Acupuncture alleviates inflammatory pain by activating CXCL1/CXCR2 signaling in the primary somatosensory cortex in adjuvant induced arthritis rats. / S1脑区CXCL1/CXCR2å‚ä¸Žé’ˆåˆºæ”¹å–„ä½å‰‚æ€§å ³èŠ‚ç‚Žå¤§é¼ ç‚Žæ€§ç—›çš„ä½œç”¨æœºåˆ¶.

OBJECTIVES: To observe whether acupuncture up-regulates chemokine CXC ligand 1 (CXCL1) in the brain to play an analgesic role through CXCL1/chemokine CXC receptor 2 (CXCR2) signaling in adjuvant induced arthritis (AIA) rats, so as to reveal its neuro-immunological mechanism underlying improvement of AIA. METHODS: BALB/c mice with relatively stable thermal pain reaction were subjected to planta injection of complete Freund adjuvant (CFA) for establishing AIA model, followed by dividing the AIA mice into simple AF750 (fluorochrome) and AF750+CXCL1 groups (n=2 in each group). AF750 labeled CXCL1 recombinant protein was then injected into the mouse's tail vein to induce elevation of CXCL1 level in blood for simulating the effect of acupuncture stimulation which has been demonstrated by our past study. In vivo small animal imaging technology was used to observe the AF750 and AF750+CXCL1-labelled target regions. After thermal pain screening, the Wistar rats with stable pain reaction were subjected to AIA modeling by injecting CFA into the rat's right planta, then were randomized into model and manual acupuncture groups (n=12 in each group). Other 12 rats that received planta injection of saline were used as the control group. Manual acupuncture (uniform reinforcing and reducing manipulations) was applied to bilateral "Zusanli" (ST36) for 4×2 min, with an interval of 5 min between every 2 min, once daily for 7 days. The thermal pain threshold was assessed by detecting the paw withdrawal latency (PWL) using a thermal pain detector. The contents of CXCL1 in the primary somatosensory cortex (S1), medial prefrontal cortex, nucleus accumbens, amygdala, periaqueductal gray and rostroventromedial medulla regions were assayed by using ELISA, and the expression levels of CXCL1, CXCR2 and mu-opioid receptor (MOR) mRNA in the S1 region were detected using real time-quantitative polymerase chain reaction. The immune-fluorescence positive cellular rate of CXCL1 and CXCR2 in S1 region was observed after immunofluorescence stain. The immunofluorescence double-stain of CXCR2 and astrocyte marker glial fibrillary acidic protein (GFAP) or neuron marker NeuN or MOR was used to determine whether there is a co-expression between them. RESULTS: In AIA mice, results of in vivo experiments showed no obvious enrichment signal of AF750 or AF750+CXCL1 in any organ of the body, while in vitro experiments showed that there was a stronger fluorescence signal of CXCL1 recombinant protein in the brain. In rats, compared with the control group, the PWL from day 0 to day 7 was significantly decreased (P<0.01) and the expression of CXCR2 mRNA in the S1 region significantly increased in the model group (P<0.05), while in comparison with the model group, the PWL from day 2 to day 7, CXCL1 content, CXCR2 mRNA expression and CXCR2 content, and MOR mRNA expression in the S1 region were significantly increased in the manual acupuncture group (P<0.05, P<0.01). Immunofluorescence stain showed that CXCR2 co-stained with NeuN and MOR in the S1 region, indicating that CXCR2 exists in neurons and MOR-positive neurons but not in GFAP positive astrocytes. CONCLUSIONS: Acupuncture can increase the content of CXCL1 in S1 region, up-regulate CXCR2 on neurons in the S1 region and improve MOR expression in S1 region of AIA rats, which may contribute to its effect in alleviating inflammatory pain.

Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

Shengjihuayu formula ameliorates the oxidative injury in human keratinocytes via blocking JNK/c-Jun/MMPs signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The reactive oxygen species (ROS) surge in the chronic wound tissue of diabetic ulcers (DUs) aggravates the inflammatory response. The oxidative stress state during inflammation will exacerbate inflammation and cause tissue damage, resulting in prolonged wound healing. Shengjihuayu Formula (SJHYF) is a renowned Chinese medicine prescription for treating chronic wounds in diabetic ulcers. Growing clinical evidence has demonstrated that SJHYF exhibits superior therapeutic efficacy and has a favorable safety profile. However, the underlying mechanisms by which SJHYF ameliorates oxidative damage under pathological conditions of DUs remain unclear. OBJECTIVE: To investigate the cytoprotective properties of SJHYF on hydrogen peroxide (H2O2)-induced cell damage in human HaCaT keratinocytes and to explore its potential targets and molecular pathways in treating DUs using RNA-seq. METHODS: HaCaT cells were incubated with H2O2 for 24 h to construct an oxidative stress cell model. Cell viability and proliferation were measured using the MTT and EdU assays, respectively. Cell migration was assessed using the scratch assay, and the fluorescence intensity of ROS was measured using the DCFH-DA probe. The chemical components of SJHYF were analyzed by UPLC-Q-TOF/MS, while the therapeutic effects of SJHYF on H2O2-induced HaCaT cells were analyzed using RNA-Seq. The potential target genes were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). At the same time, the pathway phenotype expression of SJHYF on the protection of H2O2-induced HaCaT cells was explored using Western Blot. RESULTS: The application of SJHY at a concentration of 0.25 mg/mL promoted cell proliferation, cell migration, and reduced ROS production. In addition, SJHYF was detected to have a total of 93 active compounds, including key components such as Galloyl-beta-D-glucose, Danshensu, Procyanidin B2, Catechin, and Alkannin. The RNA-seq analysis identified several core targets namely KRT17, TGM1, JUNB, PRDX5, TXNIP, PRDX1, HSP90AA1, HSP90AB1, HSPA8, and TNF-α. Western blot revealed the presence of the JNK/c-Jun/MMPs pathway and its related transcription factors. CONCLUSION: SJHYF displays significant protective effects on H2O2-induced oxidative cell damage in HaCaT cells via blocking the JNK/c-Jun/MMPs pathway.

Taraxacum: A Review of Ethnopharmacology, Phytochemistry and Pharmacological Activity.

Taraxacum refers to the genus Taraxacum, which has a long history of use as a medicinal plant and is widely distributed around the world. There are over 2500 species in the genus Taraxacum recorded as medicinal plants in China, Central Asia, Europe, and the Americas. It has traditionally been used for detoxification, diuresis, liver protection, the treatment of various inflammations, antimicrobial properties, and so on. We used the most typically reported Taraxacum officinale as an example and assembled its chemical makeup, including sesquiterpene, triterpene, steroids, flavone, sugar and its derivatives, phenolic acids, fatty acids, and other compounds, which are also the material basis for its pharmacological effects. Pharmacological investigations have revealed that Taraxacum crude extracts and chemical compounds contain antimicrobial infection, anti-inflammatory, antitumor, anti-oxidative, liver protective, and blood sugar and blood lipid management properties. These findings adequately confirm the previously described traditional uses and aid in explaining its therapeutic applications.

Analysis of the Potential Angiogenic Mechanisms of BuShenHuoXue Decoction against Osteonecrosis of the Femoral Head Based on Network Pharmacology and Experimental Validation.

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease with a high disability rate. The clinical effect of BuShenHuoXue decoction (BSHX) for ONFH is satisfactory. We aimed to elucidate the potential angiogenic mechanisms of BSHX in a rat femoral osteonecrosis model and bone marrow mesenchymal stem cells (BMSCs). METHODS: With in vivo experiments, we established the steroid-induced osteonecrosis of the femoral head (SONFH) model using Sprague-Dawley (SD) rats (8-week-old). The rats were randomly divided into five group of 12 rats each and given the corresponding interventions: control, model (gavaged with 0.9% saline), BSHX low-, medium- and high-dose groups (0.132 3, 0.264 6, and 0.529 2 g/mL BSHX solution by gavage). After 12 weeks, haematoxylin and eosin (H&E) staining was preformed to evaluate rat osteonecrosis. the expression of angiogenic factors (CD31, VEGFA, KDR, VWF) in rat femoral head was detected by immunohistochemistry, qPCR and western blotting. In cell experiment, BMSCs were isolated and cultured in the femoral bone marrow cavity of 4-week-old SD rats. BMSCs were randomly divided into eight groups and intervened with different doses of BSHX-containing serum and glucocorticoids: control group (CG); BSHX low-, medium-, and high-dose groups (CG + 0.661 5, 1.323, and 2.646 g/kg BSHX gavage rat serum); dexamethasone (Dex) group; and Dex + BSHX low-, medium-, and high-dose groups (Dex + 0.661 5, 1.323, and 2.646 g/kg BSHX gavaged rat serum), the effects of BSHX-containing serum on the angiogenic capacity of BMSCs were examined by qPCR and Western blotting. A co-culture system of rat aortic endothelial cells (RAOECs) and BMSCs was then established. Migration and angiogenesis of RAOECs were observed using angiogenesis and transwell assay. Identification of potential targets of BSHX against ONFH was obtained using network pharmacology. RESULTS: BSHX upregulated the expression of CD31, VEGFA, KDR, and VWF in rat femoral head samples and BMSCs (p < 0.05, vs. control group or model group). Different concentrations of BSHX-containing serum significantly ameliorated the inhibition of CD31, VEGFA, KDR and VWF expression by high concentrations of Dex. BSHX-containing serum-induced BMSCs promoted the migration and angiogenesis of RAOECs, reversed to some extent the adverse effect of Dex on microangiogenesis in RAOECs, and increased the number of microangiogenic vessels. Furthermore, we identified VEGFA, COL1A1, COL3A1, and SPP1 as important targets of BSHX against ONFH. CONCLUSION: BSHX upregulated the expression of angiogenic factors in the femoral head tissue of ONFH model rats and promoted the angiogenic capacity of rat RAOECs and BMSCs. This study provides an important basis for the use of BSHX for ONFH prevention and treatment.

Hydroxysafflor Yellow A Promotes HaCaT Cell Proliferation and Migration by Regulating HBEGF/EGFR and PI3K/AKT Pathways and Circ_0084443.

OBJECTIVE: To investigate the effect and possible mechanism of hydroxysafflor yellow A (HSYA) on human immortalized keratinocyte cell proliferation and migration. METHODS: HaCaT cells were treated with HSYA. Cell proliferation was detected by the cell counting kit-8 assay, and cell migration was measured using wound healing assay and Transwell migration assay. The mRNA and protein expression levels of heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF), EGF receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), and hypoxia-inducible factor-1α (HIF-1α) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Circ_0084443-overexpressing HaCaT cells and empty plasmid HaCaT cells were constructed using the lentiviral stable transfection and treated with HSYA. The expression of circ_0084443 was detected by qRT-PCR. RESULTS: HSYA (800 µmol/L) significantly promoted HaCaT cell proliferation and migration (P<0.05 or P<0.01). It also increased the mRNA and protein expression levels of HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α, and increased the phosphorylation levels of PI3K and AKT (P<0.05 or P<0.01). Furthermore, HSYA promoted HaCaT cell proliferation and migration via the HBEGF/EGFR and PI3K/AKT/mTOR signaling pathways (P<0.01). Circ_0084443 attenuated the mRNA expression levels of HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α (P<0.05). HSYA inhibited the circ_0084443 expression, further antagonized the inhibition of circ_0084443 on HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α, and promoted the proliferation of circ_0084443-overexpressing HaCaT cells (P<0.05 or P<0.01). However, HSYA could not influence the inhibitory effect of circ_0084443 on HaCaT cell migration (P>0.05). CONCLUSION: HSYA played an accelerative role in HaCaT cell proliferation and migration, which may be attributable to activating HBEGF/EGFR and PI3K/AKT signaling pathways, and had a particular inhibitory effect on the keratinocyte negative regulator circ_0084443.

The Therapeutic Effect of Laparoscopic Combined with Plasma Electric Cutting Knife on Patients with Rectal Cancer and its Impact on Serum Inflammatory Factors: A Retrospective Study.

Objective: This study investigated the therapeutic effect of laparoscopic surgery combined with the plasma electric cutting knife on patients diagnosed with rectal cancer and its impact on serum inflammatory factors in the bloodstream. Methods: The researchers examined the clinical data of 85 patients who underwent laparoscopic low anterior resection for rectal cancer in our hospital from April 2020 to December 2021. The patients comprised two groups: an observation group of 40 cases and a control group of 45 cases. The CD3+, CD4+, CD8+, and CD4+/CD8+ levels in both groups were detected using flow cytometry. The levels of relevant inflammatory factors in serum were measured using an automatic biochemical analyzer. The researchers then compared the perioperative outcomes between the two groups. Results: The observation group demonstrated significantly shorter duration for the first time passing gas after surgery (P = .029) and hospital stays (P = .002) than the control group. Both groups experienced decreased levels of CD8+ cells following treatment, with the observation group exhibiting lower levels than the control group (P < .05). After three months of treatment, both groups showed reduced levels of relevant serum inflammatory factors, TNF-α, IL-1, IL-6, and IL-8; however, the observation group was significantly lower than the control group with statistical significance (P < .05). Similarly, after three months of treatment, both groups exhibited lower levels of relevant serum electrolytes K+, Na+, and Cl-, with the observation group having lower levels than the control group (P < .05). Throughout the 12-month follow-up period, the two groups had no significant differences (P > .05) in complications such as urinary tract infection, anastomotic leakage, or anastomotic bleeding. Conclusion: Using a combination of laparoscopic techniques and a plasma electric cutting knife proved a highly effective surgical approach in treating rectal cancer. The method has numerous advantages, such as enhanced safety and few complications. When considering perioperative complications, it was evident that laparoscopic combined with the plasma electric cutting knife surpassed other surgical methods in treating rectal cancer.

Water extract of Pingchuan formula ameliorated murine asthma through modulating metabolites and gut microbiota.

BACKGROUND: Pingchuan formula is a traditional Chinese herbal prescription for asthma, but its components and underlying mechanisms remain unclear. Here, we evaluated its anti-asthmatic actvity and regulatory effects on the gut microbiota in mice based on the traditional Chinese medicine Zang-Fu theory, which proposed the exterior-interior relationship between the lung and the large intestine. METHODS: Mouse model withovalbumin (OVA)-induced asthma was used to assess the protective effect of the water extract of Pingchuan formula (PC). The chemical compounds of PC and mouse serum metabolites were identified by Ultraperformance liquid chromatography-Q Exactive HF-X spectrometry. Gut microbiota was evaluated by 16 S rRNA gene sequencing. The gut microbiota was depleted with a broad-spectrum antibiotic mixture (Abx) to explore whether it plays a role in the protective effects of PC. RESULTS: PC mainly contains phenols, flavonoids, alkaloids, carboxylic acids, and their derivatives. PC attenuated OVA-induced asthma in mice by alleviating inflammatory infiltration, indicated by decreased levels of IL-18, IL-6, IL-4, and Eotaxin in lung tissues. PC treatment altered the serum metabolites and affected the pyrimidine pathway. In addition, our results showed that acacetin and abscisic acid were the key serum metabolites PC treatment changed the composition of gut microbiota by increasing the relative abundance of Clostridia_UCG_014 and Akkermansia while decreasing Blautia, Barnesiella, and Clostridium_Ⅲ at the genus level. Importantly, the Abx treatment partly abolished the anti-asthmatic effect of PC. CONCLUSION: We demonstrated that PC could alleviate OVA-induced asthma in mice and protect against inflammatory infiltration in lungs via modulating the serum metabolites and gut microbiota, thereby providing a new reference for the therapeutic effect of PC.

The basic chemical substances of total alkaloids of Menispermi Rhizoma and their anti-inflammatory activities.

Menispermi Rhizoma is the dried rhizome of Menispermum dauricum DC. (Menispermaceae), which commonly used to treat sore throat, enteritis, and dysentery in traditional Chinese medicine. To clarify the chemical basis of the total alkaloids of M. Rhizoma, HPLC was used to analyze total alkaloids, and then representative chemical constituents were separated by tracking. Nineteen compounds, including two new alkaloids (1R-methymenidaurine A-α-N-oxide (1) and 1R-7'-hydroxymethyl-menidaurine A (2)), thirteen known alkaloids, and four known flavonoids were isolated and identified using spectroscopic methods. Meanwhile, seven characteristic peaks were identified from the total alkaloids using HPLC analysis. Furthermore, compounds 1-18 were screened in vitro for their inhibitory effect against nitric oxide production in BV-2 microglia cells stimulated by lipopolysaccharide. Among them, six compounds showed weak inhibition, and the IC50 values of compounds 1 and 2 were 56.87 ± 1.61 and 53.67 ± 1.52 mM, respectively.

Cynanchum komarovii extract for the treatment of rheumatoid arthritis by acting on synovial cells in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchum komarovii (CK), the northwest Chinese region's common medicinal herb, was traditionally utilized to treat arthritis, toothache, bald sores and cholecystitis. Various forms of arthritis can be treated with CK, based on "Medicinal Plants of Chinese Desert Areas". However, the exact mechanism of action in rheumatoid arthritis (RA) is uncertain. AIM OF THE STUDY: To evaluate the in vitro and in vivo effects of CK extracts on RA and to preliminarily investigate its anti-RA mechanism of action. MATERIALS AND METHODS: The main components of CK extract were analyzed by HPLC method. The effects of CK on the proliferation and apoptosis of human rheumatoid arthritis fibroblast-like synoviocytes (HFLS-RA) cells and the expression of apoptosis-related proteins in HFLS-RA cells were evaluated by CCK8 assay, flow cytometry and WB assay. To verify the anti-RA effect of CK extracts in vivo, a collagen-induced arthritis (CIA) rat model was established. The rats were divided into six groups: normal group, model group, CK high-dose group (1000 mg/kg, CK-H), CK medium-dose group (500 mg/kg, CK-M), CK low-dose group (250 mg/kg, CK-L) and methotrexate-positive drug group (MTX); the drug was administered continuously for 28 days. Body weight changes, joint swelling, arthritis index, bone density, ankle lesions, immune organ index, splenic lesions and inflammatory factor expression were used to evaluate the in vivo anti-RA activity of the extract. RESULTS: The findings of in vitro experiments showed that 10% CK-containing serum decreased the expression level of Bcl-2, increased the expression levels of Bax and Cleaved Caspase-3 in synovial cells, and prevented TNF-α induced aberrant proliferation and apoptotic antagonism in HFLS-RA cells. According to in vivo studies, CK extract at doses above 250 mg/kg was effective in controlling the levels of inflammatory factors, lowering the arthritis index, and improving foot swelling in CIA rats. When administered at doses up to 1000 mg/kg, CK extract significantly improved synovial lesions, increased bone density, and decreased abnormally elevated immune organ index in CIA rats. CONCLUSIONS: CK has significant anti-RA activity, and its anti-RA mechanism of action may be related to the regulation of the expression levels of apoptosis related proteins and the promotion of apoptosis in synovial cells.

[Effect of transcutaneous electrical acupoint stimulation combined with auricular acupressure on sexual hormone level and gonadal development in girls with precocious puberty].

OBJECTIVE: To explore the effect of transcutaneous electrical acupoint stimulation (TEAS) combined with auricular acupressure on serum sexual hormone level, and the ovarian, follicular and uterine development in the girls with precocious puberty. METHODS: Sixty girls with precocious puberty were randomly divided into a control group (30 cases, 2 cases dropped off) and a treatment group (30 cases, 3 cases dropped off). In both the control group and the treatment group, the healthy life-style intervention was provided for 12 weeks. Besides, in the treatment group, TEAS was delivered for 20 minutes each time, twice a week; and bilateral auricular acupressure was combined. The duration of treatment was 12 weeks. The levels of serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2), as well as ovarian volume, maximum follicular diameter and uterine volume before and after treatment were detected, and the safety was evaluated separately. RESULTS: Compared with before treatment, the contents of serum LH and FSH were increased (P<0.05), and the ovarian volume and the maximum follicle diameter were increased (P<0.05) in the control group after treatment; the contents of serum FSH and E2 were decresed (P<0.05), and the maximum follicular diameter was reduced significantly (P<0.05) in the treatment group after treatment. Compared with the control group, the contents of serum LH, FSH and E2 were decreased (P<0.05), while the ovarian volume and the maximum follicle diameter were decreased (P<0.05) in the treatment group after treatment. CONCLUSION: TEAS combined with auricular acupressure can effectively decrease the level of sex hormone, improve the ovarian and uterine development and retard the gonadal development. Such combined therapy is of high safety and conductive to regulating the development for the girls with precocious puberty.

Insights into the key quality components in Se-Enriched green tea and their relationship with Selenium.

Selenium-enriched green tea (Se-GT) is of increasing interest because of its health benefits, but its quality components obtained limited research. In this study, Enshi Se-enriched green tea (ESST, high-Se green tea), Pingli Se-enriched green tea (PLST, low-Se green tea), and Ziyang green tea (ZYGT, common green tea) were subjected to sensory evaluation, chemical analysis, and aroma profiling. Chemical profiles in Se-GT were consistent with the taste attributes of the sensory analysis. 9 volatiles were identified as key odorants of Se-GT based on multivariate analysis. Correlations between Se and quality components were further assessed and highly Se-related compounds contents in these three tea samples were compared. The results showed that most amino acids and non-gallated catechins were highly negatively correlated with Se, while gallated catechins exhibited strong positive correlation with Se. And there were strong and significant associations between the key aroma compounds and Se. Moreover, 11 differential markers were found between Se-GTs and common green tea, including catechin, serine, glycine, threonine, l-theanine, alanine, valine, isoleucine, leucine, histidine, and lysine. These findings provide great potential for quality evaluation of Se-GT.

HNRNPA2B1 as a potential therapeutic target for thymic epithelial tumor recurrence: An integrative network analysis.

Thymic epithelial tumors (TETs) are rare malignant tumors, and the molecular mechanisms of both primary and recurrent TETs are poorly understood. Here we established comprehensive proteomic signatures of 15 tumors (5 recurrent and 10 non-recurrent) and 15 pair wised tumor adjacent normal tissues. We then proposed an integrative network approach for studying the proteomics data by constructing protein-protein interaction networks based on differentially expressed proteins and a machine learning-based score, followed by network modular analysis, functional enrichment annotation and shortest path inference analysis. Network modular analysis revealed that primary and recurrent TETs shared certain common molecular mechanisms, including a spliceosome module consisting of RNA splicing and RNA processing, but the recurrent TET was specifically related to the ribosome pathway. Applying the shortest path inference to the collected seed gene module identified that the ribonucleoprotein hnRNPA2B1 probably serves as a potential target for recurrent TET therapy. The drug repositioning combined molecular dynamics simulations suggested that the compound ergotamine could potentially act as a repurposing drug to treat recurrent TETs by targeting hnRNPA2B1. Our study demonstrates the value of integrative network analysis to understand proteotype robustness and its relationships with genotype, and provides hits for further research on cancer therapeutics.

Mindfulness Practice versus Physical Exercise in Enhancing Vitality.

Vitality is important for subjective well-being and performance, which makes strategies for its enhancement an important research issue. While prior research showed that mindfulness practice and physical exercise are both effective at enhancing vitality, no study has compared their efficacy. This study aimed to address this issue. Seventy-one Chinese adults participated in the study and were randomized to one of the intervention groups, i.e., mindfulness practice or physical exercise. The mindfulness practice group completed guided mindfulness trainings, while the physical exercise group completed self-chosen aerobic trainings for seven days. The levels of vitality and its four factors at three time points (baseline, post-intervention, 7-day follow-up) were measured and compared. Compared with physical exercise, mindfulness practice showed stronger effects in enhancing vitality and maintaining the improvements. The findings suggest that guided mindfulness practice is more effective than self-chosen aerobic physical exercise at enhancing vitality and maintaining its improvements.

Crystal structure of tubulin-barbigerone complex enables rational design of potent anticancer agents with isoflavone skeleton.

BACKGROUND: Isoflavones possess many biological activities, including anti-inflammatory and anticancer effects. Microtubules (composed of αß-tubulin heterodimers) are described as one possible cellular target of some of these isoflavones. However, the binding of tubulin to isoflavones has not been extensively studied, and until now, no crystal structure of the tubulin-isoflavone complex has been solved, and details of the isoflavone-tubulin interaction remain elusive. PURPOSE: Barbigerone is an isoflavone mainly found in the genus Milletti, such as the edible leguminous plant Millettia ferruginea, with anticancer activity. This study aims to confirm the cellular target of barbigerone and to study its anticancer mechanism. METHOD: Surface plasmon resonance assays and X-ray crystallography were used to study the interaction of barbigerone with tubulin protein. Immunofluorescence, in-cell and in vitro tubulin polymerization assays were employed to investigate the mechanism. MTT assays, cell clonal formation assays, wound healing assays, tube formation assays and H460 xenograft models were conducted to evaluate the in vitro and in vivo anticancer activities of barbigerone and one of its derivatives, 0412. RESULTS: Here, we found that barbigerone binds to tubulin to inhibit tubulin polymerization. Moreover, we solved the X-ray crystal structure of the tubulin-barbigerone complex at 2.33 Å resolution, which unambiguously determined the orientation and position of barbigerone in the colchicine-binding site. Illuminated by the X-ray data, we synthetized and obtained a more active isoflavone, 0412. Both barbigerone and 0412 inhibit cancer cell proliferation, tubulin polymerization, migration of HeLa cells and capillary-like tube formation of HUVECs, induce G2/M phase cell cycle arrest and apoptosis, and exhibit anticancer activity in an H460 xenograft model. CONCLUSION: In all, through biochemical and X-ray crystal structure results, we identified tubulin as the cellular target of one isoflavone, barbigerone, and proved that the tubulin-barbigerone complex plays a guiding role in obtaining a more active compound, 0412. These studies provide a crucial research basis for the development of isoflavones as anticancer candidate compounds.

Ferroptosis: a new antidepressant pharmacological mechanism.

The incidence rate of depression, a mental disorder, is steadily increasing and has the potential to become a major global disability factor. Given the complex pathological mechanisms involved in depression, the use of conventional antidepressants may lead to severe complications due to their side effects. Hence, there is a critical need to explore the development of novel antidepressants. Ferroptosis, a newly recognized form of cell death, has been found to be closely linked to the onset of depression. Several studies have indicated that certain active ingredients can ameliorate depression by modulating the ferroptosis signaling pathway. Notably, traditional Chinese medicine (TCM) active ingredients and TCM prescriptions have demonstrated promising antidepressant effects in previous investigations owing to their unique advantages in antidepressant therapy. Building upon these findings, our objective was to review recent relevant research and provide new insights and directions for the development and application of innovative antidepressant strategies.

The autonomic nervous system: A potential link to the efficacy of acupuncture.

The autonomic nervous system (ANS) is a diffuse network that regulates physiological systems to maintain body homeostasis by integrating inputs from the internal and external environment, including the sympathetic, parasympathetic, and enteric nervous systems (ENS). Recent evidence suggests that ANS is one of the key neural pathways for acupuncture signal transduction, which has attracted worldwide attention in the acupuncture field. Here, we reviewed the basic and clinical research published in PubMed over the past 20 years on the effects of acupuncture on ANS regulation and homeostasis maintenance. It was found that acupuncture effectively alleviates ANS dysfunction-associated symptoms in its indications, such as migraine, depression, insomnia, functional dyspepsia, functional constipation. Acupuncture stimulation on some specific acupoints activates sensory nerve fibers, the spinal cord, and the brain. Using information integration and efferents from a complex network of autonomic nuclei of the brain, such as the insular cortex (IC), prefrontal cortex, anterior cingulate cortex (ACC), amygdala (AMG), hypothalamus, periaqueductal gray (PAG), nucleus tractus solitarius (NTS), ventrolateral medulla (VLM), nucleus ambiguus (AMB), acupuncture alleviates visceral dysfunction, inflammation via efferent autonomic nerves, and relieves pain and pain affect. The modulating pattern of sympathetic and parasympathetic nerves is associated with acupuncture stimulation on specific acupoints, intervention parameters, and disease models, and the relationships among them require further exploration. In conclusion, ANS is one of the therapeutic targets for acupuncture and mediates acupuncture's actions, which restores homeostasis. A systemic study is needed to determine the rules and mechanisms underlying the effects of acupoint stimulation on corresponding organs mediated by specific central nervous networks and the efferent ANS.

[Acupoit is the "transducer" in the physiochemical information coupling response of acupuncture].

Acupoint is the initial response site of acupuncture stimulus and also the source link of the effect onset of acupuncture. Acupuncture is a mechanical physical stimulus. How is the mechanical force of acupuncture transduced into neuroelectrical and biochemical signals at acupoint? How does the physiochemical information of acupoint launch acupuncture effect? All of these remain the common and crucial questions in the study of acupuncture effect mechanism. Physical changes are induced in the local tissue of acupoint by needling techniques, such as the deformation and displacement of muscle fibers, which may act on the nerve ending receptors and produce electroneurographic signals. Besides, these changes may activate the mechanosensitive ion channels of the cytomembrane in acupoint site. Through cellular signal transduction, the physical signals may be transformed into chemical ones to trigger the physiochemical coupling response of acupoint microenvironment. Eventually, acupuncture effect is generated via nerves and body fluids. "The mechanical force of acupuncture", through "the physiochemical transduction", promotes the body's perception and transmits acupuncture signals. It suggests that acupoint is the "transducer" in the physiochemical information coupling response of acupuncture.

Analysis of Placement Priorities and Nursing Countermeasures of Transnasally Inserted Intestinal Obstruction Catheters in Patients with Acute Small Bowel Obstruction.

Objective: To explore the placement priorities and analysis of nursing countermeasures of transnasally inserted intestinal obstruction catheters in patients with acute small bowel obstruction (ASBO). Methods: One hundred and three patients with ASBO treated in our hospital from May 2016 to February 2022 were enrolled to this study. Patients who received individual nursing for transnasally inserted intestinal obstruction catheters were considered as the observation group (n = 59) and those who received traditional nursing were regarded as the control group (n = 44). The symptom relief time, daily gastrointestinal decompression, bowel sound recovery time, exhaust, defecation recovery time, and gas-liquid plane disappearance time were compared between both groups. The abdominal pain was evaluated by visual analogue scale (VAS), and the psychology of patients was evaluated by self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Patients' clinical efficacy and incidence of adverse effects were counted, and quality of life was assessed using the short form 36 (SF-36) health survey questionnaire. Results: In the observation group, the improvement time of clinical symptoms and VAS, SAS, and SDS scores after intubation were lower than those of the control group, while the total clinical treatment efficiency was higher (P < 0.05). As to the adverse effects, the observation group was lower than the control group (P < 0.05). Also, the SF-36 scores were higher than those of the control group in all dimensions (P < 0.05). Conclusion: The individual nursing strategy implemented for the transnasally inserted intestinal obstruction catheter can effectively shorten the recovery of ASBO patients and improve their treatment outcome and prognosis quality of life.

Vitamin D and heart failure: A two-sample mendelian randomization study.

BACKGROUND AND AIMS: The relationship between vitamin D and heart failure (HF) has attracted significant interest, but the association between the two in previous studies remains uncertain. Therefore, we used two-sample Mendelian randomization (MR) to investigate a causal association between 25-hydroxyvitamin D (25OHD) and HF risk. METHODS AND RESULTS: This study utilized summary statistics from the most extensive genome-wide association studies for 25OHD and HF. To make the results more reliable, we used several methods based on three assumptions for MR analysis. We also used the multivariable MR adjusting for hypertension, BMI, diabetes, chronic kidney disease to further elucidate the association between 25OHD and HF. Considering the potential pleiotropy, we performed an MR analysis with conditionally independent genetic instruments at core genes to further determine the relationship between vitamin D and heart failure. We found that per 1 SD increase in standardized log-transformed 25OHD level, the relative risk of HF decreased by 16.5% (OR: 0.835, 95% Cl: 0.743-0.938, P = 0.002), and other MR methods also showed consistent results. The multivariable MR also reported that per 1 SD increase in standardized log-transformed 25OHD level, the relative risk of HF decreased. And the scatter plots showed a trend towards an inverse MR association between 25OHD levels, instrumented by the core 25OHD genes, and HF. CONCLUSION: In summary, we found a potential inverse association between elevated 25OHD levels and the risk of HF, which suggested that timely 25OHD supplementation or maintaining adequate 25OHD concentrations may be an essential measure for HF prevention in the general population.