Iridoids modulate inflammation in diabetic kidney disease: A review.

In recent years, preclinical research on diabetic kidney disease (DKD) has surged to the forefront of scientific and clinical attention. DKD has become a pervasive complication of type 2 diabetes. Given the complexity of its etiology and pathological mechanisms, current interventions, including drugs, dietary modifications, exercise, hypoglycemic treatments and lipid-lowering methods, often fall short in achieving desired therapeutic outcomes. Iridoids, primarily derived from the potent components of traditional herbs, have been the subject of long-standing research. Preclinical data suggest that iridoids possess notable renal protective properties; however, there has been no summary of the research on their efficacy in the management and treatment of DKD. This article consolidates findings from in vivo and in vitro research on iridoids in the context of DKD and highlights their shared anti-inflammatory activities in treating this condition. Additionally, it explores how certain iridoid components modify their chemical structures through the regulation of intestinal flora, potentially bolstering their therapeutic effects. This review provides a focused examination of the mechanisms through which iridoids may prevent or treat DKD, offering valuable insights for future research endeavors. Please cite this article as: Zhou TY, Tian N, Li L, Yu R. Iridoids modulate inflammation in diabetic kidney disease: A review. J Integr Med. 2024; 22(3): 210-222.

High-dose Vitamin C injection ameliorates against sepsis-induced myocardial injury by anti-apoptosis, anti-inflammatory and pro-autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR signaling pathways in rats.

AIMS: This study aimed to evaluate the effects of VC on SIMI in rats. METHODS: In this study, the survival rate of high dose VC for SIMI was evaluated within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and high dose VC (500 mg/kg i.v.) group. The animals in each group were treated with drugs for 1 day, 3 days or 5 days, respectively. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1ß, IL-6, IL-10 and TNF-α) in serum were measured using ELISA kits. Western blot was used to detect proteins related to apoptosis, inflammation, autophagy, MAPK, NF-κB and PI3K/Akt/mTOR signaling pathways. RESULTS: High dose VC improved the survival rate of SIMI within 7 days. Echocardiography, HE staining and myocardial enzymes showed that high-dose VC relieved SIMI in rats in a time-dependent manner. And compared with CLP group, high-dose VC decreased the expressions of pro-apoptotic proteins, while increased the expression of anti-apoptotic protein. And compared with CLP group, high dose VC decreased phosphorylation levels of Erk1/2, P38, JNK, NF-κB and IKK α/ß in SIMI rats. High dose VC increased the expression of the protein Beclin-1 and LC3-II/LC3-I ratio, whereas decreased the expression of P62 in SIMI rats. Finally, high dose VC attenuated phosphorylation of PI3K, AKT and mTOR compared with the CLP group. SIGNIFICANCE: Our results showed that high dose VC has a good protective effect on SIMI after continuous treatment, which may be mediated by inhibiting apoptosis and inflammatory, and promoting autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR pathway.

miR828a-CsMYB114 Module Negatively Regulates the Biosynthesis of Theobromine in Camellia sinensis.

Theobromine is an important quality component in tea plants (Camellia sinensis), which is produced from 7-methylxanthine by theobromine synthase (CsTbS), the key rate-limiting enzyme in theobromine biosynthetic pathway. Our transcriptomics and widely targeted metabolomics analyses suggested that CsMYB114 acted as a potential hub gene involved in the regulation of theobromine biosynthesis. The inhibition of CsMYB114 expression using antisense oligonucleotides (ASO) led to a 70.21% reduction of theobromine level in leaves of the tea plant, which verified the involvement of CsMYB114 in theobromine biosynthesis. Furthermore, we found that CsMYB114 was located in the nucleus of the cells and showed the characteristic of a transcription factor. The dual luciferase analysis, a yeast one-hybrid assay, and an electrophoretic mobility shift assay (EMSA) showed that CsMYB114 activated the transcription of CsTbS, through binding to CsTbS promoter. In addition, a microRNA, miR828a, was identified that directly cleaved the mRNA of CsMYB114. Therefore, we conclude that CsMYB114, as a transcription factor of CsTbS, promotes the production of theobromine, which is inhibited by miR828a through cleaving the mRNA of CsMYB114.

Calycosin enhances Treg differentiation for alleviating skin inflammation in atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder that poses a significant global health challenge. There is a lack of safe and effective medications to treat AD. Astragalus membranaceous is a traditional Chinese medicine widely used in clinical treatment of skin diseases. Calycosin (CA), derived from the root of Astragalus membranaceous, exhibits dual attributes of anti-inflammatory and antioxidant properties, suggesting its promise for addressing cutaneous inflammation. Nonetheless, the precise mechanisms underlying CA's therapeutic actions in AD remain elusive. AIM OF THE STUDY: This study aimed to evaluate the efficacy and safety of CA in treating AD while also delving into the mechanistic underpinnings of CA's action in AD. MATERIALS AND METHODS: The cell viability and anti-inflammatory impacts of CA in vitro were first gauged using CCK-8 and RT-qPCR. The potential mechanisms of CA were then probed using modular pharmacology. Flow cytometry was employed to ascertain the differentiation of Treg and Th17 cells derived from naïve T cells, as well as the proportions and mean fluorescence intensity (MFI) of human iTreg cells. The expressions of IL-10 and TGF-ß1 were measured and Treg suppression assay was performed. The in vivo therapeutic efficacy of topical CA application was assessed using a calcipotriol (MC903)-induced AD mouse model. The expression metrics of inflammatory cytokines, IL-17A, FOXP3, and RORγt were authenticated via immunohistochemistry, RT-qPCR, Western blot, and ELISA. RESULTS: CA exhibited a favorable safety profile and reduced the mRNA expressions of Th2 inflammatory cytokines in HaCaT cells. Modular pharmacology analysis pinpointed Th17 differentiation as the pivotal mechanism behind CA's therapeutic effect on AD. In vitro, CA fostered the differentiation of naïve T cells into Tregs while inhibiting their differentiation into Th17 cells. Furthermore, CA augmented the proliferation of human iTregs. In vivo, CA alleviated skin manifestations and decreased the levels of inflammatory mediators (IL-4, IL-5, IL-13, TSLP, and NF-κB related cytokines) in AD-like mouse models. Simultaneously, it regulated Treg/Th17 balance through suppressing IL-17A and RORγt expressions and bolstering FOXP3 expression. CONCLUSIONS: The study provides insights into the mechanistic pathways through which CA exerts its anti-inflammatory effects, particularly through promoting Treg cell differentiation and inhibiting Th17 cell differentiation. Furthermore, CA emerges as an alternative or adjunctive treatment strategy for managing AD.

Photothermal and Concus Finn capillary assisted superhydrophobic fibrous network enabling instant viscous oil transport for crude oil cleanup.

Rapid and effective removal of highly viscous oil spills from the sea remains a great challenge globally. Superhydrophobic materials are attractive candidates for handling oil spills, but they are restrained to recover oils with low viscosity exclusively. Herein, we report a novel polypyrrole wrapped superhydrophobic fibrous network using cross-shaped polyester fibers as starting blocks. The polypyrrole coating enables the absorbent to convert light to heat, ensuring that the viscosity of heavy oils in the proximity can be easily controlled. In the meanwhile, the special structure of the starting fibers initiates Concus Finn (CFin) capillary allowing instant oil transport in the network. When the absorbent is exposed to light oils (0-500 mPa.s), the oils can be transported instantly via CFin capillary. Interestingly, under synergistic effect of light-to-heat conversion and CFin capillary, a drawing-sticking crude oil strip (105 mPa.s) is sucked instantly against gravity by the absorbent. The absorbent is successfully applied to efficiently separate both oil/water mixtures and oil/water emulsions (efficiency > 99%). Such absorbent can absorb 62.99-74.23 g/g light oils on average and up to 123.3 g/g crude oil under 0-2 sun illumination, holding a huge potential in managing oil spills.

Comparative Transcriptome Analysis of Agrobacterium tumefaciens Reveals the Molecular Basis for the Recalcitrant Genetic Transformation of Camellia sinensis L.

Tea (Camellia sinensis L.), an important economic crop, is recalcitrant to Agrobacterium-mediated transformation (AMT), which has seriously hindered the progress of molecular research on this species. The mechanisms leading to low efficiency of AMT in tea plants, related to the morphology, growth, and gene expression of Agrobacterium tumefaciens during tea-leaf explant infection, were compared to AMT of Nicotiana benthamiana leaves in the present work. Scanning electron microscopy (SEM) images showed that tea leaves induced significant morphological aberrations on bacterial cells and affected pathogen-plant attachment, the initial step of a successful AMT. RNA sequencing and transcriptomic analysis on Agrobacterium at 0, 3 and 4 days after leaf post-inoculation resulted in 762, 1923 and 1656 differentially expressed genes (DEGs) between the tea group and the tobacco group, respectively. The expressions of genes involved in bacterial fundamental metabolic processes, ATP-binding cassette (ABC) transporters, two-component systems (TCSs), secretion systems, and quorum sensing (QS) systems were severely affected in response to the tea-leaf phylloplane. Collectively, these results suggest that compounds in tea leaves, especially gamma-aminobutyrate (GABA) and catechins, interfered with plant-pathogen attachment, essential minerals (iron and potassium) acquisition, and quorum quenching (QQ) induction, which may have been major contributing factors to hinder AMT efficiency of the tea plant.

Transcriptomics analysis reveals the signal transduction mechanism of brassinolides in tea leaves and its regulation on the growth and development of Camellia sinensis.

BACKGROUND: Brassinosteroids (BRs) are a type of sterol plant hormone that play an important role in various biochemical and physiological reactions such as promoting cell growth, increasing biomass, and improving stress resistance. RESULTS: To investigate the regulatory and molecular mechanism of BRs on the growth and development of tea plants (Camellia sinensis L.), changes in cell structure and gene expression levels of tea leaves treated with exogenous BRs were analyzed by electron microscopy and high-throughput Illumina RNA-Seq technology. The results showed that the number of starch granules in the chloroplasts and lipid globules increased and thylakoids expanded after BR treatment compared with the control. Transcriptome analysis showed that in the four BR treatments (CAA: BR treatment for 3 h, CAB: BR treatment for 9 h, CAC: BR treatment for 24 h, and CAD: BR treatment for 48 h), 3861 (1867 upregulated and 1994 downregulated), 5030 (2461 upregulated and 2569 downregulated), 1626 (815 upregulated and 811 downregulated), and 2050 (1004 upregulated and 1046 downregulated) differentially expressed genes were detected, respectively, compared with CAK (BR treatment for 0 h). Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, metabolic pathway enrichment analysis showed that the differentially expressed genes of CAA vs. CAK, CAB vs. CAK, CAC vs. CAK, and CAD vs. CAK significantly enriched the functional categories of signal transduction, cell cycle regulation, and starch, sucrose, and flavonoid biosynthesis and metabolism pathways. We also found that after spraying BR, the key genes for caffeine synthesis were downregulated. The results of qRT-PCR coincided with the findings of transcriptomic analysis. CONCLUSIONS: The present study improved our understanding of the effects of BRs on the growth and development of tea leaves and laid the foundation for the in-depth analysis of signal transduction pathways of BRs in tea leaves.

Development and Application of a Fast Gas Chromatographic Method Offer New Insights into l-theanine Production Regulation in Camellia sinensis L.

Tea is the most consumed beverage worldwide, and l-theanine in tea leaves significantly affects their flavor and market quality. We have developed and validated a fast and reliable gas chromatographic method with flame ionization detection (GC-FID) to quantify l-theanine after its extraction from Camellia sinensis (tea plant) and derivatization. The procedure was completed in 40 min, from extraction to chromatographic analysis, with a recovery rate of more than 93% and allowing a high sample throughput. The GC-FID intraday precision was within 0.57-2.28%, while the interday precision ranged from 1.57 to 13.48%. The intraday accuracy ranged from -6.84 to 5.26%, while the interday accuracy ranged from -1.08 to 3.12%. The limit of detection was 2.28 µg/mL, and the limit of quantification was 6.47 µg/mL. The GC-FID method was validated by high-performance liquid chromatography with UV detection (HPLC-UV) and was used to investigate the biosynthesis and regulation of l-theanine in tea plants. We found that plants fed with ethylamine significantly increased l-theanine concentrations in roots, while exogenous supplementation of glutamic acid, carbamide, and glutamine did not significantly affect the l-theanine level in roots. Our results also indicated that roots were not indispensable for the biosynthesis of l-theanine, which was detected in undifferentiated embryonic calluses in concentrations (g/100 g dry weight) as high as in leaves of whole plants (1.67 and 1.57%, respectively) and without any exogenous theanine precursor supplementation.

[Analysis of Water Quality and Exchange Flux of Interstitial Water-Overlying Water in Sediments of Baiyangdian Entrance Area in Summer].

In order to reveal the interaction of overlying water-interstitial water nitrogen and phosphorus nutrient salt in summer at the entrance region of Baiyangdian Lake, this study sampled six main rivers in the region during July 2019. An analysis of the overlying water and interstitial water quality characteristics and the diffusion flux of applied nutrients at the sediment-water interface revealed the effects of nutrient diffusion on sediments and overlying water. The overlying water analysis showed that the water quality was slightly alkaline in the Baiyangdian Lake. The content of dissolved oxygen (DO) was lower, which provided an anaerobic environment for the release of endogenous pollutants from sediments. The ammonia nitrogen (NH4+-N) ranged from 0.35 to 1.76 mg·L-1, and the content of ammonia nitrogen was the highest in the Zhulong River, which was the main source of water supply. The nitrate nitrogen (NO3--N) content ranged from 0.75 to 1.97 mg·L-1. The total dissolved nitrogen (TDN) ranged from 0.99 to 2.70 mg·L-1, and the content of TDN was the highest in Puhe River. The content of total dissolved phosphorus (TDP) was 0.03 to 0.15 mg·L-1, and the content of TDP was the highest was Baigouyin River, which is near the residential area. The results indicated that the content of ammonia nitrogen in the interstitial water was between 5.24 and 10.64 mg·L-1, which was 10 times that of the overlying water, and endogenous pollution in the former was severe. The nitrate nitrogen content ranged from 0.36 to 0.79 mg·L-1. The total dissolved nitrogen content was between 5.36 and 12.02 mg·L-1, which was 5 times higher than that of the overlying water. The total dissolved phosphorus was between 0.03 and 0.3 mg·L-1. According to integrated pollution index, the degree of interstitial water pollution was much higher than that of overlying water, and the sampling points are seriously polluted. The exchange flux analysis of NH4+-N, TDN, and TDP demonstrated that the diffusion flux of NH4+-N was between 1.71 and 7.43 mg·(m2·d)-1, and the diffusion rate of endogenous ammonia nitrogen to the overlying water was fastest in Fu River, the absorbing river in Baoding. The diffusion flux of total dissolved nitrogen was lower in the Baigouyin River, and the other five sample points averaged 9.11 mg·(m2·d)-1. In summer, the dissolved oxygen was lower and the water-sediment had a larger concentration difference, which led to massive nitrogen nutrient of sediment in anaerobic conditions released to the overlying water in great quantities that caused the serious pollution. The diffusion flux of dissolved total phosphorus showed that the sediment of Pinghe River acted as a "sink" of phosphorus nutrients, and the other sampling points ranged from 0.03 to 0.16 mg·(m2·d)-1, showing the state of phosphorus nutrient released upward to the overlying water. Finally, diffusion flux indicated that endogenous pollutants are crucial sources of overlying water pollutants. In order to effectively control the water quality in the entrance area, desilting the nitrogen and phosphorus nutrient salt of sediment is urgently required.

Recent advances in functionalized upconversion nanoparticles for light-activated tumor therapy.

Upconversion nanoparticles (UCNPs) are a class of optical nanocrystals doped with lanthanide ions that offer great promise for applications in controllable tumor therapy. In recent years, UCNPs have become an important tool for studying the treatment of various malignant and nonmalignant cutaneous diseases. UCNPs convert near-infrared (NIR) radiation into shorter-wavelength visible and ultraviolet (UV) radiation, which is much better than conventional UV activated tumor therapy as strong UV-light can be damaging to healthy surrounding tissue. Moreover, UV light generally does not penetrate deeply into the skin, an issue that UCNPs can now address. However, the current studies are still in the early stage of research, with a long way to go before clinical implementation. In this paper, we systematically analysed recent advances in light-activated tumor therapy using functionalized UCNPs. We summarized the purpose and mechanism of UCNP-based photodynamic therapy (PDT), gene therapy, immunotherapy, chemo-therapy and integrated therapy. We believe the creation of functional materials based on UCNPs will offer superior performance and enable innovative applications, increasing the scope and opportunities for cancer therapy in the future.

[Identification of Gastrodia elata and its hybrid by polymerase chain reaction].

Gastrodia elata is a kind of traditional Chinese medicinal materials and has good medicinal value. G. elata is divided into five varieties, which includes G. elata f. elata(proto variant), G. elata f. glauca, G. elata f. viridis, G. elata f. flavid and G. elata f. alba. Among them, G. elata f. elata and G. elata f. glauca have excellent characteristics and higher contents of gastrodin and polysaccharides. The hybrid of G. elata f. elata and G. elata f. glauca is present in markets, but the characteristics between hybrid and parent are not obvious and distinguished quickly and accurately. The aim of this study is to establish a PCR specific PCR identification method, which can identify G. elata f. elata, G. elata f. glauca and their hybrid. Based on the re-sequencing results of G. elata, we screened for the single nucleotide polymorphism(SNP) variation sites, and designed two pairs of specific primers(W291-F/W291-R and H255-F/H255-R). We further collected G. elata f. elata, G. elata f. glauca and their hybrid samples from different regions, established and optimized PCR method, and investigated and verified their tolerance and applicability. The results showed that when the annealing temperature was 48 ℃ and the number of cycles was 33, 255 bp specific band were obtained from G. elata f. glauca and hybrid by using specific primers W291-F/W291-R. When the annealing temperature was 51 ℃ and the number of cycles was 33, 291 bp specific band were obtained from G. elata f. elata and hybrid by using specific primers H255-F/H255-R. Our method could be used as a promising method to identify G. elata f. elata, G. elata f. glauca and their hybrid.

Anti-CD40 monoclonal antibody ameliorates experimental autoimmune uveoretinitis in mice.

OBJECTIVE: To investigate the effects of CD40 on ocular inflammation in experimental autoimmune uveoretinitis (EAU) in B10.RIII mice. ANIMALS STUDIED: EAU-susceptible B10.RIII mice were subcutaneously immunized with interphotoreceptor retinoid-binding protein (IRBP) 161-180 in complete Freund's adjuvant and evaluated clinically and pathologically on days 7, 14, 21, 28, and 35 postimmunization. Anti-CD40 antibody was intraperitoneally injected into mice every other day from days 7 to 14 postimmunization. Phosphate-buffered saline (PBS)-injected EAU mice were used as the controls. PROCEDURES: The frequencies of CD11c+ CD40+ dendritic cells (DCs), CD11c+ MHC-II+ DCs, and CD11c+ CD40+ MHC-II+ DCs in splenocytes were evaluated by flow cytometry on days 0, 7, 14, and 21 after immunization. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 production in CD11c+ DCs was assessed by ELISA. IRBP-specific lymphocyte proliferation was assessed using a modified MTT cell proliferation assay. RESULTS: The number of CD11c+ CD40+ DCs, CD11c+ MHC-II+ DCs, and CD11c+ CD40+ MHC-II+ DCs increased at the onset of EAU, peaked at the height of disease severity, and was sustained at a high level until day 21. Treatment with anti-CD40 antibody significantly alleviated clinical and pathological activities related to EAU. Compared with the control mice, antibody-treated EAU mice showed few CD11c+ CD40+ DC and CD11c+ CD40+ MHC-II+ DC frequencies in splenocytes. The anti-CD40 antibody significantly suppressed IRBP-specific lymphocyte proliferation and TNF-α and IL-6 production by DCs in EAU mice. CONCLUSIONS: The increased expression of CD40 and major histocompatibility complex (MHC) class II molecules in the splenocytes of EAU mice were correlated with inflammatory activity. Anti-CD40 treatment can significantly attenuate EAU activity by inhibiting systemic IRBP-specific immune responses.

[DNA fingerprinting identification of bile power(bile)medicines].

The pig bile powder, bovine bile powder, snake bile, sheep bile, goose bile powder, and bear bile powder were contained by the Chinese Pharmacopoeia. The bile power medicine has a long history in traditional Chinese medicine and definite effect. However, the medicine of bile powder(bile) are similar in morphology. Besides, many medicine lack specific microscopic identification characteristics and chemical characteristics. There is a risk of adulteration, especially when the fake medicine were mixed in authentic medicine, it is difficult to detection. The key to control the quality and ensures the clinical efficacy is the good or bad, true or false of the bile power medicine. The STR typing technology is a method that according to differential typing of PCR amplified lengths to compare and identify individual organisms. Based on the principle of STR typing, the easily, rapid DNA fingerprinting method to identify the bile power and adulteration was established.The original animal or bile powder of pigs, cattle, sheep, chickens, ducks, geese, snakes, bears, fish were collected, the 12 S-L1091/12 S-H1478 and 16 S-L3428/16 S-H3667 was obtained by sifted, the DNA fingerprinting of the bile power and adulteration was obtained by STR typing. Every species has different STR fingerprints, so different species can be identified. Besides, the fingerprints have both the authentic and fake's information, the adulteration of authentic and fake can be identified. Therefore, the method to identify the bile power and adulteration was achieved through the combination of two primers. The DNA fingerprinting method established in this study can also be used for other animal medicine.

GABA consumption during early pregnancy impairs endometrial receptivity and embryo development in mice.

γ-Aminobutyrate (GABA) is commonly used as a food supplement and a health care product by young females, due to its positive roles in relieving stress, alleviating anxiety, and improving sleep. However, its recommended daily dose in different products varies widely. Besides, it is unknown whether, and how, GABA consumption during early pregnancy influences pregnancy establishment. In this study, we found that when pregnant mice were treated with a high (12.5 mg/g) dose of GABA (orally) during preimplantation, there was a reduction in the number of implantation sites on day 5 of pregnancy. Also, among these unimplanted embryos, most exhibited morphological degeneration and developmental retardation, and only a few of them developed into blastocysts but could not implant into the uterus. Moreover, the expression of uterine receptivity-related factors-LIF, E-cadherin, and HOXA10-were all downregulated, while the number of uterine glands was reduced in the high GABA dose group. Finally, in vitro results demonstrated that GABA (ranging from 10 to 50 µg/µL) markedly inhibited preimplantation embryo development in a dose-response manner. However, this inhibitory effect was not observed when the embryos were pretreated with 40 µΜ 2-hydroxysaclofen, a GABAB antagonist, indicating that GABA exerts its inhibitory effects via its B-type receptor. Our results suggest that exposure to certain GABA concentrations, during early pregnancy, can impair preimplantation embryo development via its B-type receptor, and endometrial receptivity, which greatly disturbs early embryo implantation in mice. These findings could raise concerns about GABA consumption during the early stages of pregnancy.

KChIP3 N-Terminal 31-50 Fragment Mediates Its Association with TRPV1 and Alleviates Inflammatory Hyperalgesia in Rats.

Potassium voltage-gated channel interacting protein 3 (KChIP3), also termed downstream regulatory element antagonist modulator (DREAM) and calsenilin, is a multifunctional protein belonging to the neuronal calcium sensor (NCS) family. Recent studies revealed the expression of KChIP3 in dorsal root ganglion (DRG) neurons, suggesting the potential role of KChIP3 in peripheral sensory processing. Herein, we show that KChIP3 colocalizes with transient receptor potential ion channel V1 (TRPV1), a critical molecule involved in peripheral sensitization during inflammatory pain. Furthermore, the N-terminal 31-50 fragment of KChIP3 is capable of binding both the intracellular N and C termini of TRPV1, which substantially decreases the surface localization of TRPV1 and the subsequent Ca2+ influx through the channel. Importantly, intrathecal administration of the transmembrane peptide transactivator of transcription (TAT)-31-50 remarkably reduces Ca2+ influx via TRPV1 in DRG neurons and alleviates thermal hyperalgesia and gait alterations in a complete Freund's adjuvant-induced inflammatory pain model in male rats. Moreover, intraplantar injection of TAT-31-50 attenuated the capsaicin-evoked spontaneous pain behavior and thermal hyperalgesia, which further strengthened the regulatory role of TAT-31-50 on TRPV1 channel. In addition, TAT-31-50 could also alleviate inflammatory thermal hyperalgesia in kcnip3-/- rats generated in our study, suggesting that the analgesic effect mediated by TAT-31-50 is independent of endogenous KChIP3. Our study reveals a novel peripheral mechanism for the analgesic function of KChIP3 and provides a potential analgesic agent, TAT-31-50, for the treatment of inflammatory pain.SIGNIFICANCE STATEMENT Inflammatory pain arising from inflamed or injured tissues significantly compromises the quality of life in patients. This study aims to elucidate the role of peripheral potassium channel interacting protein 3 (KChIP3) in inflammatory pain. Direct interaction of the KChIP3 N-terminal 31-50 fragment with transient receptor potential ion channel V1 (TRPV1) was demonstrated. The KChIP3-TRPV1 interaction reduces the surface localization of TRPV1 and thus alleviates heat hyperalgesia and gait alterations induced by peripheral inflammation. Furthermore, the transmembrane transactivator of transcription (TAT)-31-50 peptide showed analgesic effects on inflammatory hyperalgesia independently of endogenous KChIP3. This work reveals a novel mechanism of peripheral KChIP3 in inflammatory hyperalgesia that is distinct from its classical role as a transcriptional repressor in pain modulation.

From General Aberrant Alternative Splicing in Cancers and Its Therapeutic Application to the Discovery of an Oncogenic DMTF1 Isoform.

Alternative pre-mRNA splicing is a crucial process that allows the generation of diversified RNA and protein products from a multi-exon gene. In tumor cells, this mechanism can facilitate cancer development and progression through both creating oncogenic isoforms and reducing the expression of normal or controllable protein species. We recently demonstrated that an alternative cyclin D-binding myb-like transcription factor 1 (DMTF1) pre-mRNA splicing isoform, DMTF1ß, is increasingly expressed in breast cancer and promotes mammary tumorigenesis in a transgenic mouse model. Aberrant pre-mRNA splicing is a typical event occurring for many cancer-related functional proteins. In this review, we introduce general aberrant pre-mRNA splicing in cancers and discuss its therapeutic application using our recent discovery of the oncogenic DMTF1 isoform as an example. We also summarize new insights in designing novel targeting strategies of cancer therapies based on the understanding of deregulated pre-mRNA splicing mechanisms.

Determination of dihydroartemisinic acid in Artemisia annua L. by gas chromatography with flame ionization detection.

Dihydroartemisinic acid (DHAA) is the direct precursor to artemisinin, an effective anti-malaria compound from Artemisia annua L. (A. annua), and it can be transformed to artemisinin without the catalysis of enzyme. A rapid and sensitive analysis of DHAA in A. annua is needed to screen excellent plant resources aimed to improve artemisinin production. In order to develop a rapid and sensitive determination method for DHAA in plant, the extraction and analysis conditions were extensively investigated in the present work. As a result, extraction of powdered A. annua leaves at 55°C for 50 min with chloroform resulted in the highest yield of DHAA, with a recovery of >98%. The precision of this gas chromatographic procedure ranged from 1.22 to 2.94% for intra-day and from 1.69 to 4.31% for inter-day, respectively. The accuracy was 99.55-103.02% for intra-day and 98.86-99.98% for inter-day, respectively. The measured LOQ and LOD values of the proposed method reached 5.00 and 2.00 µg/mL, respectively. Validation indicated the method was robust, quick, sensitive and adequate for DHAA analysis.

Study of CO2 cyclic absorption stability of CaO-based sorbents derived from lime mud purified by sucrose method.

Using lime mud (LM) purified by sucrose method, derived from paper-making industry, as calcium precursor, and using mineral rejects-bauxite-tailings (BTs) from aluminum production as dopant, the CaO-based sorbents for high-temperature CO2 capture were prepared. Effects of BTs content, precalcining time, and temperature on CO2 cyclic absorption stability were illustrated. The cyclic carbonation behavior was investigated in a thermogravimetric analyzer (TGA). Phase composition and morphologies were analyzed by XRD and SEM. The results reflected that the as-synthesized CaO-based sorbent doped with 10 wt% BTs showed a superior CO2 cyclic absorption-desorption conversion during multiple cycles, with conversion being >38 % after 50 cycles. Occurrence of Ca12Al14O33 phase during precalcination was probably responsible for the excellent CO2 cyclic stability.

Associations between serum-intact parathyroid hormone, serum 25-hydroxyvitamin D, oral vitamin D analogs and metabolic syndrome in peritoneal dialysis patients: a multi-center cross-sectional study.

INTRODUCTION: Although previous studies have suggested associations between serum intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25(OH)D) and metabolic syndrome (MS) in the general population, these associations are still uncharacterized in peritoneal dialysis (PD) patients. METHODS: In total, 837 prevalent PD patients from 5 centers in China were enrolled between April 1, 2011 and November 1, 2011. The demographic data, biochemical parameters and medical records were collected, except for serum 25(OH)D which was measured in 347 of 837 patients. The definition of MS was modified from National Cholesterol Education Program Third Adult Treatment Panel (NCEP-ATPIII). RESULTS: 55.4% of 837 patients were found to have MS. The median concentration of iPTH, 25(OH)D and doses of oral vitamin D analogs for participants with MS was significantly lower than those without MS. The iPTH, 25(OH)D values and doses of vitamin D analogs were all associated with one or more components of MS. After multivariate adjustment, low serum iPTH values and oral vitamin D analogs, rather than serum 25(OH)D, were significantly associated with the presence of MS, abnormal fasting blood glucose (FBG) and high-density lipoprotein cholesterol (HDL-C). Compared to iPTH < 130 pg/mL, iPTH 130-585 pg/mL and > 585 pg/mL were associated with a lower risk of MS with adjusted odds ratio (OR) of 0.59 and 0.33, respectively. Taking vitamin D analogs was also associated with a lower risk of MS with adjusted OR of 0.55. CONCLUSIONS: Serum iPTH and the use of active vitamin D supplements rather than serum 25(OH)D were independently associated with the presence of MS in patients on PD.

Huang-Lian-Jie-Du-Decotion induced protective autophagy against the injury of cerebral ischemia/reperfusion via MAPK-mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian-Jie-Du-Decotion (HLJDD, Hwangryun-Hae-Dok-Decotion in Japan), an ancient antipyretic and detoxifying traditional Chinese medicine formula, was reported to have protective effect on ischemic stroke. AIM OF THE RESEARCH: To investigate the therapeutic effect of HLJDD on ischemic stroke and explore its mode of action. MATERIAL AND METHODS: A model of ischemic stroke in the rat was established after transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Rats were assigned randomly to groups of control, sham, transient ischemia/reperfusion (I/R), and three treatment groups by HLJDD at 2.5, 5.0, 10.0mg/kg. The neurological deficit, the cerebral infarct size, morphology abnormality, biochemical parameters were examined, and the levels of relevant proteins were determined by immunoblotting analysis to evaluate the protective effects of HLJDD on ischemic stroke and explore the underlying mechanism. RESULTS: Compared with I/R group, HLJDD significantly ameliorated neurological deficit and histopathology changes, decreased infarct area, and restored the levels of biochemical indicators including nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), total superoxide dismutase (T-SOD), Cu/Zn-SOD, Mn-SOD and glutathione peroxidase (GSH-PX). HLJDD also notably elevated the levels of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1, and other autophagy related genes (Atgs), promoted the activation of extracellular signal-regulated kinases (ERK), protein kinase B (Akt), 3-phosphoinositide-dependent kinase (PDK1), and inhibited the activation of mammalian target of rapamycin (mTOR), c-Jun N-terminal protein kinases (JNK), p38, phosphatase and tensin homolog (PTEN). CONCLUSION: HLJDD showed neuroprotective effects on ischemic stroke, at least in part to the induced protective autophagy via the regulation of mitogen-activated protein kinase (MAPK) signals. This Akt-independent protective autophagy is favorable in the treatment of stroke, avoiding unfavorable side-effects associated with the inactivation of Akt. The efficacy of HLJDD on ischemic stroke and its safety warranted by its long-term clinical use in traditional Chinese medicine favored further study to develop HLJDD as an effective therapeutic agent to treat ischemic stroke.