Rosellichalasins A-H, cytotoxic cytochalasans from the endophytic fungus Rosellinia sp. Glinf021.

Eight new cytochalasans rosellichalasins A-H (1-8), as well as two new shunt metabolites rosellinins A (9) and B (10) before intramolecular Diels-Alder cycloaddition reaction in cytochalasan biosynthesis, along with nine known cytochalsans (11-19) were isolated from the endophytic fungus Rosellinia sp. Glinf021, which was derived from the medicinal plant Glycyrrhiza inflata. Their structures were characterized by extensive analysis of 1D and 2D NMR as well as HRESIMS spectra and quantum chemical ECD calculations. The cytotoxic activities of these compounds were evaluated against four human cancer cell lines including HCT116, MDA-MB-231, BGC823, and PANC-1 with IC50 values ranging from 0.5 to 58.2 µM.

Yi-Qi-Huo-Xue decoction alleviates intracerebral hemorrhage injury through inhibiting neuronal autophagy of ipsilateral cortex via BDNF/TrkB pathway.

BACKGROUND: Yi-Qi-Huo-Xue Decoction (YQHXD), a traditional Chinese medicine formula, has demonstrated efficacy in the clinical treatment of intracerebral hemorrhage (ICH) for over a decade. Nevertheless, the precise pharmacotherapeutic compounds of YQHXD capable of penetrating into cerebral tissue and the pharmacological underpinnings of YQHXD remain ambiguous. METHODS: The active components of YQHXD in rat brains was analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The potential targets, pathways and biological progresses of YQHXD ameliorating ICH induced injury was predicted by network pharmacology. Moreover, collagenase-induced ICH rat model, primary cortex neurons exposed to hemin and molecular docking were applied to validate the molecular mechanisms of YQHXD. RESULTS: Eleven active components of YQHXD were identified within the brains. Employing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, our investigation concentrated on the roles of autophagy and the BDNF/TrkB signaling pathway in the pharmacological context. The pharmacological results revealed that YQHXD alleviated neurological dysfunction, brain water content, brain swelling, and pathological injury caused by ICH. Meanwhile, YQHXD inhibited autophagy influx and autophagosome in vivo, and regulated cortex neuronal autophagy and TrkB/BDNF pathway both in vivo and in vitro. Subsequently, N-acetyl serotonin (NAS), a selective TrkB agonist, was employed to corroborate the significance of the BDNF/TrkB pathway in this process. The combination of NAS and YQHXD did not further enhance the protective efficacy of YQHXD in ICH rats. Additionally, outcomes of molecular docking analysis revealed that nine compounds of YQHXD exhibited potential regulatory effects on TrkB. CONCLUSIONS: Ipsilateral neuronal autophagy and BDNF/TrkB pathway were activated 72 h after ICH. YQHXD effectively resisted injury induced by ICH, which was related with suppression of ipsilateral neuronal autophagy via BDNF/TrkB pathway. This study provides novel insights into the therapeutic mechanisms of traditional Chinese medicine in the context of ICH treatment.

Superconductivity of cubic MB6 (M = Na, K, Rb, Cs).

Previous studies have shown that NaB6, KB6, and RbB6 adopting Pm3̄m are superconductors with a relatively high Tc under ambient conditions. In this paper, we conducted systematic structural and related properties research on CsB6 through a genetic evolution algorithm and total energy calculations based on density functional theory between 0 and 20 GPa. Our results reveal a cubic Pm3̄m CsB6, which is dynamically stable under the pressures we studied. We systematically calculated the formation enthalpies, electronic properties, and superconducting properties of Pm3̄m MB6 (M = Na, K, Rb, Cs). They all exhibit metallic features, and boron has high contributions to band structures, density of states, and electron-phonon coupling (EPC). The calculated results about the Helmholtz free energy difference of Pm3̄m CsB6 at 0, 10, and 20 GPa indicate that it is stable upon chemical decomposition (decomposition to simple substances Cs and B) from 0 to 400 K. The phonon density of states indicates that boron atoms occupy the high frequency area. The EPC results show that Pm3̄m CsB6 is a superconductor with Tc = 11.7 K at 0 GPa, close to NaB6 (13.1 K), KB6 (11.7 K), and RbB6 (11.3 K) at 0 GPa in our work, which indicates that boron atoms play an essential role in superconductivity: vibrations of B6 regular octagons lead to the high Tc of Pm3̄m MB6. Our work about Pm3̄m hexaborides provides a supplementary study on the borides of the group IA elements (without Fr and Li) and has an important guiding significance for the experimental synthesis of CsB6.

Rosellosides A and B, two phenyloxazole glycosides from Glycyrrhiza inflata-derived fungus Rosellinia sp. Glinf021.

Two new chlorinated phenyloxazole glycosides, named rosellosides A (1) and B (2), were isolated from the endophytic fungus Rosellinia sp. Glinf021, which was derived from the medicinal plant Glycyrrhiza inflata (Leguminosae). Both compounds were rare chlorinated polyketide glycosides bearing an oxazole moiety. Their structures were elucidated by analysis of the NMR and HRESIMS data, and their absolute configurations were determined by quantum chemical ECD calculations and X-ray crystallography.

Effects of Baduanjin exercise on patients with chronic nonspecific low back pain and surface electromyography signs of erector spinal muscle: A randomized controlled trial.

BACKGROUND: Chronic nonspecific low back pain (CNLBP) is a common disease usually with lower back muscle fatigue and injuries that may contribute to lumbar muscle imbalance and pain recurrence. This study aimed to examine the effectiveness of Baduanjin exercise on patients of CNLBP and to assess its impact on the surface electromyographic signals of the lumbar erector spinae muscle. METHODS: A total of 60 patients diagnosed with CNLBP were admitted from the Hubei Provincial Hospital of Traditional Chinese Medicine from March 2022 to December 2022. Those patients were randomly allocated into the Baduanjin group (n = 30) or the walking group (n = 30). Both groups received a 4-week intervention, with 5 training sessions per week. The numeric pain rating scale (the minimal clinically important difference = 2.4) and Oswestry Disability Index (the minimal clinically important difference = 13.4), electromyogram signals during lumbar flexion (FLEXAEMG), lumbar extension (EXTAEMG), and maximum lumbar flexion (MAEMG), the ratios of FLEXAEMG to MAEMG and EXTAEMG to MAEMG were collected at Baseline and posttreatment and compared using the Wilcoxon signed-rank test or Mann-Whitney U test. RESULTS: After treatment, the numeric pain rating scale score in the Baduanjin group exhibited a significant decrease compared to baseline (P < .05) and was found to be lower than that of the Walking group (mean difference 2.36; CI 95% -2.323 to -1.742; P = .001). Similarly, the Oswestry disability index in the Baduanjin group demonstrated a reduction compared to baseline (P < .05) and was lower than that of the Walking group (the mean difference 7.59; CI 95% -8.861 to -6.312; P = .001). The FLEXAEMG and EXTAEMG of both groups had a significant increase (P < .05), with the Baduanjin group demonstrating higher levels compared to the Walking group (P < .05). Conversely, the MAEMG of both groups displayed a significant decrease (P < .05), with the Baduanjin group exhibiting lower levels than the Walking group (P < .05). The FLEXAEMG to MAEMG and EXTAEMG to MAEMG in the Baduanjin group increased (P < .05) and were significantly higher than the Walking group (P < .05). CONCLUSION: Baduanjin exercise has shown to be highly effective in reducing low back pain and in promoting lumber dysfunction, due to its ability to improve the strength and flexibility of the lumbar erector spinae muscle.

Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy.

Cyclometalated iridium(III) complexes are of significant importance in the field of antitumor photodynamic therapy (PDT), whether they exist as single molecules or are incorporated into nanomaterials. Nevertheless, a comprehensive examination of the relationship between their molecular structure and PDT effectiveness remains awaited. The influencing factors of two-photon excited PDT can be anticipated to be further multiplied, particularly in relation to intricate nonlinear optical properties. At present, a comprehensive body of research on this topic is lacking, and few discernible patterns have been identified. In this study, through systematic structure regulation, the nitro-substituted styryl group and 1-phenylisoquinoline ligand containing YQ2 was found to be the most potent infrared two-photon excitable photosensitizer in a 4 × 3 combination library of cyclometalated Ir(III) complexes. YQ2 could enter cells via an energy-dependent and caveolae-mediated pathway, bind specifically to mitochondria, produce 1O2 in response to 808 nm LPL irradiation, activate caspases, and induce apoptosis. In vitro, YQ2 displayed a remarkable phototherapy index for both malignant melanoma (>885) and non-small-cell lung cancer (>1234) based on these functions and was minimally deleterious to human normal liver and kidney cells. In in vivo antitumor phototherapy, YQ2 inhibited tumor growth by an impressive 85% and could be eliminated from the bodies of mice with a half-life as short as 43 h. This study has the potential to contribute significantly to the development of phototherapeutic drugs that are extremely effective in treating large, profoundly located solid tumors as well as the understanding of the structure-activity relationship of Ir(III)-based PSs in PDT.

Endophytic fungus Colletotrichum sp. AP12 promotes growth physiology and andrographolide biosynthesis in Andrographis paniculata (Burm. f.) Nees.

Endophytic fungi can promote host plant growth, enhance antioxidant defense enzyme activity, and induce the biosynthesis and accumulation of secondarymetabolites. Therefore, using endophytic fungi to improve the quality and yield of medicinal plants or important crops is an effective means of regulation. Colletotrichum sp. AP12 has been reported to produce andrographolide compounds (ADCs). This study aimed to investigate the effects of AP12 and its elicitors on the growth, defense enzyme activity, accumulation, and transcription levels of key genes in Andrographis paniculata (Burm. f.) Nees (A. paniculata). Using fermentation method to prepare AP12 into the inactivated fermentation solution (IFS), fermentation solution (FS), inactivated mycelium solution (IMS), and mycelium solution (MS), and the results showed that all four fungal elicitor components (ECs) could promote A. paniculata growth, enhance antioxidant defense enzymes, and increase ADC content and yield, especially the IMS group that had the highest leaf area, whole plant dry weight, superoxide dismutase (SOD), catalase (CAT) enzyme activities, total lactone contents, and yields, which were 2.37-, 1.60-, 2.20-, 3.27-, 1.59-, and 2.65-fold of the control, respectively. The 14-deoxyandrographolide (NAD) in the host irrigated with MS was 3.35-fold that of the control. In addition, AP12-infected A. paniculata sterile seedlings could significantly increase ADC content and expression levels of key enzyme genes, especially on day 12, when the total lactone content of the host reached 88.881± 5.793 mg/g DW, while on day 6, CPS gene expression level reached 10.79-fold that of the control, in turn promoting the biosynthesis and accumulation of andrographolide. In conclusion, the endophytic fungus AP12 is beneficial to the growth and secondary metabolism of A. paniculata, which is helpful for the cultivation and application of the biological bacterial fertilizer in A. paniculata, providing a theoretical and research basis for the use of endophytic fungi as a microbial resource to improve the quality and yield of medicinal plants.

Fecal microbiota transplantation inhibits colorectal cancer progression: Reversing intestinal microbial dysbiosis to enhance anti-cancer immune responses.

Many lines of evidence demonstrate the associations of colorectal cancer (CRC) with intestinal microbial dysbiosis. Recent reports have suggested that maintaining the homeostasis of microbiota and host might be beneficial to CRC patients, but the underlying mechanisms remain unclear. In this study, we established a CRC mouse model of microbial dysbiosis and evaluated the effects of fecal microbiota transplantation (FMT) on CRC progression. Azomethane and dextran sodium sulfate were used to induce CRC and microbial dysbiosis in mice. Intestinal microbes from healthy mice were transferred to CRC mice by enema. The vastly disordered gut microbiota of CRC mice was largely reversed by FMT. Intestinal microbiota from normal mice effectively suppressed cancer progression as assessed by measuring the diameter and number of cancerous foci and significantly prolonged survival of the CRC mice. In the intestine of mice that had received FMT, there were massive infiltration of immune cells, including CD8+ T and CD49b+ NK, which is able to directly kill cancer cells. Moreover, the accumulation of immunosuppressive cells, Foxp3+ Treg cells, seen in the CRC mice was much reduced after FMT. Additionally, FMT regulated the expressions of inflammatory cytokines in CRC mice, including down-regulation of IL1a, IL6, IL12a, IL12b, IL17a, and elevation of IL10. These cytokines were positively correlated with Azospirillum_sp._47_25, Clostridium_sensu_stricto_1, the E. coli complex, Akkermansia, Turicibacter, and negatively correlated with Muribaculum, Anaeroplasma, Candidatus_Arthromitus, and Candidatus Saccharimonas. Furthermore, the repressed expressions of TGFb, STAT3 and elevated expressions of TNFa, IFNg, CXCR4 together promoted the anti-cancer efficacy. Their expressions were positively correlated with Odoribacter, Lachnospiraceae-UCG-006, Desulfovibrio, and negatively correlated with Alloprevotella, Ruminococcaceae UCG-014, Ruminiclostridium, Prevotellaceae UCG-001 and Oscillibacter. Our studies indicate that FMT inhibits the development of CRC by reversing gut microbial disorder, ameliorating excessive intestinal inflammation and cooperating with anti-cancer immune responses.

An Analysis of the Clinical Medication Rules of Traditional Chinese Medicine for Polycystic Ovary Syndrome Based on Data Mining.

Objective: The aim of the present study is to investigate the rules and characteristics of the clinical administration of traditional Chinese medicine (TCM) in the treatment of polycystic ovary syndrome (PCOS) using data mining methods. Method: Medical cases of well-known contemporary TCM doctors treating PCOS were collected from the China National Knowledge Infrastructure, Chinese Biomedical Literature Service System, Wanfang, Chinese Scientific Journals Database, and PubMed; the data were then characterized, and a standardized database of medical cases was built. This database was used to (1) count the frequency of syndrome types and the herbs used in medical cases by data mining methods and (2) analyze drug association rules and systematic clustering methods. Results: A total of 330 papers were included, involving 382 patients and a total of 1,427 consultations. The most common syndrome type was kidney deficiency; sputum stasis was the core pathological product and causative factor. A total of 364 herbs were used. Among them, 22 herbs were used >300 times, including Danggui (Angelicae Sinensis Radix), Tusizi (Semen Cuscutae), Fuling (Poria), Xiangfu (Nutgrass Galingale Rhizome), and Baizhu (Atractylodis Macrocephalae Rhizoma). Additionally, 22 binomial associations were obtained from the analysis of association rules; five clustering formulae were obtained via the analysis of high-frequency drug clusters; and 27 core combinations were obtained by k-means clustering of formula. Conclusion: In the treatment of PCOS, TCM is primarily employed as a combination approach involving tonifying the kidneys, strengthening the spleen, eliminating damp and dissolving phlegm, activating blood circulation, and resolving blood stasis. The core prescription is primarily a compound intervention based on the Cangfu Daotan pill, Liuwei Dihuang pill, and Taohong Siwu decoction.

Effect of acupoint stimulation on the anxiety of patients with breast cancer for intraoperative frozen section analysis.

BACKGROUND: The incidence of anxiety in patients with breast cancer is high, which seriously affects the physical and mental health of patients. OBJECTIVE: This study aimed to investigate the effect of acupoint stimulation on the anxiety of patients with breast cancer during operations and in the waiting period for intraoperative frozen section analysis. METHODS: Sixty patients with breast cancer experiencing anxiety who met the inclusion and exclusion criteria were randomly divided into the experimental group and the control group. The patients in the control group received routine nursing, and the patients in the experimental group were given acupoint stimulation on the basis of routine nursing. The HAMD scores, blood pressure readings, and heart rates were recorded before admission at one hour before the operation and in the waiting period for intraoperative frozen section analysis. RESULTS: The HAMD scores, blood pressure readings, and heart rates of the two groups showed an upward trend at all time points, and the differences were statistically significant. Compared with the control group, there were significant differences in indices detected at one hour before the operation and in the waiting period for intraoperative frozen section analysis. CONCLUSION: Acupoint stimulation therapy can effectively alleviate anxiety in patients with breast cancer.

Prenatal exposure to corn oil, CMC-Na or DMSO affects physical development and multi-organ functions in fetal mice.

Corn oil, sodium carboxymethyl cellulose (CMC-Na), and dimethyl sulfoxide (DMSO) are widely used as solvents or suspensions in animal experiments, but the effects of prenatal exposure to them on fetal development have not been reported. In this study, Kunming mice were given a conventional dose of corn oil (9.2 g/kg·d), CMC-Na (0.05 g/kg·d) or DMSO (0.088 g/kg·d) during gestation days 10-18, and the pregnancy outcome, fetal physical development, serum phenotype, and multi-organ function changes were observed. The results showed that corn oil decreased serum triglyceride level in males but increased their serum testosterone and CORT levels, and affected female placenta and female/male multi-organ functions (mainly bone, liver, kidney). CMC-Na increased female/male body lengths and tail lengths, decreased serum glucose and total cholesterol levels in males as well as increased their serum LDL-C/HDL-C ratio and testosterone level, decreased female serum bile acid level, and affected male/female placenta and multi-organ functions (mainly bone, liver, hippocampus). DMSO decreased male body weight and serum glucose level, decreased male/female serum bile acid levels, and affected male/female placenta and multi-organs functions (mainly bone, hippocampus, adrenal gland). In conclusion, prenatal exposure to a conventional dose of corn oil, CMC-Na or DMSO could affect fetal physical development and multi-organ functions, and has the characteristics of "multi-pathway, multi-organ and multi-target". This study provides the experimental basis for the rational selection of solvents or suspensions in pharmacology and toxicology studies.

Design, synthesis, and in vitro cytotoxicity evaluation of novel dihydroartemisinin-isatin hybrids tethered via different length of esters as potential anti-breast cancer agents.

In the present work, we reported the design, synthesis, and in vitro cytotoxicity evaluation of novel dihydroartemisinin-isatin hybrids tethered via different length of esters against MCF-7, MDA-MB-231, MCF-7/ADR and MDA-MB-231/ADR breast cancer cell lines. The preliminary results showed that the majority of the hybrids exhibited good anti-breast cancer cell activity. In particular, hybrids 7 g and 7n not only were more potent than ART, DHA and ADR against the four tested breast cancer cell lines, but also were non-toxic towards normal MCF-10A breast cells. The selectivity index values of hybrids 7 g and 7n were > 12.83 and > 25.97 respectively, revealing their excellent safety and selectivity profiles. The drug-resistant index values of hybrids 7 g and 7n were in a range of 0.33 to 1.12, implying that these hybrids had the potential to overcome drug resistance. Accordingly, hybrids 7 g and 7n could be considered as potential lead molecules for the development of novel anti-breast cancer agents with minimal untoward events to normal human cells. The structure-activity relationships indicated that the length of ester likner between DHA and isatin as well as substituents at C-3 and C-5 positions of isatin moiety had great impact on the activity.

Nutrient dynamics and microbial community response in macrophyte-dominated lakes: Implications for improved restoration strategies.

Although lakes dominated by macrophytes are conducive to ecological balance, this balance is easily disrupted by excessive nutrients flowing into the lake. However, knowledge of whether excessive nutrients lead to different microbial environmental vulnerabilities in the lake sediment between macrophyte-dominated areas and macrophyte-free areas is a prerequisite for the implementation of targeted protection measures. In this study, we investigated bacterial communities in sediments using high-throughput sequencing of 16S rRNA genes. Our results showed that the sources of total nitrogen (TN) and organic matter (OM) were related to the macrophytes. The structure, drivers, and interspecific associations of bacterial community, which were more susceptible to increased changes in TN and OM, differed significantly between macrophyte-dominated areas and macrophyte-free areas. More precisely, the lake edge, where was occupied by macrophytes, had a higher proportion of deterministic phylogenetic turnover (88.89%) than other sites, as well as a wider ecological niche and a tighter network structure. Further, as the difference in TN increased, the main assembly processes in surface sediments changed from stochastic to deterministic. However, the majority of phyla from the lake edge showed a greater correlation with excessive nutrients, and the selection of the community by excessive nutrients was more obvious at the edge of the lake. In addition, our results demonstrated that the stability of the bacterial community in macrophyte-free areas is greater than in macrophyte-dominated areas, while an excessively high deterministic process ratio and nutrient (TN and OM) concentration significantly reduced bacterial community stability at macrophyte-dominated areas. Taken together, these results provide a better understanding of the effects of excessive nutrients derived from macrophytes on bacterial community patterns, and highlight the importance of avoiding the accumulation of TN and OM in macrophyte-dominated areas to enhance the sustainability of the ecosystem after restoration of lakes with macrophytes.

Impact of prenatal amoxicillin exposure on hippocampal development deficiency.

BACKGROUND: Amoxicillin has been widely used to treat infectious diseases during pregnancy. Current studies suggest that amoxicillin exposure during pregnancy could lead to developmental disorders in the offspring and increase the incidence of long-term complications such as asthma and kidney damage in adulthood. However, the adverse effects of prenatal amoxicillin exposure (PAmE) including administration stage, doses and courses on fetal hippocampal neurodevelopment and its function in the offspring have not been elucidated. In this study, we intend to investigate the effects of PAmE on fetal hippocampal development and its possible mechanisms. METHOD: Pregnant Kunming mice were given intragastric administration with amoxicillin at different administration stage, doses and courses, and GD (gestational day) 18 offspring hippocampus was collected for morphological and development-related functional assays, and the molecular mechanisms were explored. RESULTS: PAmE induced hippocampal hypoplasia in the offspring with suppressed hippocampal neuronal cell proliferation and impaired neuronal synaptic plasticity comparatively; hippocampal astrocyte and microglia were damaged to varying degrees. The developmental toxicity of PAmE in fetal mices varies by time, dose, and course of treatment. The most severe damage was observed in the late gestation, high dose, and multi-course dosing groups. The significant reduction either in SOX2, an essential gene in regulating neural progenitor cell proliferation, and reduction of genes related to the Wnt/ß-catenin pathway may suggest that the key role of SOX2/Wnt/ß-catenin pathway in impaired hippocampal development in the offspring due to PAmE. CONCLUSION: In this study, PAmE was found to be developmentally toxic to the hippocampus thus to induce developmental damage to various hippocampal cells; Even with current clinically safe doses, potential hippocampal damage to offspring may still present; This study provides a theoretical and experimental basis for guiding the rational usage of drugs during pregnancy and giving effectively assessment of the risk on fetal hippocampal developmental toxicity.

Incorporation of probiotics into 3D printed Pickering emulsion gel stabilized by tea protein/xanthan gum.

Different xanthan gum (XG) concentrations on the rheological/texture properties of Pickering emulsion (PE) gel stabilized by tea protein/xanthan gum (TP/XG) were studied to achieve an ink feasible for 3D printing. Afterwards, the effects of 3D printing and digestion process on the viability of probiotics were studied when encapsulated in the PE gel. Results indicated that gel strength, stability, storage modulus (G') and loss modulus (G″) increased as XG concentration increased. Nozzle diameter and printing temperature of 45 and 55℃ had no significant effect on probiotic's viability, but printing temperature of 65℃ reduced viable probiotics from 8.07 to 6.59 log CFU/g. No significant change of probiotics viability in 3D printed samples was observed during 11-day storage at 4℃. PE gel encapsulated probiotic's viability was significantly improved under heat treatment and simulated gastrointestinal environment. This study gives insights on the production of 3D printed foods using PE gel incorporating probiotics.

Effect of Berberine on Activation of TLR4-NFκB Signaling Pathway and NLRP3 Inflammasome in Patients with Gout.

OBJECTIVE: To determine the effects of berberine (BBR) on the activation of toll-like receptor 4 (TLR4), nuclear factor (NF)κB (NF-κB) signaling and NLRP3 inflammasome in patients with gout. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from 24 acute (AP) and 41 non-acute (NAP) phases of primary gout patients, respectively, as well as 30 healthy controls (HC). TLR4, NF-κB (p65), NLRP3, apoptosis-associated specklike protein containing a CARD (PYCARD), cysteinyl aspartate specific proteinase-1 (CASP1), and interleukin-1ß (IL-1ß) mRNA expression levels in PBMCs were measured by quantitative reverse transcriptase polymerase chain reaction. The protein levels of TLR4, myeloid differentiation factor 88 (MyD88), NF-κB (p50/65), inhibitor of kappa B kinase α/ß (IKKα/ß), NF-κB inhibitor α (IKBα), phospho-IKKα/ß (p-IKKα/ß), NLRP3, PYCARD, and CASP1 were monitored by Western blotting. Serum IL-1ß protein level was measured using enzyme-linked immunosorbent assay (ELISA). In addition, PBMCs from HC and macrophages derived from a spontaneously immortalized monocyte-like cell line (THP-1) were stimulated using monosodium urate (MSU, 100 µg/mL), 0.1% dimethyl sulfoxide, 25 µmol/L BBR, and 10, 25, and 50 µmol/L BBR+100 µg/mL MSU for different time periods. The protein levels of IL-1ß and IL-18 in cell culture supernatants was measured by ELISA, and the protein expressions of TLR4, MyD88, NF-κB (p50/p65), IKKα/ß, I κBß, p-IKKα/ß, NLRP3, PYCARD, and CASP1 in macrophages were analyzed by Western blotting. RESULTS: (1) TLR4, NF-κB (p65), PYCARD, CASP1, and IL-1ß mRNA levels in PBMCs were significantly higher in the AP group than in the HC group (P<0.05). The NLRP3 mRNA expression levels in PBMCs were found to be significantly lower in the AP and NAP groups than in the HC group (P<0.05, P<0.01). (2) The protein levels of TLR4, IKKß, MyD88, NF-κB, p-IKKα/ß, PYCARD, and CASP1 in PBMCs were significantly higher, and those of IκBα, IKKα, and NLRP3 were found to be significantly lower in the AP group than in the HC group (P<0.05 or P<0.01). (3) The serum IL-1ß protein levels were significantly higher in the AP and NAP groups than in the HC group (P<0.01). (4) The IL-1ß protein level was significantly lower in the culture supernatants of the PBMCs stimulated with MSU for 3 and 6 h in the 25 and 50 µmoL/L BBR groups compared with that in the MSU group (P<0.01). (5) The protein levels of IL-1ß and IL-18 were also significantly lower in the culture supernatants of macrophages stimulated with MSU for 3 and 6 h in BBR groups compared with those in the MSU group (P<0.01). (6) The protein levels of TLR4, MyD88, NF-κB (p50, p65, p105), IKKα/ß, p-IκBα, p-IKKα/ß, PYCARD, and CASP1 were significantly differed between the macrophages stimulated with MSU for 0.5 and 6 h in BBR groups compared with those in the MSU group (P<0.05 or P<0.01). CONCLUSIONS: Activation of TLR4-NFκB signaling and NLRP3 inflammasome by MSU crystals drives the progression of gout inflammation. BBR ameliorates gouty inflammation, which is mechanistically associated with its regulation of TLR4-NF-κB signaling and NLRP3 inflammasome expression.

Vitamin D inhibits bone loss in mice with thyrotoxicosis by activating the OPG/RANKL and Wnt/ß-catenin signaling pathways.

Objective: Vitamin D and thyroid hormones have crucial roles in bone metabolism. This study aims to explore the effects of vitamin D on bone metabolism in mice with thyrotoxicosis and its mechanisms. Methods: 12-week-old mice were randomly divided into 6 groups (6 mice/group), the control (CON) group, vitamin D (VD) group, low-dose LT4 (Low LT4) group, low-dose LT4+VD (Low LT4+VD) group, high-dose LT4 (High LT4) group, high-dose LT4+VD (High LT4+VD) group, LT4 was provided every day and vitamin D3 every other day for 12 weeks. Thyroid function, 25-hydroxy vitamin D, type I collagen carboxy-terminal peptide (CTX), and type I procollagen amino-terminal peptide were determined. In addition, microcomputed tomography, bone histology and histomorphometry, a three-point bending test, and the mRNA expression of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL) and ß-catenin in bone were conducted. Results: The BMD of lumbar vertebrae and femur decreased and the bone microstructure was destroyed significantly in thyrotoxicosis mice. Addition of vitamin D improved the BMD and bone microstructure only in the low LT4+VD group. Mice with thyrotoxicosis had a significantly higher level of CTX (P<0.05), which was decreased by treatment with vitamin D (P<0.05). The eroded surface per bone surface (Er. S/BS) of the cancellous bone and elongated surface/endocortical perimeter (Er. S/E Pm) of the cortical bone significantly increased in the Low LT4 and High LT4 groups (P<0.05). Treatment with vitamin D significantly decreased the Er. S/BS and Er. S/E Pm. But, treatment with vitamin D did not significantly improve the toughness and rigidity of bones. The ratio of OPG to RANKL and mRNA expression of ß-catenin in the Low LT4+VD group were higher than that in the Low LT4 group (P<0.05). Conclusion: In mice with thyrotoxicosis, treatment with vitamin D can inhibit bone resorption and improve the BMD and trabecular bone architecture by increasing the ratio of OPG to RANKL and upregulating the expression of Wnt/ß-catenin.

Activation of farnesoid X receptor suppresses ER stress and inflammation via the YY1/NCK1/PERK pathway in large yellow croaker (Larimichthys crocea).

Unfolded protein responses from endoplasmic reticulum (ER) stress have been implicated in inflammatory signaling. The vicious cycle of ER stress and inflammation makes regulation even more difficult. This study examined effects of farnesoid X receptor (FXR) in ER-stress regulation in large yellow croakers. The soybean-oil-diet-induced expression of ER stress markers was decreased in fish with FXR activated. In croaker macrophages, FXR activation or overexpression significantly reduced inflammation and ER stress caused by tunicamycin (TM), which was exacerbated by FXR knockdown. Further investigation showed that the TM-induced phosphorylation of PERK and EIF2α was inhibited by the overexpression of croaker FXR, and it was increased by FXR knockdown. Croaker NCK1 was then confirmed to be a regulator of PERK, and its expression in macrophages is increased by FXR overexpression and decreased by FXR knockdown. The promoter activity of croaker NCK1 was inhibited by yin-yang 1 (YY1). Furthermore, the results show that croaker FXR overexpression could suppress the P65-induced promoter activity of YY1 in HEK293t cells and decrease the TM-induced expression of yy1 in macrophages. These results indicate that FXR could suppress P65-induced yy1 expression and then increase NCK1 expression, thereby inhibiting the PERK pathway. This study may benefit the understanding of ER stress regulation in fish, demonstrating that FXR can be used in large yellow croakers as an effective target for regulating ER stress and inflammation.

Effects of Yoga Intervention on Functional Movement Patterns and Mindfulness in Collegiate Athletes: A Quasi-Experimental Study.

High-quality movement patterns and high levels of mindfulness are thought to be beneficial in preventing sports injuries. Yoga is recommended in the field of athlete rehabilitation. This study investigated the effects of yoga intervention on functional movement patterns and mindfulness in collegiate athletes. It is a quasi-experimental study with a pre/post-test control design. The participants were divided into a yoga group and a control group. A Functional Movement Screen and the Mindful Attention Awareness Scale were used to assess participants' basic movement patterns and mindfulness before and after 12 weeks of yoga intervention (two classes per week, 90 min per class). The results show that the yoga group's FMS scores improved more compared to the control group [F(1,78) = 29.08, p < 0.001, ŋp2 = 0.27], and that the scores for the deep squat (ŋp2 = 0.4), shoulder mobility (ŋp2 = 0.17), and trunk stability pushup (ŋp2 = 0.36) improved substantially. The dysfunctional score ratio for deep squats (χ2 = 18.57, p < 0.001), shoulder mobility (χ2 = 26.90, p < 0.001), trunk stability pushup (χ2 = 17.07, p < 0.001), and rotatory stability (χ2= 38.29, p <0.001) decreased significantly compared with the control group, but there was no significant improvement in asymmetric movement patterns (χ2 = 0.75, p = 0.39). The mindfulness scores in the yoga group significantly exceeded those of the control group [F(1,78) = 13.56, p < 0.001, ŋp2 = 0.15]. These results suggest that yoga intervention can improve functional movement patterns and mindfulness levels, but further evidence is needed to determine whether yoga could positively influence sports injuries.

Association of low birthweight and small for gestational age with maternal ferritin levels: A retrospective cohort study in China.

Background: Birthweight have profound impacts on health status throughout lifetime, however, the relationship between maternal ferritin level in pregnancy and birthweight of the newborn remains controversial. Objective: This retrospective cohort research was to analyze the association between maternal ferritin levels during pregnancy with birthweight outcomes, primarily for low birthweight (LBW) and small for gestational age (SGA). Methods: Newborns weighing lower than 2,500 grams were defined as LBW. SGA is defined as birthweight lower than the 10th percentile of the distribution of newborns' birthweight of the same gestational age. Multivariable logistic regressions have been used to explore the association of maternal ferritin levels and birthweight related outcomes, in which the ferritin concentration was logarithm transformed in the model. We further used restricted cubic spline models to explore linear/non-linear dose-response manners of ferritin level and birthweight outcomes. Results: A total of 3,566 pregnant women were included in the study. In the results of the present study, we observed that maternal ferritin levels were linearly associated with the risk of LBW (p-trend = 0.005) and SGA (p-trend = 0.04), with the adjusted odds ratios (ORs) of 1.78 (95% CI 1.37-2.32) for LBW and 1.87 (95% CI 1.38-2.54) for SGA with an increase in Ln-ferritin concentrations per unit. The adjusted ORs across quartiles of ferritin levels were 2.14 (95% CI 1.03-4.47) for Quartile 2, 3.13 (95% CI 1.47-6.69) for Quartile 3, and 3.63 (95% CI 1.52-8.68) for Quartile 4 for LBW. The adjusted ORs of LBW and SGA among women using supplemental iron were 0.56 (95% CI 0.38, 0.85) and 0.65 (95% CI 0.40, 1.05) compared with non-users, respectively. Conclusions: Our findings found a linear dose-response relationship between ferritin levels and an increased risk of poor birthweight outcomes, suggesting that maternal ferritin level during pregnancy may provide an additional predictor for differentiating poor birthweight related outcomes. Further exploration should be conducted to ensure maternal ferritin thresholds and iron supplement doses.