preferred target for broad spectrum anti-coronavirus drug discovery. We studied the anti-SARS-CoV-2 activity of S. baicalensis and its ingredients. We found that the ethanol extract of S. baicalensis and its major component, baicalein, inhibit SARS-CoV-2 3CLpro activity in vitro with IC50's of 8.52 µg/ml and 0.39 µM, respectively. Both of them inhibit the replication of SARS-CoV-2 in Vero cells with EC50's of 0.74 µg/ml and 2.9 µM, respectively. While baicalein is mainly active at the viral post-entry stage, the ethanol extract also inhibits viral entry. We further identified four baicalein analogues from other herbs that inhibit SARS-CoV-2 3CLpro activity at µM concentration. All the active compounds and the S. baicalensis extract also inhibit the SARS-CoV 3CLpro, demonstrating their potential as broad-spectrum anti-coronavirus drugs.

Effect of auricular point sticking therapy on perioperative pain in patients with partial lung resection / 中国针灸

OBJECTIVE@#To observe the analgesic effect of auricular point sticking therapy during the perioperative stage in the patients with partial lung resection.@*METHODS@#A total of 92 patients with partial lung resection were randomized into an auricular point group (31 cases, 1 case dropped off), the sham-auricular point group (30 cases) and a medication group (31 cases, 1 case dropped off). The routine medication for analgesia was provided in all of the three groups. In the auricular point group, 1 day before operation, the auricular point sticking therapy was applied at shenmen (TF@*RESULTS@#In 8, 16, 24, 48 h and 72 h after operation, VAS scores in the auricular point group were lower than those in the sham-auricular point group and the medication group separately (@*CONCLUSION@#Auricular point sticking therapy relieves perioperative pain, shortens analgesic time, releases anxious and depressive emotions and reduces postoperative adverse reaction in the patients with partial lung resection. The analgesic mechanism is probably related to the increase of plasma concentration of β-endorphin.

The effect of remote ischemic postconditioning on autonomic function in patients with acute ischemic stroke: A Randomized Controlled Trail.

OBJECTIVE: The evidence for the effect of remote ischemic postconditioning(RIpostC) on autonomic function in patients with acute ischemic stroke(AIS) is lacking and the neural mechanism underlying the protection of RIpostC remains speculative. This trial was aimed to evaluated the efficiency of RIpostC on autonomic function in AIS patients. DESIGN: One hundred and six AIS patients were included in this prospective, randomized, placebo-controlled trial. Patients in intervention group (n = 57) received 4 cycles of alternating inflation (cuff inflation to 200 mmHg) and deflation for 5 min on healthy upper arm once a day for 30 days. The control group underwent a sham inflation and deflation cycles. Autonomic function was evaluated by heart rate variability (HRV). RESULTS: All HRV parameters except for the ratio of low frequency to high frequency (P = 0.101) increased significantly with time (P < 0.001) in the two groups. The value of standard deviation of all normal R-R intervals(SDNN) and high frequency at day7 and day30 and the value of the percent of difference between adjacent normal R-R intervals (pNN50) at day 30 in RIpostC group was significantly higher than that of the sham-RIpostC group(P < 0.05). A significant time-by-group interaction was observed in SDNN、pNN50、and high frequency over time between two groups (P < 0.05). CONCLUSIONS: 30-day RIpostC could improve autonomic function in AIS patients through the enhancement of the total autonomic nerve activity and vagus nerve activity. The mechanism of RIpostC mediating autonomic function needs to be further investigated.

Ascorbic acid promotes the reproductive function of porcine immature Sertoli cells through transcriptome reprogramming.

Vitamin C (ascorbic acid, AA) can regulate antioxidation and affect many cellular processes. However, the effect of AA on the reproduction of male animals remains less explored. Here, we showed that by supplementing exogenous AA to porcine immature Sertoli cells (iSCs), AA could promote the proliferation, suppress apoptosis, and decrease the global nucleic acid methylation (5 mC and m6A) levels of iSCs. After we profiled mRNA and long non-coding RNA (lncRNA) expression by transcriptome sequencing on iSCs (treated by 250 µM AA for 36 h), 1232 mRNAs and 937 lncRNAs were identified to be differentially expressed (DE). Gene enrichment analysis found multiple significantly enriched biological pathways, including oxidoreductase activity, cell proliferation and apoptosis, regulation of hormone level, regulation of catalytic activity, developmental process, ATP metabolism and reproductive process. Specifically, for the reproductive process, 49 up- and 36 down-regulated DE mRNAs (including highly expressed genes, such as Tfcp2l1, Hmgcs1, Mmp7, Fndc3a, and Zfp36l1) are involved. Moreover, AA supplementation could promote the secretion of anti-müllerian hormone, inhibin B and lactate, and enhance the activity of lactate dehydrogenase as well. Taken together, AA could promote the reproductive function of pig iSCs, potentially through reprogramming the global transcriptome, and elevating hormone secretion and metabolite production.

Single cell RNA-seq reveals molecular pathways altered by 7, 12-dimethylbenz[a]anthracene treatment on pig oocytes.

Oocytes of better quality and developmental competence are highly demanded, which is affected by many intrinsic and external factors, including environmental pollutants. We have previously demonstrated that 7, 12-dimethylbenz [a]anthracene (DMBA) reduces the developmental competence of porcine oocytes, by desynchronizing nuclear and ooplasmic maturation. However, the underlying molecular mechanism remains obscure. Here we performed single cell RNA-seq to study the transcriptome changes in DMBA-treated porcine MII oocytes, and identified 19 protein-coding genes and 156 novel long non-coding RNAs (lncRNAs) with abundance to be significantly different (P < 0.05), which enriched in signaling pathways such as glycosphingolipid biosynthesis, nicotine addiction, basal transcription factors and nucleotide excision repair. RT-qPCR on oocyte pools confirmed ornithine aminotransferase (Oat) and serine/arginine-rich splicing factor 4 (Srsf4) to be significantly up- and down-regulated, respectively (P < 0.05). Treating porcine COCs with MAPK and PLC pathway inhibitors suppressed DMBA's effects on increasing PB1 extrusion rate. In addition, DMBA co-incubation with 250 µM vitamin C derivative (l-ascorbic acid 2-phosphate sesquimagnesium salt hydrate, AA2P) and 100 µM co-enzyme Q10 (CoQ10) could significantly reduce the DMBA-induced high ROS level, and partially alleviate the DMBA-induced high PB1 rate, whereas the cleavage and blastocyst rates of parthenotes derived from treated mature oocytes remained to be low. Collectively, our findings indicate that single cell RNA-seq can help reveal the dynamics of molecular signaling pathways for porcine oocytes treated by DMBA, and supplement of anti-oxidative reagents could not sufficiently rescue DMBA-induced defects of porcine oocytes.

Siwu Paste protects bone marrow hematopoietic function in rats with blood deficiency syndrome by regulating TLR4/NF-κB/NLRP3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Siwu Paste (SWP) was recorded in the first national Pharmacopoeia of China, "Tai Ping Hui Min He Ji Ju Fang", it showed excellent effects in regulating all syndromes relevant to blood. AIM OF THE STUDY: This study aimed to investigate the protective effects of Siwu Paste (SWP) on bone marrow hematopoietic by using rats' model with blood deficiency syndrome induced by chemotherapy. MATERIALS AND METHODS: Animal model with blood deficiency syndrome was successfully established by evaluating their peripheral blood cell level and erythrocyte membrane energy metabolism enzyme activity. Serum hematopoietic cytokine levels were detected by using Enzyme-linked immunosorbent assay (ELISA). Hematoxylin-Eosin (HE) staining method was used to observe the pathological morphology of femur bone marrow, and the viability of BMSC was detected by Cell Counting Kit (CCK-8). Furthermore, the expression of toll-like receptor 4 (TLR4), nuclear transcription factor kB (NF-κB), and NOD-like receptor protein 3 (NLRP3) protein in femur bone marrow were detected by using Western-blotting and High-content cell imaging analysis system (HCA). RESULTS: Obtained results showed that SWP could significantly improve the status of anemia, regulate the expressions of serum hematopoietic cytokines, and protect bone marrow hematopoietic cells. Furthermore, the expressions of TLR4, NF-κB, and NLRP3 protein were inhibited in bone marrow hematopoietic cells. CONCLUSIONS: Siwu Paste (SWP) could recover the bone marrow hematopoietic functions in rats with blood deficiency syndrome. The therapeutic mechanism may be related to the regulation of serum hematopoietic cytokines, and inhibition of TLR4/NF-κB/NLRP3 signaling pathway.

Preparation of Poly(glycidyl methacrylate) (PGMA) and Amine Modified PGMA Adsorbents for Purification of Glucosinolates from Cruciferous Plants.

Glucosinolates (GLs) are of great interest for their potential as antioxidant and anticancer compounds. In this study, macroporous crosslinked copolymer adsorbents of poly (glycidyl methacrylate) (PGMA) and its amine (ethylenediamine, diethylamine, triethylamine)-modified derivatives were prepared and used to purify the GLS glucoerucin in a crude extract obtained from a cruciferous plant. These four adsorbents were evaluated by comparing their adsorption/desorption and decolorization performance for the purification of glucoerucin from crude plant extracts. According to the results, the strongly basic triethylamine modified PGMA (PGMA-III) adsorbent showed the best adsorption and desorption capacity of glucoerucin, and its adsorption data was a good fit to the Freundlich isotherm model and pseudo-second-order kinetics; the PGMA adsorbent gave the optimum decolorization performance. Furthermore, dynamic adsorption/desorption experiments were carried out to optimize the purification process. Two glass columns were serially connected and respectively wet-packed with PGMA and PGMA-III adsorbents so that glucoerucin could be decolorized and isolated from crude extracts in one process. Compared with KCl solution, aqueous ammonia was a preferable desorption solvent for the purification of glucoerucin and overcame the challenges of desalination efficiency, residual methanol and high operation costs. The results showed that after desorption with 10% aqueous ammonia, the purity of isolated glucoerucin was 74.39% with a recovery of 80.63%; after decolorization with PGMA adsorbent, the appearance of glucoerucin was improved and the purity increased by 11.30%. The process of using serially connected glass columns, wet-packed with PGMA and PGMA-III, may provide a simple, low-cost, and efficient method for the purification of GLs from cruciferous plants.

A peptide inhibitor of macrophage migration in atherosclerosis purified from the leech Whitmania pigra.

ETHNOPHARMACOLOGICAL RELEVANCE: Atherosclerosis has become a worldwide public health problem that seriously threatens human health. Leech is traditional Chinese medicine that can be utilized to treat cardiovascular disease. Based on the anti-atherosclerosis activity of leech hydrolysate, we separated and purified the leech peptide capable of inhibiting macrophage migration and studied the pathways of the anti-migration leech peptide. MATERIALS AND METHODS: The leech peptide capable of inhibiting macrophage migration that measured by cell migration assays from the leech Whitmania pigra was separated and purified by Q Sepharose FF strong alkaline anion exchange column chromatography, Superdex 30, Superdex peptide and G10 gel column chromatography. And the purity, molecular weight of the leech peptide was determined by high-performance liquid chromatography and high-resolution mass spectrometry. The pathways of anti-migration to macrophages of the leech peptide were studied by inhibitors, Western blotting and RT-PCR. RESULTS: We obtained a purified leech peptide with a sequence of EAGSAKELEGDPVAG from the leech Whitmania pigra. We also showed that the anti-migration to macrophages of the leech peptide was blocked by c-Jun N-terminal kinase (JNK) inhibitor and p38 mitogen-activated protein kinase (p38 MAPK) inhibitor. Moreover, the result of RT-PCR and Western blotting revealed that the leech peptide induced an increase in JNK, p38 phosphorylation and the transcription of mitogen-activated protein kinase kinase kinase 4 (MEKK4) and apoptosis signal-regulating kinase 2 (ASK2). These data indicated that the anti-migration to macrophages of the leech peptide occurred through JNK and p38 MAPK pathways. In addition, the results demonstrated that the leech peptide had no significant effect on the immunological activity of macrophages including phagocytic ability, lysozyme activity, and levels of expression of inflammatory factors. CONCLUSION: A sequence peptide was obtained from the hydrolysate of leech Whitmania pigra that inhibits macrophage migration.