Methyl donor diet attenuates intimal hyperplasia after vascular injury in rats.

Environmental factors, particularly dietary habits, play an important role in cardiovascular disease susceptibility and progression through epigenetic modification. Previous studies have shown that hyperplastic vascular intima after endarterectomy is characterized by genome-wide hypomethylation. The purpose of this study was to investigate whether methyl donor diet affects intimal hyperplasia and the possible mechanisms involved. Intimal hyperplasia was induced in SD rats by carotid artery balloon injury. From 8 d before surgery to 28 d after surgery, the animals were fed a normal diet (ND) or a methyl donor diet (MD) supplemented with folic acid, vitamin B12, choline, betaine, and zinc. Carotid artery intimal hyperplasia was observed by histology, the effect of MD on carotid protein expression was analyzed by proteomics, functional clustering, signaling pathway, and upstream-downstream relationship of differentially expressed proteins were analyzed by bioinformatics. Results showed that MD attenuated balloon injury-induced intimal hyperplasia in rat carotid arteries. Proteomic analysis showed that there were many differentially expressed proteins in the common carotid arteries of rats fed with two different diets. The differentially expressed proteins are mainly related to the composition and function of the extracellular matrix (EMC), and changes in the EMC can lead to vascular remodeling by affecting fibrosis and stiffness of the blood vessel wall. Changes in the levels of vasculotropic proteins such as S100A9, ILF3, Serpinh1, Fbln5, LOX, HSPG2, and Fmod may be the reason why MD attenuates intimal hyperplasia. Supplementation with methyl donor nutrients may be a beneficial measure to prevent pathological vascular remodeling after injury.

Causal association of polyunsaturated fatty acids with chronic pain: a two-sample Mendelian randomization study.

Background: Observational studies have indicated an association between polyunsaturated fatty acids (PUFAs) and chronic pain, but the potential causal link remains controversial. Here, we aimed to investigate whether a causal relationship exists between the concentration of circulating PUFAs and chronic pain as well as the direction of this association. Methods: We collected statistical data from relevant genome-wide association studies to explore the causal link between four PUFAs, along with the ratio of omega-6 fatty acids (FAs) to omega-3 FAs (omega-6:3 ratio), and chronic pain in eight specific body parts. We used the inverse-variance weighting (IVW) method for two-sample Mendelian randomization (MR) analysis and conducted supplementary analyses using four other methods (MR-Egger, weighted median, weighted mode, and simple mode). To verify the robustness of the MR study, we performed multiple sensitivity analyses. Results: The results revealed a negative correlation between omega-3 FAs [IVW, OR 95% CI: 0.952 (0.914, 0.991), p = 0.017] and docosahexaenoic acid (DHA) [IVW, OR 95% CI: 0.935 (0.893, 0.978), p = 0.003] with abnormal and pelvic pain. Furthermore, a positive correlation was observed between the omega-6:3 ratio [IVW, OR 95% CI: 1.057 (1.014, 1.101), p = 0.009] with abdominal and pelvic pain. Additionally, we found a negative correlation between omega-3 FAs [IVW, OR 95% CI: 0.947 (0.902, 0.994), p = 0.028] and lower back pain or sciatica. However, no causal relationship was found between the concentration of circulating PUFAs and pain in other body parts, including the face, throat and chest, joints, limbs, lower back, and gynecological parts. The robustness of these MR results was verified through multi-validity and retention method analyses. Conclusion: Our analysis suggests that higher circulating concentrations of omega-3 FAs and DHA and a lower omega-6:3 ratio are associated with a reduced risk of abdominal and pelvic pain. Additionally, a higher concentration of circulating omega-3 FAs is linked to a reduced risk of lower back pain and/or sciatica. These findings have major implications for the targeted prevention and treatment of chronic pain using PUFAs.

Differential Diagnosis of Intracranial Malignant Tumors Using MRI Based on Morphological Features and Signal Intensity Ratio of Lesions.

Objective: To investigate the clinical value of conventional MRI morphological features and signal intensity ratio in the differential diagnosis of intracranial malignant tumors (high-grade glioma (HGG), primary central nervous system Lymphoma (PCNSL) and single brain metastasis (BM). Methods: Retrospective analysis of 92 cases of HGG, 27 cases of PCNSL, and 35 cases of BM. MRI data in The General Hospital of Western Theater Command from August 2014 to December 2021, comparative analysis of morphological characteristics of tumors and lesion/normal brain parenchyma signal ratio (lesiontonormal parenchymaratio, LNR), five indexes were included T1WI signal ratio (LNRT1), T2WI signal intensity ratio (LNRT2), T2WI/T1WI signal ratio (LNRT2/T1), T1WI enhanced signal ratio (LNRT1CE) and contrast enhancement ratio (CER). The differential diagnostic performance was also assessed by subject operating characteristic (ROC) curves. Results: HGG, PCNSL, and BM were all seen more frequently in the supratentorial region, More than 50% of HGG mainly showed irregular morphology, intratumoral necrosis, cystic degeneration, peritumoral severe edema, cyclic uneven enhancement after enhancement, PCNSL significantly enhanced the main uniformity, necrosis cyst became rare, BM group showed uneven enhancement, no obvious specificity, and the differences in tumor morphology, peritumor edema, intratumor hemorrhage, necrotic cystic lesions, and enhancement patterns were statistically significant among the three (P < .05). PCNSL LNRT1 and its LNRT1CE (LNRT1: 0.558 ± 0.050, LNRT1CE: 1.637 ± 0.125) were significantly higher than those of HGG (LNRT1: 0.480 ± 0.077, LNRT1CE: 1.425 ± 0.160) and BM (LNRT1: 0.514 ± 0.120, LNRT1CE: 1.375 ± 0.122), while LNRT2 and LNRT2/T1 (LNRT2: 1.389 ± 0.086, LNRT2/T1: 2.511 ± 0.295) were significantly lower than those of HGG (LNRT2: 1.527 ± 0.191, LNRT2/T1: 3.263 ± 0.657), and BM (LNRT2: 1.504 ± 0.089, LNRT2/T1: 3.103 ± 0.830). There was no significant difference in CER among the three groups (P > .05). ROC curve analysis of LNRT1, LNRT2, LNRT1CE, and LNRT2/T1 could be used to discriminate PCNSL from HGG and BM, with LNRT1CE having the largest area under the curve of 0.873, sensitivity of 0.963 and specificity of 0.669. Conclusion: MRI lesion morphological features and signal intensity ratio are important for discriminating HGG from PCNSL and BM. As a quantitative parameter, tumor signal intensity ratio can provide an important supplement for subjective judgment, to improve the accuracy of tumor qualitative diagnosis and differential diagnosis.

Selenium regulates T cell differentiation in experimental autoimmune thyroiditis in mice.

Selenium (Se) is an essential trace element that plays an important role in thyroid physiology. Se supplementation can reduce levels of autoimmune thyroid antibodies, which may be beneficial in Hashimoto's thyroiditis (HT). However, the long-term benefits of Se supplementation for HT patients are controversial and there is no clear clinical evidence to support it, so further basic and clinical research is needed. The effect of Se on immune cells, especially T cells, in autoimmune thyroiditis (AIT) has not been elucidated. Here, we replicated a mouse model of experimental autoimmune thyroiditis (EAT) on a high-iodine diet and treated it with Se supplementation. At week 8 of the experiment, Se supplementation reduced the destruction of thyroid follicles and the infiltration rate of lymphocytes in EAT mice, and reversed the disturbance of peripheral blood thyroxine and thyroid autoantibody levels. Further examination revealed that Se had broad effects on T-cell subsets. Its effects include reducing the production of pro-inflammatory cytokines by Th1 cells, inhibiting the differentiation and production of cytokines by Th2 and Th17 cells, and upregulating the differentiation and production of cytokines by Treg cells. These changes help alleviate thyroid follicle damage during EAT. In conclusion, selenium supplementation has the potential to improve the prognosis of AIT by altering the subset differentiation and/or function of CD4+ T cells.

Functional divergence of CYP76AKs shapes the chemodiversity of abietane-type diterpenoids in genus Salvia.

The genus Salvia L. (Lamiaceae) comprises myriad distinct medicinal herbs, with terpenoids as one of their major active chemical groups. Abietane-type diterpenoids (ATDs), such as tanshinones and carnosic acids, are specific to Salvia and exhibit taxonomic chemical diversity among lineages. To elucidate how ATD chemical diversity evolved, we carried out large-scale metabolic and phylogenetic analyses of 71 Salvia species, combined with enzyme function, ancestral sequence and chemical trait reconstruction, and comparative genomics experiments. This integrated approach showed that the lineage-wide ATD diversities in Salvia were induced by differences in the oxidation of the terpenoid skeleton at C-20, which was caused by the functional divergence of the cytochrome P450 subfamily CYP76AK. These findings present a unique pattern of chemical diversity in plants that was shaped by the loss of enzyme activity and associated catalytic pathways.

A Phytophthora infestans RXLR effector AVR8 suppresses plant immunity by targeting a desumoylating isopeptidase DeSI2.

The potato's most devastating disease is late blight, which is caused by Phytophthora infestans. Whereas various resistance (R) genes are known, most are typically defeated by this fast-evolving oomycete pathogen. However, the broad-spectrum and durable R8 is a vital gene resource for potato resistance breeding. To support an educated deployment of R8, we embarked on a study on the corresponding avirulence gene Avr8. We overexpressed Avr8 by transient and stable transformation, and found that Avr8 promotes colonization of P. infestans in Nicotiana benthamiana and potato, respectively. A yeast-two-hybrid (Y2H) screen showed that AVR8 interacts with a desumoylating isopeptidase (StDeSI2) of potato. We overexpressed DeSI2 and found that DeSI2 positively regulates resistance to P. infestans, while silencing StDeSI2 downregulated the expression of a set of defense-related genes. By using a specific proteasome inhibitor, we found that AVR8 destabilized StDeSI2 through the 26S proteasome and attenuated early PTI responses. Altogether, these results indicate that AVR8 manipulates desumoylation, which is a new strategy that adds to the plethora of mechanisms that Phytophthora exploits to modulate host immunity, and StDeSI2 provides a new target for durable resistance breeding against P. infestans in potato.

The Combined Administration of Vitamin C and Copper Induces a Systemic Oxidative Stress and Kidney Injury.

Vitamin C (ascorbic acid; AA) and copper (Cu2+) are well used supplements with many health-promoting actions. However, when they are used in combination, the Fenton reaction occurs, leading to the formation of highly reactive hydroxyl radicals. Given that kidney is vulnerable to many toxicants including free radicals, we speculated that the in vivo administration of AA plus Cu2+ may cause oxidative kidney injury. The purpose of this study was to address this possibility. Mice were administered with AA and Cu2+, alone or in combination, via oral gavage once a day for various periods. Changes in the systemic oxidative status, as well renal structure and functions, were examined. The administration of AA plus Cu2+ elevated protein oxidation in serum, intestine, bladder, and kidney, as evidenced by the increased sulfenic acid formation and decreased level of free sulfhydryl groups (-SH). The systemic oxidative stress induced by AA plus Cu2+ was associated with a significant loss of renal function and structure, as indicated by the increased blood urea nitrogen (BUN), creatinine and urinary proteins, as well as glomerular and tubular cell injury. These effects of AA and Cu2+ were only observed when used in combination, and could be entirely prevented by thiol antioxidant NAC. Further analysis using cultured renal tubular epithelial cells revealed that AA plus Cu2+ caused cellular protein oxidation and cell death, which could be abolished by NAC and catalase. Moreover, coincubation of AA and Cu2+ led to H2O2 production. Collectively, our study revealed that a combined administration of AA and Cu2+ resulted in systemic oxidative stress and renal cell injury. As health-promoting supplements, AA and Cu2+ should not be used together.

Flavor components detection and discrimination of isomers in Huaguo tea using headspace-gas chromatography-ion mobility spectrometry and multivariate statistical analysis.

Aroma components are one of the crucial factors in dynamic processes analysis, quality control, and origin traceability. Various categories of Huaguo Tea possessed different taste due to the generation of aroma. In this study, a comprehensive analysis of volatiles was conducted for five popular Huaguo Tea samples (Lemon Slices, Bitter Gourd Slices, Citri Reticulatae Pericarpium, Red Lycium Barbarum, and Black Lycium Barbarum) via gas chromatography-ion mobility spectrometry (GC-IMS) combining with multivariate statistical strategies. Comparison analysis was achieved with the properties of visually and intuitively by drawing of topography plots. A total of one hundred and eighty volatiles were distinguished. Aliphatic isomers were identified simultaneously by fingerprint spectra. Alcohols, aldehydes, esters, and ketones were the most abundant volatiles in Huaguo Tea samples. To characterize the Huaguo Tea precisely and establish an analysis model for their classification, multivariate statistical analysis was applied to distinguish different Huaguo Tea. Satisfied discrimination was obtained by principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA) based on the HS-GC-IMS results with the robustness parameter (R2Y) of 99.4%, and prediction ability parameter (Q2) of 98.6%, respectively. The results provide a theoretical basis for aroma discrimination, isomer identification, and categories analysis of Huaguo Tea.

Panax ginseng Meyer cv. Silvatica phenolic acids protect DNA from oxidative damage by activating Nrf2 to protect HFF-1 cells from UVA-induced photoaging.

ETHNOPHARMACOLOGICAL RELEVANCE: Long-wave ultraviolet A (UVA) causes skin aging by damaging the fine structures of the skin, such as elastic fibers and collagen fibers, through oxidation. Currently, the use of plant extracts to protect skin from photoaging is a popular method. Panax ginseng C.A. Meyer exerts commendable anti-photoaging and antioxidant effects. P. ginseng Meyer cv. Silvatica, also known as forest ginseng (FG), is a type of ginseng cultivated by artificially simulating the growth environment of wild ginseng aged >15 years. However, there are only a few reports on its anti-photoaging effect on the skin caused by UVA stimulation. AIM OF THE STUDY: To investigate whether isolated and extracted FG can inhibit skin photoaging as well as to explore its action mechanism. METHODS: The FG extract (FGE) was obtained from the supernatant of FG after water extraction and alcohol precipitation with the D101 resin. The composition and content of phenolic acids in FGE were determined by high-performance liquid chromatography (HPLC). The MTT assay was performed to detect cell viability. The ratio of SA-ß-GAL-positive cells, CoL-I level, 8-OHdG concentration, MDA, GSH, GPx, SOD, and CAT activity were measured using relevant kits. Furthermore, cell cycle alterations and ROS accumulation were assessed by flow cytometry. The expressions of p53, p21, p16, and Keap1 protein were detected by Western blotting. The Nrf2 translocation was monitored by immunofluorescence staining. RESULTS: The findings revealed that FGE significantly restored UVA injury-induced cell viability, reduced the proportion of SA-ß-GAL-positive cells, and increased the level of CoL-I secretion in a dose-dependent manner, where the main ingredients were chlorogenic acid, protocatechuic acid, salicylic acid, p-hydroxybenzoic acid, vanillic acid, ferulic acid, and caffeic acid. Further studies indicated that this phenolic acid mixture (PAM) could alleviate UVA-induced HFF-1 cell cycle arrest and protect the DNA from oxidative damage caused by UVA stimulation. Moreover, the expressions of cell cycle regulatory proteins p53, p21, and p16 and the accumulation of ROS were inhibited, the translocation of Nrf2 into the nucleus was promoted, the expression of Keap1 protein was inhibited, the activity of intracellular antioxidant indicators GSH, GPx, SOD, and CAT was enhanced, and the expression of malondialdehyde (MDA) was inhibited. CONCLUSIONS: Collectively, our results demonstrated that FG phenolic acids protect DNA from oxidative damage by activating Nrf2 to safeguard the skin from photoaging induced by UVA stimulation.

Two new bis-diterpenoid alkaloids from Aconitum weixiense.

Further investigation on the roots of Aconitum weixiense led to the isolation of two new bis-diterpenoid alkaloids, named as weisaconitines E and F (1-2), which were elucidated by IR, HR-ESI-MS, 1D- and 2D-NMR analyses. Their structures are characterized as denudatine-atisine-type bis-diterpenoid alkaloids.

Meteorin links the bone marrow hypoxic state to hematopoietic stem/progenitor cell mobilization.

Hematopoietic stem/progenitor cells (HSPCs) are supported and regulated by niche cells in the bone marrow with an important characterization of physiological hypoxia. However, how hypoxia regulates HSPCs is still unclear. Here, we find that meteorin (Metrn) from hypoxic macrophages restrains HSPC mobilization. Hypoxia-induced factor 1α and Yin Yang 1 induce the high expression of Metrn in macrophages, and macrophage-specific Metrn knockout increases HSPC mobilization through modulating HSPC proliferation and migration. Mechanistically, Metrn interacts with its receptor 5-hydroxytryptamine receptor 2b (Htr2b) to regulate the reactive oxygen species levels in HSPCs through targeting phospholipase C signaling. The reactive oxygen species levels are reduced in HSPCs of macrophage-specific Metrn knockout mice with activated phospholipase C signaling. Targeting the Metrn/Htr2b axis could therefore be a potential strategy to improve HSPC mobilization for stem cell-based therapy.

Polydatin prevents lipotoxicity-induced dysfunction in pancreatic ß-cells by inhibiting endoplasmic reticulum stress and excessive autophagy.

BACKGROUND: Chronically elevated free fatty acid levels can adversely affect pancreatic ß-cells, leading to insulin resistance and eventually type 2 diabetes mellitus (T2DM). Polydatin (PD) from Polygonum cuspidatum has been shown to regulate blood lipid content and lower cholesterol levels. However, there have been no reports on the potential therapeutic effects and actions of PD on lipotoxicity in ß-cells. PURPOSE: This study aimed to investigate the protective effects of PD on palmitate (PA)-treated INS-1 insulinoma cells and diabetic mice. METHODS: Cells were incubated with PA and varying concentrations of PD for 24 h. Viability assays, morphological observations, flow cytometric analysis, western blotting, and reverse transcription-quantitative polymerase chain reaction were used to assess the effects of PD on PA-induced lipotoxicity. Western blotting was used to measure the endoplasmic reticulum stress (ERS) and the levels of autophagy-related factors after incubation with inducers and inhibitors of ERS and autophagy. Diabetic mice were treated with intragastric PD for 6 weeks followed by the measurement of their physiological and blood lipid indices and assessment of the results of histological and immunofluorescence analyses. RESULTS: Treatment with PD after PA exposure enhanced insulin secretion and the expression of diabetes-associated genes. PD promoted ß-cell function by reducing the levels of proteins associated with ERS and autophagy while also attenuating ERS triggered by tunicamycin. PD also reduced tunicamycin-induced autophagy, indicating that it regulated ERS-mediated autophagy and reduced PA-induced cellular dysfunction. In addition, treatment of db/db mice with PD substantially reduced body weight gain, alleviated dyslipidemia, improved ß-cell function, and reduced insulin resistance. CONCLUSION: These results suggest that PD protects ß-cells from lipotoxicity-induced dysfunction and apoptosis by inhibiting ERS and preventing excessive autophagy. Our study provides a new basis for exploring the potential of PD against ß-cell lipotoxicity and T2DM.

Identification of Abietane-Type Diterpenoids and Phenolic Acids Biosynthesis Genes in Salvia apiana Jepson Through Full-Length Transcriptomic and Metabolomic Profiling.

Salvia apiana (S. apiana) Jepson is a medicinal plant that is frequently used by the Chumash Indians in southern California as a diaphoretic, calmative, diuretic, or antimicrobial agent. Abietane-type diterpenoids (ATDs) and phenolic acids (PAs) are the main bioactive ingredients in S. apiana. However, few studies have looked into the biosynthesis of ATDs and PAs in S. apiana. In this study, using metabolic profiling focused on the ATDs and PAs in the roots and leaves of S. apiana, we found a distinctive metabolic feature with all-around accumulation of ATDs, but absence of salvianolic acid B. To identify the candidate genes involved in these biosynthesis pathways, full-length transcriptome was performed by PacBio single-molecule real-time (SMRT) sequencing. A total of 50 and 40 unigenes were predicted to be involved in ATDs and PAs biosynthesis, respectively. Further transcriptional profile using Illumina HiSeq sequencing showed that the transcriptional variations of these pathways were consistent with the accumulation patterns of corresponding metabolites. A plant kingdom-wide phylogenetic analysis of cytochromes (CYPs) identified two CYP76AK and two CYP76AH subfamily genes that might contribute for the specific ATDs biosynthesis in S. apiana. We also noticed that the clade VII laccase gene family was significantly expanded in Salvia miltiorrhiza compared with that of S. apiana, indicating their involvements in the formation of salvianolic acid B. In conclusion, our results will enable the further understanding of ATDs and PAs biosynthesis in S. apiana and Salvia genus.

Brown adipose tissue activation with ginsenoside compound K ameliorates polycystic ovary syndrome.

BACKGROUND AND PURPOSE: Polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disease affecting women of reproductive age. Due to its complex aetiology, there is no currently effective cure for PCOS. Brown adipose tissue (BAT) activity is significantly decreased in PCOS patients, and BAT activation has beneficial effects in animal models of PCOS. Here, we investigated the effect of ginsenoside compound K (CK) in an animal model of PCOS and its mechanism of BAT activation. EXPERIMENTAL APPROACH: Primary brown adipocytes, Db/Db mice and dehydroepiandrosterone (DHEA)-induced PCOS rats were used. The core body temperature, oxygen consumption, energy metabolism related gene and protein expression were assessed to identify the effect of CK on overall energy metabolism. Oestrous cycle, serum sex hormone, ovarian steroidogenic enzyme gene expression and ovarian morphology were also evaluated following CK treatment. KEY RESULTS: Our results indicated that CK treatment could significantly protect against body weight gain in Db/Db mice via BAT activation. Furthermore, we found that CK treatment could normalize hyperandrogenism, oestrous cyclicity, normalize steroidogenic enzyme expression and decrease the number of cystic follicles in PCOS rats. Interestingly, as a potential endocrine intermediate, C-X-C motif chemokine ligand-14 protein (CXCL14) was significantly up-regulated following CK administration. In addition, exogenous CXC14 supplementation was found to reverse DHEA-induced PCOS in a phenotypically similar manner to CK treatment. CONCLUSION AND IMPLICATIONS: In summary, CK treatment significantly activates BAT, increases CXCL14 expression and ameliorates PCOS. These findings suggest that CK might be a potential drug candidate for PCOS treatment.

The transcription factor StTINY3 enhances cold-induced sweetening resistance by coordinating starch resynthesis and sucrose hydrolysis in potato.

The accumulation of reducing sugars in cold-stored tubers, known as cold-induced sweetening (CIS), negatively affects potato processing quality. The starch to sugar interconversion pathways that are altered in cold-stored CIS tubers have been elucidated, but the mechanism that regulates them remains largely unknown. This study identified a CBF/DREB transcription factor (StTINY3) that enhances CIS resistance by both activating starch biosynthesis and repressing the hydrolysis of sucrose to reducing sugars in detached cold-stored tubers. Silencing StTINY3 in a CIS-resistant genotype decreased CIS resistance, while overexpressing StTINY3 in a CIS-sensitive genotype increased CIS resistance, and altering StTINY3 expression was associated with expression changes in starch resynthesis-related genes. We showed first that overexpressing StTINY3 inhibited sucrose hydrolysis by enhancing expression of the invertase inhibitor gene StInvInh2, and second that StTINY3 promoted starch resynthesis by up-regulating a large subunit of the ADP-glucose pyrophosphorylase gene StAGPaseL3, and the glucose-6-phosphate transporter gene StG6PT2. Using electrophoretic mobility shift assays, we revealed that StTINY3 is a nuclear-localized transcriptional activator that directly binds to the dehydration-responsive element/CRT cis-element in the promoters of StInvInh2 and StAGPaseL3. Taken together, these findings established that StTINY3 influences CIS resistance in cold-stored tubers by coordinately modulating the starch to sugar interconversion pathways and is a good target for improving potato processing quality.

Do you remember if you have olfactory dreams? A content analysis of LOFTER and a questionnaire survey conducted in China.

OBJECTIVES: Dreams often involve visual and auditory sensations, but olfactory experiences have not received the same amount of attention. This study explores the prevalence and content of olfactory dreams in China and investigates the relationship between olfactory imagery, olfactory significance, and olfactory dreamers. METHODS: In the first part of the study, 4302 dream records from LOFTER were screened and classified to preliminarily identify the prevalence and content of olfactory dreams. In the second part, 718 participants completed an online questionnaire about olfactory dreams, imagery, and significance. RESULTS: The prevalence of olfactory dreams in the diary dream entries and questionnaire survey participants were 3.95% and 18.70%, respectively. Instances in which odors appeared in dreams were more positive than negative and were mainly related to food, burning and smoke, body odor, nature, and certain environments and objects. Moreover, individuals with olfactory dreams showed better olfactory imagery, and stronger olfactory significance. CONCLUSIONS: Olfactory sensations occurred in the dreams of Chinese individuals, but their prevalence was very low. Most of the odors that emerged in these dreams were ones that the dreamers were familiar with in their daily lives.

BuFeiXiaoJiYin ameliorates the NLRP3 inflammation response and gut microbiota in mice with lung cancer companied with Qi-yin deficiency.

INTRODUCTION: NLRP3 inflammasome responses and gut microbiota have been shown an important role in lung cancer, however, the relationship between gut microbiota and NLRP3 inflammasome responses in lung cancer with Qi-yin deficiency remains elusive. METHODS: To investigate the effect of the traditional Chinese medicine BuFeiXiaoJiYin (BFXJY) on NLRP3 inflammasome responses and dysbiosis in lung cancer with Qi-yin deficiency, the female BALB/cA-nu mice were treated with LPS and ATP to induce inflammation, and were intragastrically treated with warm Chinese medicine and smoked with shavings to induce Qi-yin deficiency, as well as were injected with 1 × 107/ml A549 cells to simulate lung cancer. Then the three different doses of BuFeiXiaoJiYin (BFXJY) and positive control (CRID3) were used for intervention in mice for 27 consecutive days. Then, we estimated the protection effect of BFXJY on lung cancer mice with Qi-yin deficiency, through deterring tumor growth, NLRP3 inflammasome, PKC signaling, and homeostasis of gut microbiota. RESULTS: In this study, we found that BFXJY could inhibit the tumor growth in lung cancer with Qi-yin deficiency by reducing the production of IL-1ß and IL-18 and inhibiting NLRP3 inflammasome activation, which might be associated with the inhibition of PKC signaling. Furthermore, BFXJY could promote microbial diversity and balance the microbial composition changes induced by inflammation and Qi-yin deficiency in lung cancer. CONCLUSION: BuFeiXiaoJiYin ameliorates the NLRP3 inflammation response and gut microbiota in mice with lung cancer companied with Qi-yin deficiency. Our study provides a theoretical basis for the clinical development of therapeutic drugs targeting to treat lung cancer.

Ononin ameliorates inflammation and cartilage degradation in rat chondrocytes with IL-1ß-induced osteoarthritis by downregulating the MAPK and NF-κB pathways.

BACKGROUND: Osteoarthritis (OA) treatment aims to improve inflammation and delay cartilage degeneration. However, there is no effective strategy presently available. Ononin, a representative isoflavone glycoside component extracted from natural Chinese herbs, exerts anti-inflammatory and proliferative effects. However, the therapeutic effect of ononin on chondrocyte inflammation remains unclear. METHODS: In this study, we explored the therapeutic effect and potential mechanism of ononin in OA by establishing an interleukin-1 beta (IL-1ß)-induced chondrocyte inflammation model. RESULTS: Our results verified that ononin alleviated the IL-1ß-induced decrease in chondrocyte viability, attenuated the overexpression of the inflammatory factors tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6), and simultaneously inhibited the expression of cartilage extracellular matrix (ECM)-degrading enzymes such as matrix metalloproteinase-13 (MMP-13). Furthermore, the decomposition of Collagen II protein could be alleviated in the OA model by ononin. Finally, ononin improved chondrocyte inflammation by downregulating the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signalling pathways. CONCLUSION: Our findings suggested that ononin could inhibit the IL-1ß-induced proinflammatory response and ECM degradation in chondrocytes by interfering with the abnormal activation of the MAPK and NF-κB pathways, indicating its protective effect against OA.

[In vitro "benefit-risk" evaluation and network regulation mechanism of Colquhounia Root Tablets and its key material basis].

Colquhounia Root Tablets, prepared from Tripterygium, is effective for rheumatoid arthritis, diabetic nephropathy, and membranous nephropathy. However, the adverse reactions, such as liver injury, nausea, and vomiting, limit its application. This study aims to evaluate the advantages and risk of Colquhounia Root Tablets and its key active components in the treatment of rheumatoid arthritis, diabetic nephropathy, and membranous nephropathy and explore the potential mechanism in treating different diseases based on in vitro efficacy and toxicity assessment and biomolecular network analysis. First, the components of Colquhounia Root Tablets absorbed in blood were detected via ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry, and the influence of Colquhounia Root Tablets and its key components triptolide and celastrol on viability of human hepatocyte L02, human rheumatoid fibroblast-like synovial cell MH7 A, human renal tubular epithelial cell HK-2, and mouse podocyte MPC-5 was detected by cell counting kit 8(CCK8) assay. Then the expression of inflammatory cytokines of MH7 A and HK-2 cells was detected by enzyme-linked immunosorbent assay(ELISA). Moreover, the expression of nephrin and podocin in MPC-5 cells was measured by Western blot, and the expression of cytoskeletal protein by immunofluorence assay. Candidate targets of components from Colquhounia Root Tablets absorbed in blood were retrieved from TCMIP v2.0, and targets of the three diseases from GEO. The "disease-related genes-drug targets" network was constructed based on STRING, followed by pathway enrichment. Finally, molecular docking was performed by AutoDock Vina to explore the binding affinity of triptolide and celastrol with putative targets in the key signaling pathway. RESULTS:: showed that Colquhounia Root Tablets, triptolide, and celastrol can obviously reduce the levels of inflammatory cytokines in supernatant of MH7 A and HK-2 cells and enhance the expression of nephrin and podocin in MPC-5 cells. In addition, triptolide had the strongest toxicity to L02 cells, while Huobahuagen Tablets had the least toxicity to hepatocytes. Network analysis revealed that Colquhounia Root Tablets may intervene the three diseases through PI3 K/HIF1α/NOS signaling pathway. Both triptolide and celastrol had high binding affinities to corresponding targets in this signaling pathway. In conclusion, Colquhounia Root Tablets exerts similar effects on rheumatoid arthritis, diabetic nephropathy, and membranous nephropathy to triptolide and celastrol, but the toxicity was lower. PI3 K/HIF1α/NOS signaling pathway may be the common pathway of Colquhounia Root Tablets in the treatment of the three diseases.

Protective effect of oligosaccharides isolated from Panax ginseng C. A. Meyer against UVB-induced skin barrier damage in BALB/c hairless mice and human keratinocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Skin barrier dysfunction can lead to water and electrolyte loss, triggering homeostatic imbalances that can trigger atopic dermatitis and anaphylaxis. Panax ginseng C.A. Meyer is a traditional Chinese medicinal herb with known therapeutic benefits for the treatment of skin diseases, including photodamage repair effects and reduction of pigmentation. However, few reports exist that describe effectiveness of ginseng active components for repair of skin barrier damage. MATERIALS AND METHODS: Ginseng oligosaccharide extract (GSO) was prepared from P. ginseng via water extraction followed by ethanol precipitation and resin and gel purification. GSO composition and structural characteristics were determined using LC-MS, HPLC, FT-IR, and NMR. To evaluate GSO as a skin barrier repair-promoting treatment, skin of UVB-irradiated BALB/c hairless mice was treated with or without GSO then skin samples were evaluated for epidermal thickness, transepidermal water loss (TEWL), and stratum corneum water content. In addition, UVB-exposed skin samples and HaCaT cells were analyzed to assess GSO treatment effects on levels of epidermal cornified envelope (CE) protein and other skin barrier proteins, such as filaggrin (FLG), involucrin (IVL), and aquaporin-3 (AQP3). Meanwhile, GSO treatment was also evaluated for effects on UVB-irradiated hairless mouse skin and HaCaT cells based on levels of serine protease inhibitor Kazal type-5 (SPINK5), trypsin-like kallikrein-related peptidase 5 (KLK5), chymotrypsin-like KLK7, and desmoglein 1 (DSG1). These proteins are associated with UVB-induced skin barrier damage manifesting as dryness and desquamation. RESULTS: GSO was shown to consist of oligosaccharides comprised of seven distinct types of monosaccharides with molecular weights of approximately 1 kDa that were covalently linked together via ß-glycosidic bonds. In vivo, GSO applied to dorsal skin of BALB/c hairless mice attenuated UVB-induced epidermal thickening and moisture loss. Furthermore, GSO ameliorated UVB-induced reductions of levels of FLG, IVL, and AQP3 proteins. Additionally, GSO treatment led to increased DSG1 protein levels due to decreased expression of KLK7. In vitro, GSO treatment of UVB-irradiated HaCaT cells led to increases of FLG, IVL, and AQP3 mRNA levels and corresponding proteins, while mRNA levels of desquamation-related proteins SPINK5, KLK5, KLK7, and DSG1 and associated protein levels were restored to normal levels. CONCLUSION: A P. ginseng oligosaccharide preparation repaired UVB-induced skin barrier damage by alleviating skin dryness and desquamation symptoms, highlighting its potential as a natural cosmetic additive that can promote skin barrier repair after UVB exposure.