Exosomes derived from diabetic serum accelerate the progression of osteoarthritis.

Diabetes mellitus (DM) has been demonstrated to accelerate the progression of osteoarthritis (OA) by largely unknown mechanisms. Studies have shown that DM dysfunctional adipocyte-derived exosomes play a crucial role in the pathogenesis of remote organ functions. The present study aimed to clarify whether and how diabetic adipocyte-derived exosomes mediate the pathological regulation of OA. We found that intraarticular injection of DM serum exosomes in the non-diabetic mice significantly exacerbated OA injury as evidenced by a rough and fractured cartilage surface as well as increased chondrocyte apoptosis, decreased mitochondrial membrane potential (△Ψ) and increased expression of cleaved caspase-3. Mechanistic investigation identified that miR-130b-3p was significantly increased in circulating exosomes derived from DM mice and exosomes derived from HG-treated normal adipocytes, and we demonstrated that transfection of miR-130b-3p mimics significantly exacerbated the mitochondrial function of chondrocytes. Our data also indicated that miR-130b-3p impaired the △Ψ, increased cleaved caspase-3 levels, and decreased the expression of 5'-adenosine monophosphate-activated protein kinase α1 (AMPKα1), Silent mating-type information regulation 2 homolog 1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) in chondrocytes. Pharmacologic activation of AMPKα1 using AICAR reversed the â–³Ψ and catabolic responses in chondrocytes transfected with miR-130b-3p mimics. Moreover, AICAR decreased the effects of miR-130b-3p mimics on chondrocytes transfected with SIRT1-siRNA or PGC-1α-siRNA. The current study demonstrated that adipocyte-derived exosomal miR-130b-3p under DM conditions suppresses mitochondrial function in chondrocytes through targeting the AMPKα1/SIRT1/PGC1-α pathway, thus exacerbating OA injury.

Full-length transcriptome profiling of Acanthopanax gracilistylus provides new insight into the kaurenoic acid biosynthesis pathway.

Acanthopanax gracilistylus is a deciduous plant in the family Araliaceae, which is commonly used in Chinese herbal medicine, as the root bark has functions of nourishing the liver and kidneys, removing dampness and expelling wind, and strengthening the bones and tendons. Kaurenoic acid (KA) is the main effective substance in the root bark of A. gracilistylus with strong anti-inflammatory effects. To elucidate the KA biosynthesis pathway, second-generation (DNA nanoball) and third-generation (Pacific Biosciences) sequencing were performed to analyze the transcriptomes of the A. gracilistylus leaves, roots, and stems. Among the total 505,880 isoforms, 408,954 were annotated by seven major databases. Sixty isoforms with complete open reading frames encoding 11 key enzymes involved in the KA biosynthesis pathway were identified. Correlation analysis between isoform expression and KA content identified a total of eight key genes. Six key enzyme genes involved in KA biosynthesis were validated by real-time quantitative polymerase chain reaction. Based on the sequence analysis, the spatial structure of ent-kaurene oxidase was modeled, which plays roles in the three continuous oxidations steps of KA biosynthesis. This study greatly enriches the transcriptome data of A. gracilistylus and facilitates further analysis of the function and regulation mechanism of key enzymes in the KA biosynthesis pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01436-7.

Comparative Genomic Analysis of a Methylorubrum rhodesianum MB200 Isolated from Biogas Digesters Provided New Insights into the Carbon Metabolism of Methylotrophic Bacteria.

Methylotrophic bacteria are widely distributed in nature and can be applied in bioconversion because of their ability to use one-carbon source. The aim of this study was to investigate the mechanism underlying utilization of high methanol content and other carbon sources by Methylorubrum rhodesianum strain MB200 via comparative genomics and analysis of carbon metabolism pathway. The genomic analysis revealed that the strain MB200 had a genome size of 5.7 Mb and two plasmids. Its genome was presented and compared with that of the 25 fully sequenced strains of Methylobacterium genus. Comparative genomics revealed that the Methylorubrum strains had closer collinearity, more shared orthogroups, and more conservative MDH cluster. The transcriptome analysis of the strain MB200 in the presence of various carbon sources revealed that a battery of genes was involved in the methanol metabolism. These genes are involved in the following functions: carbon fixation, electron transfer chain, ATP energy release, and resistance to oxidation. Particularly, the central carbon metabolism pathway of the strain MB200 was reconstructed to reflect the possible reality of the carbon metabolism, including ethanol metabolism. Partial propionate metabolism involved in ethyl malonyl-CoA (EMC) pathway might help to relieve the restriction of the serine cycle. In addition, the glycine cleavage system (GCS) was observed to participate in the central carbon metabolism pathway. The study revealed the coordination of several metabolic pathways, where various carbon sources could induce associated metabolic pathways. To the best of our knowledge, this is the first study providing a more comprehensive understanding of the central carbon metabolism in Methylorubrum. This study provided a reference for potential synthetic and industrial applications of this genus and its use as chassis cells.

Advanced Glycation End Products Induced Mitochondrial Dysfunction of Chondrocytes through Repression of AMPKα-SIRT1-PGC-1α Pathway.

INTRODUCTION: Our previous studies have demonstrated advanced glycation end products (AGEs) was an important mediator in osteoarthritis (OA) which may induce mitochondrial dysfunction. AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and its downstream target peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) are the critical sensors that regulate mitochondrial biogenesis and have been recognized as therapeutic targets in OA. This study was designed to test whether AGEs caused mitochondrial dysfunction through modulation of AMPKα/SIRT1/PGC-1α. METHODS: We knocked down or overexpressed AMPKα, SIRT1, and PGC-1α by small interfering RNA or plasmid DNA transfection, respectively. Mitochondrial membrane potential (△Ψ) was detected by tetraethylbenzimidazolyl carbocyanine iodide (JC-1) fluorescence probe. RESULTS: The results showed that AGEs impaired △Ψ, intracellular ATP level, and mitochondrial DNA content, linked to decreased AMPKα, SIRT1, and PGC-1α expression in chondrocyte. AMPKα pharmacologic activation or overexpression of AMPKα, SIRT1, and PGC-1α reversed impairments of mitochondrial biogenesis, oxidative stress, and inflammation in AGEs-induced chondrocytes. However, AMPKα activation using AICAR had decreased capacity to increase each of those same effect readouts in AGEs-treated SIRT1-siRNA or PGC-1α-siRNA chondrocyte. CONCLUSION: Taken together, AGEs reduced the AMPKα/SIRT1/PGC-1α signaling in chondrocytes, leading to mitochondrial dysfunction as a result of increased oxidative stress, inflammation, and apoptosis. These results indicated that target AMPK may be as a novel therapeutic strategy for AGEs-related OA prevention.

Transcriptome analyses reveal the expression profile of genes related to lignan biosynthesis in Anthriscus sylvestris L. Hoffm. Gen.

Anthriscus sylvestris L. Hoffm. Gen (A. sylvestris) is a perennial herb widely used for antitussive and diuretic purposes in traditional Korean and Chinese medicine. Lignans are critical secondary metabolites with widely pharmacological activities in A. sylvestris. Using transcriptome data of A. sylvestris, we identified genes related to lignan biosynthesis. In all, 123,852 unigenes were obtained from the flowers, leaves, roots, and stems of A. sylvestris with the Illumina HiSeq 4000 platform. The average length of unigenes was 1,123 bp and 91,217 (73.65%) of them were annotated in public databases. Differentially expressed genes and root-specific genes were analyzed between roots and the other three tissue types by comparing gene expression profiles. Specifically, the key enzyme genes involved in lignan biosynthesis were identified and analyzed. The expression levels of some of these genes were highest in the roots, consistent with the accumulation of deoxypodophyllotoxin. These expression levels were experimentally verified via quantitative real-time polymerase chain reaction (qRT-PCR). This research provides valuable information on the transcriptome data of A. sylvestris and the identification of candidate genes associated with the biosynthesis of lignans, laying the foundation for further research on genomics in A. sylvestris and related species. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01156-w.

Eomes promotes esophageal carcinoma progression by recruiting Treg cells through the CCL20-CCR6 pathway.

Eomesodermin (Eomes) is a T-box transcription factor that drives the differentiation and function of cytotoxic lymphocytes. However, the underlying function and mechanism of Eomes in tumor cells remains elusive. Here, we studied the role of Eomes in human esophageal squamous cell carcinoma (ESCC). Using 2 human ESCC cell lines, we found that Eomes knockdown reduced esophageal cancer cell proliferation and that the esophageal cancer cell cycle was blocked in the G2/M phase. Mechanistically, we identified CCL20 as the main downstream target of Eomes. Furthermore, we found that CCL20 could chemoregulate regulatory T cells (Tregs) through their specific receptor CCR6, then promoting the proliferation of esophageal cancer cells. Eomes knockdown also delayed the growth of human ESCC xenografts in BALB/c nude mice. Importantly, in 133 human ESCC tissues, high Eomes levels were associated with poor clinical prognosis. Overall, our findings suggested that the Eomes-CCL20-CCR6 pathway plays a vital role in human ESCC progress. Therefore, targeting this pathway may represent a promising strategy for controlling human ESCC.

Murine pharmacokinetics and antimalarial pharmacodynamics of dihydroartemisinin trimer self-assembled nanoparticles.

Currently, conjugation of artemisinin-derived dimers, trimers, and tetramers is a viable strategy for developing new effective antimalarial candidates. Furthermore, nanotechnology is an effective means to achieve intravenous administration of hydrophobic drugs. In this paper, an ester-linked dihydroartemisinin trimer (DHA3) was synthesized and further prepared as self-assembled nanoparticles (DHA3NPs) by a one-step nanoprecipitation method. The pharmacokinetics and antimalarial pharmacodynamics of DHA3NPs were studied in rats and mice infected with Plasmodium yoelii BY265 (PyBY265). DHA3NPs had a regular spherical shape with a uniform size distribution of 140.27 ± 3.59 nm, entrapment efficiency (EE) of 99.63 ± 0.17%, and drug loading efficiency (DL) of 79.62 ± 0.11%. The in vitro release characterization revealed that DHA3NPs were easily hydrolysed into DHA in an esterase environment. The pharmacokinetics study demonstrated that the area under the concentration-time curve (AUC0-t) of DHA in DHA3NPs group was 2070.52 ± 578.76 h×ng×mL-1, which was higher than that of DHA and artesunate (AS) control groups (AUC0-t values of 724.18 ± 94.32 and 448.40 ± 94.45 h×ng×mL-1, respectively) (P < 0.05). The antimalarial pharmacodynamics in vivo suggested that DHA3NPS (ED90 7.82 ± 1.16 µmol×(kg×day)-1) had a superior antimalarial effect compared with that of control groups (ED90 values of 14.68 ± 0.98 (DHA) and 14.34 ± 1.96 (AS) µmol×(kg×day)-1) (P < 0.05). In addition, DHA3NPS reduced the recurrence ratio and improved the cure ratio and survival time. In summary, DHA3NPs exhibited promising pharmacokinetic characteristics and antimalarial pharmacodynamics in vivo.

Transcriptome analysis of Clinopodium gracile (Benth.) Matsum and identification of genes related to Triterpenoid Saponin biosynthesis.

BACKGROUND: Clinopodium gracile (Benth.) Matsum (C. gracile) is an annual herb with pharmacological properties effective in the treatment of various diseases, including hepatic carcinoma. Triterpenoid saponins are crucial bioactive compounds in C. gracile. However, the molecular understanding of the triterpenoid saponin biosynthesis pathway remains unclear. RESULTS: In this study, we performed RNA sequencing (RNA-Seq) analysis of the flowers, leaves, roots, and stems of C. gracile plants using the BGISEQ-500 platform. The assembly of transcripts from all four types of tissues generated 128,856 unigenes, of which 99,020 were mapped to several public databases for functional annotation. Differentially expressed genes (DEGs) were identified via the comparison of gene expression levels between leaves and other tissues (flowers, roots, and stems). Multiple genes encoding pivotal enzymes, such as squalene synthase (SS), or transcription factors (TFs) related to triterpenoid saponin biosynthesis were identified and further analyzed. The expression levels of unigenes encoding important enzymes were verified by quantitative real-time PCR (qRT-PCR). Different chemical constituents of triterpenoid saponins were identified by Ultra-Performance Liquid Chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS). CONCLUSIONS: Our results greatly extend the public transcriptome dataset of C. gracile and provide valuable information for the identification of candidate genes involved in the biosynthesis of triterpenoid saponins and other important secondary metabolites.

In vivo antimalarial activity and pharmacokinetics of artelinic acid-choline derivative liposomes in rodents.

It is urgent to develop new antimalarial drugs with good therapeutic effects to address the emergence of drug resistance. Here, the artelinic acid-choline derivative (AD) was synthesized by dehydration reaction and esterification reaction, aimed to avoid the emergence of drug resistance by synergistic effect of artemisinins and choline derivative, which could compete with choline for rate-limiting enzymes in the phosphatidylcholine (PC) biosynthetic pathway. AD was formulated into liposomes (ADLs) by the thin-film hydration method. Efficacy of ADLs was evaluated by Peters 4-day suppression test. The suppression percentage against Plasmodium yoelii BY265 (PyBY265) in ADLs group was higher than those of positive control groups (dihydroartemisinin liposomes, P < 0.05) and other control groups (P ⩽ 0.05) at the doses of 4.4, 8.8, 17.6 µmol (kg·d)-1, respectively. The negative conversion fraction, recrudescence fraction and survival fraction of ADLs group were superior to other control groups. Pharmacokinetics in rats after intravenous injection suggested that ADLs exhibited higher exposure levels (indexed by area under concentration-time curve) than that of AD solution, artelinic acid liposomes or artelinic acid solution (P < 0.01). Taken together, ADLs exhibited promising antimalarial efficacy and pharmacokinetic characteristics.

Comprehensive Analysis of Competing Endogenous RNA (ceRNA) Network Based on RNAs Differentially Expressed in Lung Adenocarcinoma Using The Cancer Genome Atlas (TCGA) Database.

BACKGROUND The aim of this study was to explore a comprehensive analysis of the competing endogenous (ceRNA) network of lung adenocarcinoma and predict its regulatory mechanism and prognosis correlation based on The Cancer Genome Atlas (TCGA) database. MATERIAL AND METHODS The genes expression data from 535 lung adenocarcinoma cases and 59 normal tissue cases were acquired and downloaded from TCGA database, and differentially expressed messenger RNA (mRNA), long noncoding RNA (lncRNA) and microRNA (miRNA) were selected primarily by "edgeR" package in R software, which further constructs lncRNA-miRNA-mRNA ceRNA network. We then proceed to carry out Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Kaplan-Meier survival analysis of the mRNAs involved in the ceRNA network. RESULTS There are 3 mRNAs (ANLN, IGFBP1, and TFAP2A) in differentially expressed genes, 4 lncRNAs (AC015923.1, FGF12-AS2, LINC00211, and MED4-AS1), and 2 miRNAs (miR-31 and miR-490) associated with the prognostic of lung adenocarcinoma. Besides, LINC00461 and has-mir-139 as key nodes were found in the ceRNA network. Significantly, miR-31 shows the greatest prognostic value related to the adverse effect of the prognostic of lung adenocarcinoma (P<0.001). CONCLUSIONS By analyzing the expression data of lung adenocarcinoma in TCGA database, we found that 3 mRNAs, 4 lncRNAs, and 2 miRNAs were screened as potential prognostic factors for lung adenocarcinoma. In addition, LINC00461 and has-mir-139 are 2 important regulatory network nodes in lung adenocarcinoma ceRNA.

Long noncoding RNA LINC00483/microRNA-144 regulates radiosensitivity and epithelial-mesenchymal transition in lung adenocarcinoma by interacting with HOXA10.

Lung adenocarcinoma (LAD) is the leading cause of cancer death worldwide. Long noncoding RNAs (lncRNAs) have been shown to play an important regulatory role in cancer biology, including that of LAD. The aim of this experiment was to explore the interaction of LINC00483, microRNA-144 (miR-144), and homeobox A10 (HOXA10), and their effects on radio sensitivity and epithelial-mesenchymal transition (EMT) of LAD. Initially, microarray analysis was used to screen out miRNAs and lncRNAs, as well as the differentially expressed genes related to LAD. Following the screening process, the targeting relationship of LINC00483, miR-144, and that of miR-144 and HOXA10 was determined. Following that, the expression of LINC00483, miR-144, messenger RNA (mRNA), as well as protein expression of HOXA10, MMP-2, MMP-9, E-cadherin, vimentin, and N-cadherin that followed in cells was determined. Also, the effect of LINC00483 on cell migration and invasion ability, and cell tumorigenic ability was detected. LINC00483 and HOXA10 were found to be upregulated whereas miR-144 was downregulated in LAD. Silencing of LINC00483 could competitively bind to miR-144, thereby upregulating HOXA10. LINC00483 or HOXA10 silencing led to decreased HOXA10, MMP-2, MMP-9, vimentin, and N-cadherin but elevated miR-144 and E-cadherin. Moreover, after being transfected with silenced LINC00483, the cell proliferation, migration, and invasion were inhibited with enhanced radiosensitivity. Consequently, the data of the study indicates that interference of LINC00483 weakens its competitive binding ability to miR-144, thus reducing HOXA10 expression, and enhancing radiosensitivity in LAD.

[Cloning and characterization of chalcone synthase and chalcone isomerase genes in Arisaema heterophyllum].

Chalcone synthase( CHS) and chalcone isomerase( CHI) are key enzymes in the biosynthesis pathway of flavonoids. In this study,unigenes for CHS and CHI were screened from the transcriptome database of Arisaema heterophyllum. The open reading frame( ORFs) of chalcone synthase( Ah CHS) and chalcone isomerase( Ah CHI) were cloned from the plant by RT-PCR. The physicochemical properties,expression and structure characteristics of the encoded proteins Ah CHS and Ah CHI were analyzed. The ORFs of Ah CHS and Ah CHI were 1 176,630 bp in length and encoded 392,209 amino acids,respectively. Ah CHS functioned as a symmetric homodimer. The N-terminal helix of one monomer entwined with the corresponding helix of another monomer. Each CHS monomer consisted of two structural domains. In particular,four conserved residues define the active site. The tertiary structure of Ah CHI revealed a novel open-faced ß-sandwich fold. A large ß-sheet( ß4-ß11) and a layer of α-helices( α1-α7) comprised the core structure. The residues spanning ß4,ß5,α4,and α6 in the three-dimensional structure were conserved among CHIs from different species. Notably,these structural elements formed the active site on the protein surface,and the topology of the active-site cleft defined the stereochemistry of the cyclization reaction. The homology comparison showed that Ah CHS had the highest similarity to the CHS of Anthurium andraeanum,while Ah CHI had the highest similarity to the CHI of Paeonia delavayi. This study provided the basis for the functional study of Ah CHS and Ah CHI and the further study on plant flavonoid biosynthesis pathway.

[Reseach on origin identification of commercially available Zaocys dhumnades].

Through market investigation, the adulteration of Zaocys dhumnades on markets was found out, and samples of authentic and adulterated Z. dhumnades on markets were collected. The origin and properties of the adulterated Z. dhumnades were studied in order to provide reference for the identification of Z. dhumnades. The counterfeit Z. dhumnades sold on markets were as follows: Ptyas korros, P. mucosus, Najanaja atra, Sinonatrix annularis, Dinodon septentrionalis, etc. It is found that there existed a obvious difference between the traits of the Z. dhumnades and counterfeits. Genuine Z. dhumnades with "sword ridge" "iron tail", strongly ribbed scales and other features, is the key point to identify the difference from adulterants.

Downregulated expression of microRNA-329 inhibits apoptosis of nigral dopaminergic neurons by regulating CDKN2D expression via the FoxO3a signaling pathway in rats with Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder due to the loss of dopaminergic neurons in the substantia nigra. This study focuses on the effect of microRNA-329 (miR-329) on nigral dopaminergic neurons in a rat model of PD via the FoxO3a signaling pathway by binding to CDKN2D. Brain tissues from the substantia nigra were taken from the rats in two groups. TUNEL staining was used to observe tyrosine hydroxylase (TH)-positive neurons. Nigral dopaminergic neurons were randomized into the normal, blank, negative control (NC), miR-329 mimics, miR-329 inhibitors, small interfering (siRNA)-CDKN2D, and miR-329 inhibitors + siRNA-CDKN2D groups. Expressions of miR-329, CDKN2D, FoxO3a, AKT, caspase-3 and Bcl-2 were determined using RT-qPCR and western blotting. Apoptosis rate of nigral dopaminergic neurons in 7 groups was determined by flow cytometry. Compared with the blank and NC groups, the miR-329 mimics group showed increased miR-329 and caspase-3 expressions as well as decreased expressions of CDKN2D, FoxO3a, AKT, and Bcl-2, the siRNA-CDKN2D group indicated enhanced expressions of caspase-3 and declined expressions of CDKN2D, FoxO3a, AKT, and Bcl-2, and the miR-329 inhibitors group revealed decreased miR-329 and caspase-3 expressions and increased expressions of CDKN2D, FoxO3a, AKT, and Bcl-2. The apoptosis rate of nigral dopaminergic neurons was significantly increased in the miR-329 mimics and siRNA-CDKN2D groups, but was decreased in the miR-329 inhibitors group. Our data suggested that downregulated miR-329 could inhibit apoptosis of nigral dopaminergic neurons in a rat model of PD by upregulating the expression of CDKN2D via the activation of the FoxO3a signaling pathway.

Up-Regulation of MicroRNA-133a Inhibits the MEK/ERK Signaling Pathway to Promote Cell Apoptosis and Enhance Radio-Sensitivity by Targeting EGFR in Esophageal Cancer In Vivo and In Vitro.

This study aims to explore how microRNA-133a (miR-133a) affects cell apoptosis and radio-sensitivity by targeting EGFR via regulating MEK/ERK pathway in esophageal cancer (EC). A total of 358 EC patients were selected and assigned into the resistant and sensitive groups. Human EC KYSE 150 cell line was assigned into the blank, negative control (NC), miR-133a mimic, miR-133a inhibitors, si-EGFR, miR-133a inhibitors + si-EGFR groups after transfection. MiR-133a and EGFR mRNA expressions were detected by qRT-PCR and EGFR, MEK/ERK pathway-related protein expressions were detected by Western blotting. The radio-sensitivity and cell apoptosis were testified by clone formation and flow cytometry. MiR-133a was up-regulated but EGFR was down-regulated in the sensitive group than in the resistant group. Compared with the blank and NC groups, the miR-133a mimic and si-EGFR groups exhibited increased cell apoptosis rate but decreased EGFR, p-MEK1/2, and p-ERK1/2 protein expressions; while opposite trend was observed in the miR-133a inhibitors group. Compared with the miR-133a inhibitors group, the miR-133a inhibitors + si-EGFR group presented reduced cell survival rate, EGFR, p-MEK1/2, and p-ERK1/2 protein expressions but increased cell apoptosis rate. These results indicated that miR-133a could inhibit the MEK/ERK pathway to promote cell apoptosis and enhance radio-sensitivity by targeting EGFR in EC. J. Cell. Biochem. 118: 2625-2634, 2017. © 2017 Wiley Periodicals, Inc.

Nepetaefolins A-J, Cytotoxic Chinane and Abietane Diterpenoids from Caryopteris nepetaefolia.

Nepetaefolins A-J (1-10) and seven known compounds were isolated from the whole plant of Caryopteris nepetaefolia. The absolute configurations of 1-3 were determined from single-crystal X-ray diffraction and spectroscopic data. Compounds 6 and 7, with IC50 values of 6.3-9.0 µM, showed higher cytotoxicity than paclitaxel in one non-small-cell lung cancer, patient-derived xenograft (PDX) model when tested using PDX models and the adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA).

[Chemical constituents from fresh tubers of Dioscorea bulbifera].

Eighteen compounds were isolated from the 95% ethanol extract of fresh tubers of Dioscorea bulbifera by column chromatography over silica gel,Sephadex LH-20, and ODS. Their structures were elucidated by spectroscopic data analysis as 6-hydroxy-2,10,10-trimethoxy-anthracen-9-one(1), diosgenin (2), stigmasterol(3), 3, 7-dimethoxy-5, 3', 4'-trihydroxyflavone(4), 2, 7-dihydroxy-3, 4-dimethoxyphenanthrene(5), 3, 7-dihydroxy-2, 4-dimethoxy phenanthrene(6), 2, 7-dihydroxy-4-methoxyphenanthrene (7), 2, 7-dihydroxy-3, 4-dimethoxy-9, 10-dihydroxy phenanthrene(8), azelaic acid (9), 8-epidiosbulbin E acetate (10), 1, 7-bis-(4-hydroxyphenyl)-4E, 6E-heptadien-3-one(11), diosbulbin B(12), pentacosanoic acid 2', 3'-dihydroxypropyl ester(13), 2, 7-dihydroxy-4-methoxy-9, 10-dihydroxy-phenanthrene (14), 1, 7-bis-(4-hydroxyphenyl)-1E, 4E, 6E-heptatrien-3-one (15), 6-ethoxy-1H-pyrimidine-2, 4-dione (16), 3, 5, 4'-trihydroxy-bibenzyl (17), and diosbulbin F (18). Compound 1 is a new compound, and compounds 7, 9, 13, and 16 were isolated from this plant for the first time.

[Evolution and transition of source of Patrinia Herba and Patrinia Radix].

Both Patrinia Herba and Patrinia Radix are traditional Chinese herbal medicines. The herbal source and medicinal part of them are confusing in the herbal medicine market of China. To explore the evolution and transition of the herbal source and medicinal part of Patrinia Herba and Patrinia Radix, this paper systematically summarizes the record of the herbal source and medicinal part of them in ancient classics of herbal medicine in China. According to the findings, before Ming Dynasty, Patrinia Herba originated from the radix of the plants with yellow flowers of Patrinia. In Ming and Qing Dynasty, Patrinia Herba originates from the whole plant (including the radix)of the plant with white flowers of Patrinia. In Ming Dynasty, Patrinia Radix, stemming from the radix of the plants with yellow flowers of Patrinia, started to be used as a traditional Chinese herbal medicine, which had the same herbal source with that of Patrinia Herba before Ming Dynasty. Therefore, Patrinia Herba and Patrinia Radix can be seen as the same traditional Chinese herbal medicine, and the genuine of Patrinia Herba should be the radix and the whole herba of P. scabiosaefolia and P. heterophylla.

Involvement of microRNA-135a-5p in the Protective Effects of Hydrogen Sulfide Against Parkinson's Disease.

BACKGROUND/AIMS: Development of effective therapeutic drugs for Parkinson's disease is in great need. During the progression of Parkinson's disease, Rho-associated protein kinase 2 (ROCK2) is activated to promote neurodegeneration. Hydrogen sulfide (H2S) has a neuroprotective effect during the neural injury of Parkinson's disease. However, the mechanisms that underlie the effects of ROCK2 and H2S remain ill-defined. In the current study, we addressed these questions. METHODS: We used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse subacute model of Parkinson's disease to study the effects of H2S on astrocytic activation in the mouse striatum, on the levels of tyrosine-hydroxylase (TH)-positive neuron loss, on the apomorphine-induced rotational behavior of the mice, and on the changes in ROCK2 and miR-135a-5p expression. Plasmid transfection was applied to modify miR-135a-5p levels in a neuronal cell line HCN-1A. Bioinformatics analysis was performed to predict the relationship between ROCK2 and miR-135a-5p in neuronal cells, and then was confirmed by luciferase reporter assay. RESULTS: H2S alleviated MPTP-induced astrocytic activation in the mouse striatum, alleviated the increases in TH-positive neuron loss, and improved the apomorphine-induced rotational behavior of the mice. H2S significantly attenuated the increases in ROCK2 and the decreases in miR-135a-5p by MPTP. MiR-135a-5p targeted the 3'-UTR of ROCK2 mRNA to inhibit its translation in neuronal cells. CONCLUSION: MiR-135a-5p-regulated ROCK2 may play a role in the protective effects of hydrogen sulfide against Parkinson's disease.

Abietane diterpenoids from Caryopteris incana (Thunb.) Miq.

Twelve new diterpenes, caryopincaolide A-L (1-4, 11-12, 16-19, 27-28), together with twenty-eight known diterpenes, have been isolated from the whole plant of Caryopteris incana (Thunb.) Miq. Their structures were elucidated on the basis of 1D and 2D NMR, IR, X-ray crystal diffraction and mass spectroscopic data, as well as ECD calculations. All compounds were tested for in vitro dipeptidyl peptidase IV (DPP-IV) inhibitory activity, with compounds 3, 4, 28, 29, and 40 exhibiting DPP-IV inhibitory effects with IC50 values ranging from 54.2 to 228.9 µM. Compounds 1, 3 and 4 also showed potent activity toward the inhibition of the growth of human cancer cells and 1 can induce apoptosis in Hey and A-549 cells.