Reactivation of the G1 enhancer landscape underlies core circuitry addiction to SWI/SNF.

Several cancer core regulatory circuitries (CRCs) depend on the sustained generation of DNA accessibility by SWI/SNF chromatin remodelers. However, the window when SWI/SNF is acutely essential in these settings has not been identified. Here we used neuroblastoma (NB) cells to model and dissect the relationship between cell-cycle progression and SWI/SNF ATPase activity. We find that SWI/SNF inactivation impairs coordinated occupancy of non-pioneer CRC members at enhancers within 1 hour, rapidly breaking their autoregulation. By precisely timing inhibitor treatment following synchronization, we show that SWI/SNF is dispensable for survival in S and G2/M, but becomes acutely essential only during G1 phase. We furthermore developed a new approach to analyze the oscillating patterns of genome-wide DNA accessibility across the cell cycle, which revealed that SWI/SNF-dependent CRC binding sites are enriched at enhancers with peak accessibility during G1 phase, where they activate genes involved in cell-cycle progression. SWI/SNF inhibition strongly impairs G1-S transition and potentiates the ability of retinoids used clinically to induce cell-cycle exit. Similar cell-cycle effects in diverse SWI/SNF-addicted settings highlight G1-S transition as a common cause of SWI/SNF dependency. Our results illustrate that deeper knowledge of the temporal patterns of enhancer-related dependencies may aid the rational targeting of addicted cancers.

Cancer cells driven by runaway transcription factor networks frequently depend on the cellular machinery that promotes DNA accessibility. For this reason, recently developed small molecules that impair SWI/SNF (or BAF) chromatin remodeling activity have been under active evaluation as anti-cancer agents. However, exactly when SWI/SNF activity is essential in dependent cancers has remained unknown. By combining live-cell imaging and genome-wide profiling in neuroblastoma cells, Cermakova et al. discover that SWI/SNF activity is needed for survival only during G1 phase of the cell cycle. The authors reveal that in several cancer settings, dependency on SWI/SNF arises from the need to reactivate factors involved in G1-S transition. Because of this role, authors find that SWI/SNF inhibition potentiates cell-cycle exit by retinoic acid.

A distinct dimer configuration of a diatom Get3 forming a tetrameric complex with its tail-anchored membrane cargo.

BACKGROUND: Most tail-anchored (TA) membrane proteins are delivered to the endoplasmic reticulum through a conserved posttranslational pathway. Although core mechanisms underlying the targeting and insertion of TA proteins are well established in eukaryotes, their role in mediating TA protein biogenesis in plants remains unclear. We reported the crystal structures of algal arsenite transporter 1 (ArsA1), which possesses an approximately 80-kDa monomeric architecture and carries chloroplast-localized TA proteins. However, the mechanistic basis of ArsA2, a Get3 (guided entry of TA proteins 3) homolog in plants, for TA recognition remains unknown. RESULTS: Here, for the first time, we present the crystal structures of the diatom Pt-Get3a that forms a distinct ellipsoid-shaped tetramer in the open (nucleotide-bound) state through crystal packing. Pulldown assay results revealed that only tetrameric Pt-Get3a can bind to TA proteins. The lack of the conserved zinc-coordination CXXC motif in Pt-Get3a potentially leads to the spontaneous formation of a distinct parallelogram-shaped dimeric conformation in solution, suggesting a new dimer state for subsequent tetramerization upon TA targeting. Pt-Get3a nonspecifically binds to different subsets of TA substrates due to the lower hydrophobicity of its α-helical subdomain, which is implicated in TA recognition. CONCLUSIONS: Our study provides new insights into the mechanisms underlying TA protein shielding by tetrameric Get3 during targeting to the diatom's cell membrane.

The use of bubble charts in analyzing second stage cesarean delivery rates.

BACKGROUND: The incidence of second stage cesarean delivery has been rising globally because of the failure or the anticipated difficulty of performing instrumental delivery. Yet, the best way to interpret the figure and its optimal rate remain to be determined. This is because it is strongly influenced by the practice of other 2 modes of birth, namely cesarean delivery performed before reaching the second stage and assisted vaginal birth during the second stage. In this regard, a bubble chart that can display 3-dimensional data through its x-axis, y-axis, and the size of each plot (presented as a bubble) may be a suitable method to evaluate the relationship between the rates of these 3 modes of births. OBJECTIVE: This study aimed to conduct an epidemiologic study on the incidence of second stage cesarean deliveries rates among >300,000 singleton term births in 10 years from 8 obstetrical units and to compare their second stage cesarean delivery rates in relation to their pre-second stage cesarean delivery rates and assisted vaginal birth rates using a bubble chart. STUDY DESIGN: The territory-wide birth data collected between 2009 and 2018 from all 8 public obstetrical units (labelled as A to H) were reviewed. The inclusion criteria were all singleton pregnancies with cephalic presentation that were delivered at term (≥37 weeks' gestation). Pre-second stage cesarean delivery rate was defined as all elective cesarean deliveries and those emergency cesarean deliveries that occurred before full cervical dilatation was achieved as a proportion of the total number of births. The second stage cesarean delivery rate and assisted vaginal birth rate were calculated according to the respective mode of delivery as a proportion of the number of cases that reached full cervical dilatation. The rates of these 3 modes of births were compared among the parity groups and among the 8 units. Using a bubble chart, each unit's second stage cesarean delivery rate (y-axis) was plotted against its pre-second stage cesarean delivery rate (x-axis) as a bubble. Each unit's second stage cesarean delivery to assisted vaginal birth ratio was represented by the size of the bubble. RESULTS: During the study period, a total of 353,434 singleton cephalic presenting term pregnancies were delivered in the 8 units, and 180,496 (51.1%) were from nulliparous mothers. When compared with the multiparous group, the nulliparous group had a significantly lower pre-second stage cesarean delivery rate (18.58% vs 21.26%; P<.001) but a higher second stage cesarean delivery rate (0.79% vs 0.22%; P<.001) and a higher assisted vaginal birth rate (17.61% vs 3.58%; P<.001). Using the bubble of their averages as a reference point in the bubble chart, the 8 units' bubbles were clustered into 5 regions indicating their differences in practice: unit B and unit H were close to the average in the center. Unit A and unit F were at the upper right corner with a higher pre-second stage cesarean delivery rate and second stage cesarean delivery rate. Unit D and unit E were at the opposite end. Unit C was at the upper left corner with a low pre-second stage cesarean delivery rate but a high second stage cesarean delivery rate, whereas unit G was at the opposite end. Unit C and unit G were also in the extremes in terms of pre-second stage cesarean delivery to assisted vaginal birth ratio (0.09 and 0.01, respectively). Although some units seemed to have very similar second stage cesarean delivery rates, their obstetrical practices were differentiated by the bubble chart. CONCLUSION: The second stage cesarean delivery rate must be evaluated in the context of the rates of pre-second stage cesarean delivery and assisted vaginal birth. A bubble chart is a useful method for analyzing the relationship among these 3 variables to differentiate the obstetrical practice between different units.

Decoding the essence of two-character Chinese words: Unveiling valence, arousal, concreteness, familiarity, and imageability through word norming.

Investigation of affective and semantic dimensions of words is essential for studying word processing. In this study, we expanded Tse et al.'s (Behav Res Methods 49:1503-1519, 2017; Behav Res Methods 55:4382-4402, 2023) Chinese Lexicon Project by norming five word dimensions (valence, arousal, familiarity, concreteness, and imageability) for over 25,000 two-character Chinese words presented in traditional script. Through regression models that controlled for other variables, we examined the relationships among these dimensions. We included ambiguity, quantified by the standard deviation of the ratings of a given lexical variable across different raters, as separate variables (e.g., valence ambiguity) to explore their connections with other variables. The intensity-ambiguity relationships (i.e., between normed variables and their ambiguities, like valence with valence ambiguity) were also examined. In these analyses with a large pool of words and controlling for other lexical variables, we replicated the asymmetric U-shaped valence-arousal relationship, which was moderated by valence and arousal ambiguities. We also observed a curvilinear relationship between valence and familiarity and between valence and concreteness. Replicating Brainerd et al.'s (J Exp Psychol Gen 150:1476-1499, 2021; J Mem Lang 121:104286, 2021) quadratic intensity-ambiguity relationships, we found that the ambiguity of valence, arousal, concreteness, and imageability decreases as the value of these variables is extremely low or extremely high, although this was not generalized to familiarity. While concreteness and imageability were strongly correlated, they displayed different relationships with arousal, valence, familiarity, and valence ambiguity, suggesting their distinct conceptual nature. These findings further our understanding of the affective and semantic dimensions of two-character Chinese words. The normed values of all these variables can be accessed via https://osf.io/hwkv7 .

Taboo language across the globe: A multi-lab study.

The use of taboo words represents one of the most common and arguably universal linguistic behaviors, fulfilling a wide range of psychological and social functions. However, in the scientific literature, taboo language is poorly characterized, and how it is realized in different languages and populations remains largely unexplored. Here we provide a database of taboo words, collected from different linguistic communities (Study 1, N = 1046), along with their speaker-centered semantic characterization (Study 2, N = 455 for each of six rating dimensions), covering 13 languages and 17 countries from all five permanently inhabited continents. Our results show that, in all languages, taboo words are mainly characterized by extremely low valence and high arousal, and very low written frequency. However, a significant amount of cross-country variability in words' tabooness and offensiveness proves the importance of community-specific sociocultural knowledge in the study of taboo language.

Clear Cell Sarcoma of the Kidney (CCSK) With BCOR-CCNB3 Fusion: A Rare Case Report With a Brief Review of the Literature.

Pediatric renal tumors are a rare entity and majority of these tumors are accounted for by Wilms tumor. The second most common renal tumor is clear cell sarcoma of the kidney (CSSK). Most of the CSSK have either BCOR-internal tandem duplication (ITD) or YWHAE-NUTM2B/E fusion. The sarcomas with BCOR-CCNB3 fusion are well documented in soft tissue and bone tumors, but are extremely rare in the pediatric renal setting. We are reporting an extremely rare case of pediatric clear cell sarcoma of the kidney (CSSK) with BCOR-CCNB3 fusion, which was a diagnostic challenge on morphological grounds. A final diagnosis could only be reached after multiple reviews and NGS based RNA fusion testing. We have also performed a brief review of literature which revealed eight (8) other cases of this rare entity.

The Chinese Lexicon Project II: A megastudy of speeded naming performance for 25,000+ traditional Chinese two-character words.

Using a megastudy approach, (Tse et al., 2017 Behavior Research Methods, 49, 1503-1519) established a large-scale repository of lexical variables and lexical decision responses for more than 25,000 traditional Chinese two-character words. In the current study, we expand their database by collecting norms for speeded naming reaction times (RTs) and accuracy rates, and compiling more lexical variables (e.g., phonological consistency and semantic neighborhood size). Following Tse et al.'s procedure, about 33 college-aged native Cantonese speakers in Hong Kong read aloud each word. We conducted item-level regression analyses to test the relative predictive power of orthographic variables (e.g., stroke count), phonological variables (e.g., phonological consistency), and semantic variables (e.g., semantic transparency) in naming performance. We also compared the effects of lexical variables on naming performance and Tse et al.'s lexical decision performance to examine the extent to which effects are task-specific or task-general. Freely accessible to the research community, this resource provides a valuable addition to other influential mega-databases, such as the English Lexicon Project (Balota et al., 2004 Journal of Experimental Psychology: General, 133, 283-316), and furthers our understanding of Chinese word recognition processes.

A Quality Improvement Initiative to Reduce Abdominal X-ray use in Pediatric Patients Presenting with Constipation.

OBJECTIVE: To decrease the percentage of patients undergoing an abdominal radiograph for evaluation of constipation within 24 hours of their initial gastroenterology visit. STUDY DESIGN: In January 2015, we implemented a quality improvement, evidence-based guideline (EBG) aimed at standardizing the initial assessment of patients presenting for a new outpatient gastroenterology visit with a primary complaint of constipation. Over the subsequent 5 years, we followed the clinical impact of this guideline initiation with the goal of decreasing unnecessary abdominal radiograph use by 10% within 1 year of EBG launch. Patients older than 6 months and younger than 19 years were included. RESULTS: In total, 6723 patients completed new patient gastroenterology visits for a primary diagnosis of constipation between 2013 and 2019. Of these, 993 (14.8%) patients had abdominal radiographs taken within 24 hours of their initial visit. Over the 7 years of this project, a mean frequency of abdominal radiograph use decreased from 24% to less than 11%. In addition, a 57% decrease in hospital charges related to decreased radiograph use for constipation was found. No increases in subsequent emergency department visits or hospitalization for constipation within 30 days of patients' initial visits were seen. CONCLUSIONS: Through local adoption of an EBG, routine use of abdominal radiographs taken during a patient's initial outpatient gastroenterology visit for constipation decreased by more than 50%. This reduction was maintained over a subsequent 5-year period without any detrimental side effects.

Ruthenafuran Complexes Supported by the Bipyridine-Bis(diphenylphosphino)methane Ligand Set: Synthesis and Cytotoxicity Studies.

Mononuclear and dinuclear Ru(II) complexes cis-[Ru(κ2-dppm)(bpy)Cl2] (1), cis-[Ru(κ2-dppe)(bpy)Cl2] (2) and [Ru2(bpy)2(µ-dpam)2(µ-Cl)2](Cl)2 ([3](Cl)2) were prepared from the reactions between cis(Cl), cis(S)-[Ru(bpy)(dmso-S)2Cl2] and diphosphine/diarsine ligands (bpy = 2,2'-bipyridine; dppm = 1,1-bis(diphenylphosphino)methane; dppe = 1,2-bis(diphenylphosphino)ethane; dpam = 1,1-bis(diphenylarsino)methane). While methoxy-substituted ruthenafuran [Ru(bpy)(κ2-dppe)(C^O)]+ ([7]+; C^O = anionic bidentate [C(OMe)CHC(Ph)O]- chelate) was obtained as the only product in the reaction between 2 and phenyl ynone HC≡C(C=O)Ph in MeOH, replacing 2 with 1 led to the formation of both methoxy-substituted ruthenafuran [Ru(bpy)(κ2-dppm)(C^O)]+ ([4]+) and phosphonium-ring-fused bicyclic ruthenafuran [Ru(bpy)(P^C^O)Cl]+ ([5]+; P^C^O = neutral tridentate [(Ph)2PCH2P(Ph)2CCHC(Ph)O] chelate). All of these aforementioned metallafuran complexes were derived from Ru(II)-vinylidene intermediates. The potential applications of these metallafuran complexes as anticancer agents were evaluated by in vitro cytotoxicity studies against cervical carcinoma (HeLa) cancer cell line. All the ruthenafuran complexes were found to be one order of magnitude more cytotoxic than cisplatin, which is one of the metal-based anticancer agents being widely used currently.

RPA resolves conflicting activities of accessory proteins during reconstitution of Dmc1-mediated meiotic recombination.

Dmc1 catalyzes homology search and strand exchange during meiotic recombination in budding yeast and many other organisms including humans. Here we reconstitute Dmc1 recombination in vitro using six purified proteins from budding yeast including Dmc1 and its accessory proteins RPA, Rad51, Rdh54/Tid1, Mei5-Sae3 and Hop2-Mnd1 to promote D-loop formation between ssDNA and dsDNA substrates. Each accessory protein contributed to Dmc1's activity, with the combination of all six proteins yielding optimal activity. The ssDNA binding protein RPA plays multiple roles in stimulating Dmc1's activity including by overcoming inhibitory effects of ssDNA secondary structure on D-loop reactions, and by elongating D-loops. In addition, we demonstrate that RPA limits inhibitory interactions of Hop2-Mnd1 and Rdh54/Tid1 that otherwise occur during assembly of Dmc1-ssDNA nucleoprotein filaments. Finally, we report interactions between the proteins employed in the biochemical reconstitution including a direct interaction between Rad51 and Dmc1 that is enhanced by Mei5-Sae3.

The influence of congruency proportion, target eccentricity, and valence strength on the spatial-valence metaphoric congruency effect in a word valence judgment task.

In a word valence judgment task, positive words (e.g., excellence) are judged faster when presented at the top (congruent position) than at the bottom of the screen (incongruent position), whereas the opposite pattern occurs for negative words (e.g., disaster). This spatial-valence metaphoric congruency effect reflects top-positive/bottom-negative metaphoric association and may be attributed to at least three possible mechanisms: spreading activation between spatial and valence concepts (activation account), epistemic function that a conceptual metaphor serves to reduce the uncertainty associated with valence concepts (epistemic account), and/or the extent to which spatial-valence metaphoric association is relevant to task demand (relevance account). In three experiments, we manipulated congruency proportion, target eccentricity, and valence strength in a word valence judgment task to test these three possible accounts. Results showed that the metaphoric congruency effect was larger when a high (vs. equal) proportion of targets appears in congruent, relative to incongruent, position, and for targets with strong (vs. weak) valence. However, the effect in reaction time measure was not modulated by whether the target appeared in the position being near vs. far away from the center of the screen. The overall findings are better accommodated by the relevance account. The implications of the current findings on other theoretical accounts, such as Conceptual Metaphor Theory and polarity correspondence account, are also discussed.

Construal-level priming does not modulate memory performance in Deese-Roediger/McDermott paradigm.

Construal level refers to the level of abstractness that events and objects are represented, with high construal level promoting relational processing, whereas low construal level, item-specific processing. Three experiments (total N = 432) were conducted to investigate how priming construal level affects encoding of Deese/Roediger-McDermott (DRM) lists (e.g., bed, dream … converged to a critical item sleep), and then modulates free recall and recognition memory performance. Before and during list encoding, participants were primed with high/low construal level by identifying global/local letter in composite letters in a Navon task, choosing category (e.g., body)/exemplar (e.g., liver) to common objects (e.g., internal organ) in a two-alternative-forced-choice task, or by narrating on a particular incident they had power over other people or someone else had power over them. Half of critical items (and yoked associates) were studied and half were not, so their hit rates, false alarm rates, and memory sensitivity were measured. Results showed the typical false memory effect and lower memory sensitivity for critical items (vs. yoked associates), but there was no significant effect of primed construal level on memory performance in all experiments, despite our sample sizes ensuring strong statistical power. Hence, construal-level priming does not modulate memory performance in the DRM task.

Normative data for Chinese-English paired associates.

Paired-associate learning is one of the most commonly used paradigms to study human memory. In many of these studies, participants are typically told to learn foreign language-English translations, such as Swahili-English or Lithuanian-English pairs. One limitation of these currently available foreign language-English translation norms is that their foreign languages are based on the alphabetic writing system, thereby preventing researchers from generalizing their findings to languages based on logographic writing systems. In the present study we collected normative data for 160 Chinese-English word pairs. Participants completed three study-test cycles, followed by metacognitive judgments on their learning experience. For each pair, we report recall performance, recall latency, ease of learning, and judgments of learning. A simultaneous multiple regression analysis with frequency (of both the English word and the Chinese character), word length (English), and number of strokes (Chinese) as predictors revealed that a greater number of strokes (or higher visual complexity) for the Chinese characters predicted lower target recall.

NK cells produce high levels of IL-10 early after allogeneic stem cell transplantation and suppress development of acute GVHD.

Natural killer (NK) cells rapidly reconstitute following allogeneic stem cell transplantation (allo-SCT), at the time when alloreactive T cell immunity is being established. We investigated very early NK cell reconstitution in 82 patients following T cell-depleted allo-SCT. NK cell number rapidly increased, exceeding T cell reconstitution such that the NK:T cell ratio was over 40 by day 14. NK cells at day 14 (NK-14) were donor-derived, intensely proliferating and expressed chemokine receptors targeted to lymphoid and peripheral tissue. Spontaneous production of the immunoregulatory cytokine IL-10 was observed in over 70% of cells and transcription of cytokines and growth factors was augmented. NK-14 cell number was inversely correlated with the incidence of grade II-IV acute graft versus host disease (GVHD). These findings reveal that robust reconstitution of immunoregulatory NK cells by day 14 after allo-SCT is an important determinant of the clinical outcome, suggesting that NK cells may suppress the development of the T cell-mediated alloreactive immune response through production of IL-10.

A TCM formula comprising Sophorae Flos and Lonicerae Japonicae Flos alters compositions of immune cells and molecules of the STAT3 pathway in melanoma microenvironment.

A traditional Chinese medicine (TCM) formula (SL) comprising Sophorae Flos and Lonicerae Japonicae Flos was used for treating melanoma in ancient China. We have previously shown that an ethanolic extract of SL (SLE) possesses anti-melanoma effects and suppresses STAT3 signaling in vitro and in vivo. STAT3 has been linked to the development of melanoma immunosuppressive microenvironment. In this work, we investigated whether SLE inhibits melanoma growth by reprogramming the tumor microenvironment in mouse and co-culture cell models. In B16F10 melanoma-bearing mice, we found that intragastric administration of SLE (1.2 g/kg) dramatically inhibited tumor growth. This observation was associated with the downregulation of protein levels of phospho-STAT3 (Tyr 705) and STAT3-regulated immunosuppressive cytokines, and mRNA levels of STAT3-targeted genes involved in tumor growth and immune evasion. We also observed increased Th, Tc and dendritic cells in the melanomas and spleens in SLE-treated mice compared to that in control mice. In a co-culture system composed of B16F10 cells and mouse primary splenic lymphocytes, it was found that SLE not only inhibited STAT3 activation in B16F10 cells, but also downregulated mRNA levels of STAT3-targeted genes in the splenic lymphocytes. In this co-culture setting, SLE decreased the levels of STAT3-regulated immunosuppressive cytokines, increased the percentages of Th, Tc and dendritic cells as well. Furthermore, effects of SLE on STAT3 phosphorylation, cytokine levels and immune cell subtype percentages were significantly weaker in the B16STAT3C cells (stable cells harboring a constitutively active STAT3 variant STAT3C)/splenic lymphocytes co-culture system than in the B16V cells (cells stably transfected with the empty vector)/splenic lymphocytes co-culture system, indicating that STAT3 over-activation diminishes SLE's effects. In summary, our findings indicate that reprograming the immune microenvironment, partially mediated by inhibiting STAT3 signaling, contributes to the anti-melanoma mechanisms of SLE. This study provides further pharmacological groundwork for developing SLE as a modern agent for melanoma prevention/treatment, and supports the notion that reprograming immunosuppressive microenvironment is a viable anti-melanoma strategy.

Placental histopathology in preterm fetal growth restriction.

AIMS: Approximately 6-9% pregnancies are affected by fetal growth restriction (FGR). Placental alterations related to utero-placental insufficiency in FGR may induce placental vascular remodelling to the detriment of the fetus. The objective of this article was to study histopathological features of placentae in a cohort of preterm growth-restricted infants in comparison to a cohort of preterm appropriately grown infants. METHODS: In a cohort of 40 preterm infants of 28-32 weeks' gestation, placental histopathology was evaluated by a histopathologist, who was blinded to the identity of the grouping. Twenty infants had FGR, while 20 were appropriate for gestational age (AGA). Predefined histopathological characteristics were assessed based on the Amsterdam Placental Workshop Group Consensus Statement. RESULTS: The gestational age and birthweight of the FGR and AGA cohorts were 29.8 ± 1.3 versus 30 ± 0.9 weeks, P = 0.78 and 923 ± 168 versus 1403 ± 237 g, <0.001, respectively. Maternal vascular malperfusion, accelerated villous maturation and fetal vascular malperfusion were features that were significantly more common in FGR placentae. CONCLUSION: Based on the results of the present study, specific placental histopathological changes may be present in FGR placentae, which may reflect the effects of utero-placental insufficiency.

Species Identification of Fragmented or Faded Shed Snake Skins by Light Microscopy.

Few convenient/expeditious methods for identifying the species of shed snake skins in specific areas have been developed. The scales on shed snake skins are permeable to light and can be examined by light microscopy (LM), which is of higher availability-especially for wild animal researchers and citizen scientists-than conventional approach which examines the scale microstructures by scanning electron microscopy. We collected and examined a total of 801 shed samples or scale specimens from 53 snake species in Taiwan and adjacent islands, and developed the first guide to identify the fragmented or faded shed skins of most snake species by LM. Morphological characters of scales can be examined by LM include the apical notch, apical pits, apical lobes, keels, scale symmetry, unpigmented spots (mechanoreceptor-like organs), interscale follicles, cross/longitudinal micro-ridge, oberhautchen cells, rows of spines, light/tiny dots, and other microstructures. The microstructures on the scale specimens prepared by the stripped method and the impression method were similar to those on shed skins when examined by LM. We investigated the variations of scale morphology associated with ontogeny, body region, and position on scales, discussed the character evolution of snake scale morphology, and certified that the interscale follicles and the unpigmented spots could also be useful characters for shed skin identification. The methods and results of this study could be applied to identify squamate skins/sloughs and even fecal remnants.

Comparison of the chemical profiles and inflammatory mediator-inhibitory effects of three Siegesbeckia herbs used as Herba Siegesbeckiae (Xixiancao).

BACKGROUND: Herba Siegesbeckiae (HS, Xixiancao in Chinese) is a commonly used traditional Chinese medicinal herb for soothing joints. In ancient materia medica books, HS is recorded to be the aerial part of Siegesbeckia pubescens Makino (SP) which is also the only origin of HS in the 1963 edition of the Chinese Pharmacopeia (ChP). The aerial parts of Siegesbeckia orientalis L. (SO) and Siegesbeckia glabrescens Makino (SG) have been included as two additional origins for HS in each edition of ChP since 1977. However, chemical and pharmacological comparisons among these three species have not been conducted. METHODS: An HPLC with diode array detector (HPLC-DAD) method combined with similarity analysis, hierarchical cluster analysis (HCA) and principal component analysis (PCA) was developed for comparing the fingerprint chromatograms of the three species. The inhibitory effects of the three species on NO production and IL-6 secretion in LPS-stimulated RAW264.7 macrophages were compared. RESULTS: Fingerprint chromatograms of the three species showed different profiles, but had 13 common peaks. Results from HCA and PCA of the common peaks demonstrated that all 14 herbal samples of the three species tended to be grouped and separated species dependently. The extents of inhibition on NO production and IL-6 secretion of the three species were different, with SG being the most and SP the least potent. CONCLUSIONS: Both chemical profiles and inflammatory mediator-inhibitory effects of the three species were different. These findings provide a chemical and pharmacological basis for determining whether the three species can all serve as the origins of HS.