ABSTRACT
BACKGROUND: Curcubita ficifolia Bouché (Cucurbitaceae) has high value as a food crop and medicinal plant, and also has horticultural value as rootstock for other melon species. China is home to many different cultivars, but the genetic diversity of these resources and the evolutionary relationships among them, as well as the differences between C. ficifolia and other Cucurbita species, remain unclear. RESULTS: We investigated the chloroplast (cp) genomes of 160 C. ficifolia individuals from 31 populations in Yunnan, a major C. ficifolia production area in China. We found that the cp genome of C. ficifolia is ~151 kb and contains 128 genes, of which 86 are protein coding genes, 34 encode tRNA, and eight encode rRNAs. We also identified 64 SSRs, mainly AT repeats. The cp genome was found to contain a total of 204 SNP and 57 indels, and a total of 21 haplotypes were found in the 160 study individuals. The reverse repeat (IR) region of C. ficifolia contained a few differences compared with this region in the six other Cucurbita species. Sequence difference analysis demonstrated that most of the variable regions were concentrated in the single copy (SC) region. Moreover, the sequences of the coding regions were found to be more similar among species than those of the non-coding regions. The phylogenies reconstructed from the cp genomes of 61 representative species of Cucurbitaceae reflected the currently accepted classification, in which C. ficifolia is sister to the other Cucurbita species, however, different interspecific relationships were found between Cucurbita species. CONCLUSIONS: These results will be valuable in the classification of C. ficifolia genetic resources and will contribute to our understanding of evolutionary relationships within the genus Cucurbita.
Subject(s)
Cucurbita , Cucurbitaceae , Genome, Chloroplast , Humans , Cucurbita/genetics , Cucurbitaceae/genetics , Phylogeny , China , Chloroplasts/genetics , Genetic VariationABSTRACT
OBJECTIVES: To observe the effect of electroacupuncture (EA) on activation of silent information regulator 1 (Sirt1)/peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)/mitochondrial transcription factor A (TFAM) pathway in type 2 diabetes (T2DM) rats with peripheral neuropathy (DPN) , so as to explore its possible mechanisms underlying improvement of DPN. METHODS: Thirty male SD rats were randomly divided into blank control group (n=8) and DPN model group (n=22) which were further divided into model group (n=8) and EA group (n=8) after successful modeling. The model of T2DM was established by high-fat diet and low-dose intraperitoneal injection of streptozocin (35 mg/kg). For rats of the EA group (anesthetized with isoflurane), EA stimulation (2 Hz/15 Hz, 2 mA) was applied to "Tianshu"(ST25) for 20 min, once daily, 6 times a week for 6 weeks. The blood glucose level, body weight, area under curve (AUC) of glucose tolerance test, and hind-paw mechanical pain threshold and thermal pain threshold were observed. The intra-epidermal nerve fiber density (IENFD) of the hind-foot pad was observed by immunofluorescence staining. The motor nerve conduction velocity (MNCV) of the sciatic nerve was measured by using electrophysiological method. H.E. staining was used to observe the histopathological changes of the sciatic nerve after modeling. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes of the sciatic nerve. The protein expressions of energy-related Sirt1, PGC-1α and TFAM in the sciatic nerve was detected by Western blot. RESULTS: Compared with the blank control group, the model group had a higher blood glucose contents and AUC (P<0.001), a slower MNCV (P<0.01), and a decrease in the body weight and in the mechanical and thermal pain thresholds (P<0.001) and IENFD (P<0.001), and in the expression levels of Sirt1, PGC-1α and TFAM (P<0.05, P<0.01). In contrast to the model group, the EA group had a decrease in the blood glucose contents and AUC (P<0.05, P<0.01), and an increase in mechanical and thermal pain thresholds, MNCV, IENFD, and expression levels of Sirt1, PGC-1α and TFAM proteins (P<0.01, P<0.05). In addition, results of histopathological and ultrastructural changes of the sciatic nerve showed more fragmented and disordered distribution of axons on the transverse section, and extensive separation of myelin and axons, uneven myelin thickness, axonal degeneration and irregular shape in the model group, whereas in the EA group, the axons on the transverse section were relatively more dense and more complete, the myelin sheath of the sciatic nerve was relatively uniform, and the axonal shape was relatively regular with relatively milder lesions. CONCLUSIONS: EA up-regulates the expressions of Sirt1, PGC-1α, TFAM in T2DM rats with DPN, which may be associated with its functions in improving and repairing the injured peripheral nerves in rats with DPN.
Subject(s)
Acupuncture Points , Diabetes Mellitus, Type 2 , Electroacupuncture , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Sirtuin 1 , Animals , Humans , Male , Rats , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/therapy , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/genetics , Diabetic Neuropathies/therapy , Diabetic Neuropathies/metabolism , Diabetic Neuropathies/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Mitochondrial Proteins/metabolism , Mitochondrial Proteins/genetics , Peripheral Nervous System Diseases/therapy , Peripheral Nervous System Diseases/metabolism , Peripheral Nervous System Diseases/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Rats, Sprague-Dawley , Sciatic Nerve/metabolism , Sirtuin 1/metabolism , Sirtuin 1/genetics , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
To elucidate the effect of starch granule-associated proteins (SGAPs) on retrogradation properties of buckwheat starch, the retrogradation properties of Tartary buckwheat starch (TBS) and common buckwheat starch (CBS) before and after removal of SGAPs were systematically investigated, with wheat starch (WS) as reference. A significant decrease in gel strength of starches and density of starch aggregates were observed after removing SGAPs. The results were in line with the changes in retrogradation enthalpy of starches and short-range ordered structure of starch aggregates. After removing SGAPs, the retrogradation enthalpy of TBS decreased from 4.16 J/g to 3.74 J/g, CBS decreased from 4.05 J/g to 3.35 J/g and WS decreased from 3.27 J/g to 2.81 J/g, respectively. Taken together the results of LF-NMR, FTIR and rheological analysis, it can be concluded that SGAPs could promote the hydrogen bond interactions between starch molecules by competitively binding with water molecules, enhancing the rearrangement of starch molecules and forming a more ordered structure. Overall, the study suggested that the presence of SGAPs could enhanced the interaction between starch molecules chains, thus accelerated the retrogradation process. The research results provide more information about SGAPs in buckwheat starch and support further study for manipulation of starch properties.
Subject(s)
Fagopyrum , Starch , Starch/chemistry , Fagopyrum/chemistry , Plant Proteins/chemistry , ThermodynamicsABSTRACT
Introduction: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) contributes to a poor prognosis. Reliable biomarkers to predict adverse outcomes during hospitalization are important. Aim: To investigate the relationship between the serum cholinesterase (ChE) level and adverse clinical outcomes, including hypoxemia severity, hypercapnia, duration of hospital stay (DoHS), and noninvasive ventilation (NIV) requirement, in patients with AECOPD. Methods: Patients hospitalized with AECOPD in the Wuhu Hospital of Traditional Chinese Medicine between January 2017 and December 2021 were included. Results: A total of 429 patients were enrolled. The serum ChE level was significantly lower in patients with hypercapnia, who required NIV during hospitalization and who had a DoHS of >10 days, with an oxygenation index < 300. The ChE level was correlated negatively with the C-reactive protein level and neutrophil-to-lymphocyte ratio and correlated positively with the serum albumin level. Multivariate logistic regression analysis indicated that a serum ChE level of ≤4116 U/L (OR = 2.857, 95% CI = 1.46-5.58, p = 0.002) was associated significantly with NIV requirement. Conclusions: The serum ChE level was correlated significantly with complicating severe hypoxemia, hypercapnia, prolonged DoHS, and the need for NIV in patients hospitalized with AECOPD. The serum ChE level is a clinically important risk-stratification biomarker in patients hospitalized with AECOPD.
Subject(s)
Hypercapnia , Pulmonary Disease, Chronic Obstructive , Humans , Prognosis , Hypercapnia/complications , Cholinesterases , Pulmonary Disease, Chronic Obstructive/complications , Hypoxia/complications , Disease Progression , Retrospective StudiesABSTRACT
Pancreatic adipose tissue serves as a crucial structural basis for the development of glycolipid metabolic disorders. Understanding the mechanisms underlying pancreatic adipose tissue infiltration and regulatory strategies is essential for early intervention in glycolipid metabolic disorders. Pancreatic adipose tissue functions as a significant medium linking systemic immune metabolism, while the pancreatic vascular system emerges as a novel target for sensing pancreatic immune responses and maintaining the body's energy homeostasis, collectively participating in the development of glycolipid metabolic disorders. Acupuncture possesses potential effects in modulating the interaction between resident macrophages and adipocytes in the pancreas, leading to the reversible reduction of excessive pancreatic adipose accumulation, with its action being vascular-dependent.
Subject(s)
Acupuncture Therapy , Metabolic Diseases , Humans , Adipose Tissue/metabolism , Adipocytes/metabolism , Pancreas , Metabolic Diseases/therapy , Metabolic Diseases/metabolismABSTRACT
OBJECTIVE: This study aims to investigate the causal relationships between specific dietary habits and the risk of gout, while identifying the mediators involved in these associations. METHODS: We initially assessed the causal effects of five dietary habits on gout by two-sample Mendelian randomization (MR). Subsequently, we identified mediators from five plasma metabolites by two-step MR, including urate, urea, sex hormone-binding globulin (SHBG), interleukin-18 (IL-18), and C-reactive protein (CRP). Next, we quantified the proportion of mediation effects by multivariable Mendelian randomization (MVMR). Last, we performed reverse MR analyses. Sensitivity analyses were conducted to enhance the robustness of our findings. RESULTS: Only coffee intake demonstrated a significant negative casual effect on gout (inverse variance weighted: OR = 0.444, p = 0.049). In two-step MR, coffee intake decreased urate and urea while increased SHBG levels, but did not affect IL-18 and CRP levels. Besides, urate and urea showed positive causal effects while SHBG exhibited a negative impact on gout. In mediation analysis, urate, urea, and SHBG respectively mediated 53.60%, 16.43%, and 4.81% of the total causal effect of coffee intake on gout. The three mediators collectively mediated 27.45% of the total effect. Reverse MR analyses suggested no significant reverse causal effects. Sensitivity analyses supported the reliability of our causal inferences. CONCLUSION: Coffee intake reduced gout risk by decreasing urate and urea while increasing SHBG levels in plasma. These findings accentuate the benefits of coffee intake for gout management. The mediators may provide a novel insight into potential therapeutic targets for gout prevention. Key Points ⢠This study determines the causally protective effect of coffee intake on gout. ⢠We reveal that coffee intake reduced the risk of gout by decreasing urate and urea while increasing SHBG levels in plasma. ⢠Identifying specific mediators in the causal pathway from coffee intake to gout provides valuable information for clinical interventions of gout.
Subject(s)
Coffee , Gout , Uric Acid , Humans , Interleukin-18 , Mendelian Randomization Analysis , Reproducibility of Results , UreaABSTRACT
Brucine is a weak alkaline indole alkaloid with wide pharmacological activities and has been identified to protect against rheumatoid arthritis (RA) process. Circular RNAs (circRNAs) are also reported to be involved in the pathogenesis of RA. Here, we aimed to probe the role and mechanism of Brucine and circ_0139658 in RA progression. The fibroblast-like synoviocytes of RA (RA-FLSs) were isolated for functional analysis. Cell proliferation, apoptosis, invasion, migration, as well as inflammatory response were evaluated by CCK-8 assay, EdU assay, flow cytometry, transwell assay, and ELISA analysis, respectively. qRT-PCR and western blotting analyses were utilized to measure the levels of genes and proteins. The binding between miR-653-5p and circ_0139658 or Yin Yang 1 (YY1), was verified using dual-luciferase reporter and RNA pull-down assays. Brucine suppressed the proliferation, migration, and invasion of RA-FLSs, and alleviated inflammation by reducing the release of pro-inflammatory factors and macrophage M1 polarization. RA-FLSs showed increased circ_0139658 and YY1 levels and decreased miR-653-5p levels. Circ_0139658 is directly bound to miR-653-5p to regulate YY1 expression. Brucine treatment suppressed circ_0139658 and YY1 expression but increased YY1 expression in RA-FLSs. Functionally, circ_0139658 overexpression reversed the suppressing effects of Brucine on RA-FLS dysfunction and inflammation. Moreover, circ_0139658 silencing alleviated the dysfunction and inflammation in RA-FLSs, which were reverted by YY1 overexpression. Brucine suppressed the proliferation, migration, invasion, and inflammation in RA-FLSs by decreasing YY1 via circ_0139658/miR-653-5p axis.
Subject(s)
Arthritis, Rheumatoid , MicroRNAs , Strychnine/analogs & derivatives , Synoviocytes , Humans , Synoviocytes/metabolism , Synoviocytes/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/metabolism , Inflammation/drug therapy , Inflammation/metabolism , Fibroblasts/metabolism , Cell Proliferation , Cells, Cultured , Apoptosis , YY1 Transcription Factor/genetics , YY1 Transcription Factor/metabolismABSTRACT
A sustainable training system for acupuncture-moxibustion and tuina professionals, integrating "medicine, industry, education and research" is established, under the main framework of the medicine-engineering interdiscipline, and with the consideration of the issues of medicine, the application of engineering technology, the thinking approaches of sciences, and the collaboration of business studies. It is the potential power to support the development of traditional medicine. Through analyzing the difficulties of the medicine-engineering interdiscipline of acupuncture specialty, and in association with the experiences of the early-stage development of the collaboration between medicine and engineering, the paper presents the cases of China's higher education reform and transformation under the background of "emerging medical education" so as to explore a replicable personnel training mode.
Subject(s)
Acupuncture Therapy , Acupuncture , Education, Medical , Moxibustion , Humans , Acupuncture/education , ChinaABSTRACT
OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Zhongwan" (CV 12) and "Zusanli" (ST 36) on gastric motility and explore the response time of the acupoints at different regions for regulating gastric motility and its neuromechanism. METHODS: Thirty-three SD rats were randomly divided into a normal group, a vagectomy group and a splanchnicotomy group, 11 rats in each one. Vagectomy and splanchnicotomy were operated in the rats of the vagectomy group and the splanchnicotomy group, respectively. In each group, EA was delivered at "Zhongwan" (CV 2) and "Zusanli"(ST 36) on the left successively (with disperse-dense wave, 2 Hz/15 Hz in frequency and 2 mA in intensity); and it was performed at one acupoint for 1 min. Using multiple physiological signal collecting system, the intragastric pressure was measured 1 min before EA and in 0 s to 60 s, 0 s to 30 s and 30 s to 60 s of EA in the rats of each group, separately. The change rate of intragastric pressure was calculated to compare the effect size among groups. RESULTS: 1) Compared with that before intervention, in the normal group, the intragastric pressure was dropped in 0 s to 60 s, 0 s to 30 s and 30 s to 60 s of EA at "Zhongwan" (CV 12) (P<0.01); and it was elevated in 0 s to 60 s and 30 s to 60 s of EA at "Zusanli" (ST 36) (P<0.01). 2) In 0 s to 60 s, 0 s to 30 s and 30 s to 60 s of EA at "Zhongwan" (CV 12), the intragastric pressure decreased when compared with that before intervention in both the vagectomy group and the splanchnicotomy group (P<0.01, P<0.05); and it increased in 0 s to 60 s, 0 s to 30 s and 30 s to 60 s of EA at "Zusanli" (ST 36) in the splanchnicotomy group (P<0.05). 3) Compared with the normal group, the inhibition effect size was reduced in 30 s to 60 s of EA at "Zhongwan" (CV 12) in the vagectomy group (P<0.01), and in 0 s to 30 s and 30 s to 60 s of EA at "Zhongwan" (CV 12) in the splanchnicotomy group (P<0.01). During EA at "Zhongwan" (CV 12) for 0 s to 30 s and 30 s to 60 s, the inhibition effect size was declined more obviously in the splanchnicotomy group when compared with that in the vagectomy group (P<0.01). The excitation effect size was dropped in the vagectomy group when EA at "Zusanli" (ST 36) for 30 s to 60 s compared with the normal group (P<0.01), while it increased during 0 s to 30 s in the splanchnicotomy group (P<0.05). Compared with that of the vagectomy group, the excitation effect size increased more remarkably in the splanchnicotomy group when EA at "Zusanli" (ST 36) for 0 s to 30 s and 30 s to 60 s (P<0.01). CONCLUSIONS: Electroacupuncture at the acupoints of different regions differ in the response time and neuromechanism for regulating gastric motility of normal rats. The response time at "Zhongwan" (CV 12) is short and the effect of this acupoint works fast within 30 s; while that at "Zusanli" (ST 36) is prolonged and the effect starts 30 s later. In 0 s to 30 s of EA, the effect of "Zhongwan" (CV 12) and "Zusanli" (ST 36) is predominated by the splanchnic nerve; and in 30 s to 60 s, the effect of "Zhongwan" (CV 12) may be co-innervated by the splanchnic nerve and the vagus nerve, and that of "Zusanli" (ST 36) only by the vagus nerve.
Subject(s)
Electroacupuncture , Animals , Rats , Rats, Sprague-Dawley , Reaction Time , Acupuncture Points , Vagus NerveABSTRACT
Brown and white adipose tissue mediate thermogenesis through the thermogenetic centre of the brain, but safe methods for activating thermogensis and knowledge of the associated molecular mechanisms are lacking. We investigated body surface electroacupuncture stimulation (ES) at ST25 (targeted at the abdomen) induction of brown adipose thermogenesis and the neural mechanism of this process. Inguinal white adipose tissue (iWAT) and interscapular brown adipose tissue (iBAT) were collected and the thermogenic protein expression levels were measured to evaluate iBAT thermogenesis capacity. The thermogenic centre activating region and sympathetic outflow were evaluated based on neural electrical activity and c-fos expression levels. iWAT sensory axon plasticity was analysed with whole-mount adipose tissue imaging. ES activated the sympathetic nerves in iBAT and the c-fos-positive cells induced sympathetic outflow activation to the iBAT from the medial preoptic area (MPA), the dorsomedial hypothalamus (DM) and the raphe pallidus nucleus (RPA). iWAT denervation mice exhibited decreased c-fos-positive cells in the DM and RPA, and lower recombinant uncoupling orotein 1 peroxisome proliferator-activated receptor, ß3-adrenergic receptor, and tyrosine hydroxylase expression. Remodelling the iWAT sensory axons recovered the signal from the MPA to the RPA and induced iBAT thermogenesis. The sympathetic denervation attenuated sensory nerve density. ES induced sympathetic outflow from the thermogenetic centres to iBAT, which mediated thermogenesis. iWAT sensory axon remodelling induced the MPA-DM-RPA-iBAT thermogenesis pathway.
Subject(s)
Electroacupuncture , Mice , Animals , Sympathetic Nervous System/physiology , Obesity/therapy , Obesity/metabolism , Adipose Tissue, White , Adipose Tissue, Brown/metabolism , Thermogenesis , Sense OrgansABSTRACT
This study investigates the therapeutic potential of electroacupuncture (EA) on obesity, focusing on its influence on autophagy and energy metabolism, utilizing a high-fat diet (HFD)-induced mouse model. Treatment with EA significantly reduces body weight, fat deposition, and lipid accumulation in HFD-fed mice. Additionally, EA effectively ameliorates metabolic imbalances, reducing blood glucose levels and plasma markers of liver function. At the molecular level, EA enhances the expression of thermogenesis-associated genes in brown adipose tissue and decreases p53 expression, suggesting a decrease in apoptosis. Autophagy in white adipose tissue is inhibited by EA, as demonstrated by the suppression of key autophagy-related proteins. Further experiments highlight the critical role of Sirtuin 3 (Sirt3) in EA's anti-obesity effects. Sirt3 supplementation combined with EA results in reduced body weight, fat deposition, and lipid accumulation, along with modulations in key metabolic indicators. Moreover, EA's modulatory effect on uncoupling protein 1 (Ucp1), Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α), and p53 is found to be Sirt3 dependent. In conclusion, EA exerts beneficial effects against obesity through Sirt3-dependent modulation of autophagy and energy metabolism, indicating a potential therapeutic approach for obesity and related metabolic disorders.
Subject(s)
Electroacupuncture , Sirtuin 3 , Mice , Animals , Sirtuin 3/genetics , Sirtuin 3/metabolism , Sirtuin 3/therapeutic use , Diet, High-Fat/adverse effects , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/therapeutic use , Obesity/therapy , Obesity/genetics , Obesity/metabolism , Body Weight , Autophagy/genetics , Lipids/therapeutic useABSTRACT
Long-term high-fat diet (HFD) in adolescents leads to impaired hippocampal function and increases the risk of cognitive impairment. Studies have shown that HFD activates hippocampal microglia and induces hippocampal inflammation, which is an important factor for cognitive impairment. Electroacupuncture stimulation (ES), a nerve stimulation therapy, is anti-inflammatory. This study explored its therapeutic potential and mechanism of action in obesity-related cognitive impairment. 4-week-old C57 mice were given either normal or HFD for 22 weeks. At 19 weeks, some of the HFD mice were treated with ES and nigericin sodium salt. The cognitive behavior was assessed through Morris water maze test at 23 weeks. Western blotting was used to detect the expression levels of pro-inflammatory molecules IL-1ß and IL-1R, synaptic plasticity related proteins synaptophysin and Postsynaptic Density-95 (PSD-95), and apoptotic molecules (Caspase-3 and Bcl-2), in the hippocampus. The number, morphology, and status of microglia, along with the brain-derived neurotrophic factorï¼BDNFï¼ content, were analyzed using immunofluorescence. ES treatment improved cognitive deficits in HFD model mice, and decreased the expressions of microglial activation marker, CD68, and microglial BDNF. Inhibition of proinflammatory cytokine, IL-1ß, and IL-1R promoted PSD-95 and synaptophysin expressions. Peripheral NLRP3 inflammasome agonist injections exacerbated the cognitive deficits in HFD mice and promoted the expressions of IL-1ß and IL-1R in the hippocampus. The microglia showed obvious morphological damage and apoptosis. Collectively, our findings suggest that ES inhibits inflammation, regulates microglial BDNF, and causes remodeling of hippocampal function in mice to counteract obesity-like induced cognitive impairment. Overexcitation of peripheral inflammasome complexes induces hippocampal microglia apoptosis, which hinders the effects of ES.
Subject(s)
Cognitive Dysfunction , Electroacupuncture , Mice , Animals , Synaptophysin/metabolism , Microglia/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Diet, High-Fat/adverse effects , Inflammasomes/metabolism , Cognitive Dysfunction/therapy , Cognitive Dysfunction/drug therapy , Obesity/metabolism , Hippocampus/metabolism , Inflammation/metabolism , Mice, Inbred C57BLABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Chuanxiong, the rhizome of Ligusticum chuanxiong Hort., is an ancient herbal medicine that has gained extensive popularity in alleviating migraines with satisfying therapeutic effects in China. As the major bioactive component of Chuanxiong, the essential oil also exerts a marked impact on the treatment of migraine. It is widely recognized that neuroinflammation contributes to migraine. However, it remains unknown whether Chuanxiong essential oil has anti-neuroinflammatory activity. AIM OF THE STUDY: To explore the anti-neuroinflammatory properties of Chuanxiong essential oil and its molecular mechanisms by network pharmacology analysis and in vitro experiments. MATERIALS AND METHODS: Gas chromatography-mass spectrometry (GC-MS) was used to identify the chemical components of Chuanxiong essential oil. Public databases were used to predict possible targets, build the protein-protein interaction network (PPI), and perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Moreover, cytological experiments, nitric oxide assay, enzyme-link immunosorbent assay, western blotting, and immunofluorescence assay were adopted to prove the critical signaling pathway in lipopolysaccharide (LPS)-induced BV2 cells. RESULTS: Thirty-six compounds were identified from Chuanxiong essential oil by GC-MS, and their corresponding putative targets were predicted. The network pharmacology study identified 232 candidate targets of Chuanxiong essential oil in anti-neuroinflammation. Furthermore, Chuanxiong essential oil was found to potentially affect the C-type lectin receptor, FoxO, and NF-κB signaling pathways according to the KEGG analysis. Experimentally, we verified that Chuanxiong essential oil could significantly reduce the overproduction of inflammatory mediators and pro-inflammatory factors via the NF-κB signaling pathway. CONCLUSION: Chuanxiong essential oil alleviates neuroinflammation through the NF-κB signaling pathway, which provides a theoretical foundation for a better understanding of the clinical application of Chuanxiong essential oil in migraine treatment.
Subject(s)
Ligusticum , Migraine Disorders , NF-kappa B , Lipopolysaccharides/toxicity , Network Pharmacology , Neuroinflammatory DiseasesABSTRACT
OBJECTIVES: To investigate the effect of manual acupuncture at "Shangjuxu"(ST37) on nerve growth factor(NGF)/phosphatidylinositol 3-kinase(PI3K)/transient receptor potential vanilloid 1(TRPV1) signaling pathway in rats with chronic visceral hyperalgesia of irritable bowel syndrome (IBS), so as to explore its underlying mechanism in treating IBS chronic visceral hyperalgesia. METHODS: IBS chronic visceral hyperalgesia model was established by colorectal dilation stimulation for 2 weeks for SD pups at 8 d after birth, which were fed until 8-week age after the stimulation. Then the verified successfully modeled adult rats were randomly divided into model, Shangjuxu, and non-acupoint groups, with 6 rats in each group, and 6 unmodeled rats were selected as normal group. On the next day of model evaluation, rats in the Shangjuxu group received acupuncture at right ST37 while rats in the non-acupoint group received acupuncture at the non-meridian and non-acupoint point in the right hypochondrium, both for 15 min, with manual twisting of mild reinforcing and reducing performed for 30 s at an interval of 5 min, once a day, for a total of 7 d. Abdominal withdrawal reflex(AWR) score was used to evaluate the degree of chronic visceral pain in rats. Western blot and real-time fluorescence quantitative PCR were used to detect the colonic protein and mRNA expressions of NGF, tropomyosin receptor kinase A (TrkA), PI3K and TRPV1. The positive expressions of PI3K and TRPV1 proteins in the colon of rats were detected by immunohistochemistry method. RESULTS: Compared with the normal group, AWR scores corresponding to 4 pressure levels of 20, 40, 60 and 80 mm Hg, mRNA and protein expressions of NGF, TrkA, PI3K and TRPV1 in colon tissue, and positive expressions of PI3K and TRPV1 in colon tissue were significantly increased(P<0.05) in the model group. After intervention, compared with the model group, rats in the Shangjuxu group had reduced AWR scores corresponding to 4 pressure levels of 20, 40, 60 and 80 mm Hg, lower colonic mRNA and protein expressions of NGF, TrkA, PI3K and TRPV1, and decreased positive expressions of PI3K and TRPV1 in colon tissue(P<0.05), while there were no significant differences in the above indexes of the non-acupoint group. CONCLUSIONS: Manual acupuncture at ST37 can alleviate IBS chronic visceral hyperalgesia in rat and its analgesic effect may be related to regulating NGF/PI3K/TRPV1 signaling pathway.
Subject(s)
Acupuncture Therapy , Irritable Bowel Syndrome , Visceral Pain , Animals , Rats , Hyperalgesia/genetics , Hyperalgesia/therapy , Hyperalgesia/metabolism , Irritable Bowel Syndrome/genetics , Irritable Bowel Syndrome/therapy , Irritable Bowel Syndrome/metabolism , Nerve Growth Factor/genetics , Phosphatidylinositol 3-Kinases/genetics , Rats, Sprague-Dawley , RNA, Messenger/metabolism , Visceral Pain/genetics , Visceral Pain/therapyABSTRACT
BACKGROUND: A growing number of studies have shown that Yin Yang 1 (YY1) promotes the development of multiple tumours. The purpose of the current study was to determine the mechanism by which YY1 mediates neuroendocrine differentiation of prostate cancer (NEPC) cells undergoing cellular plasticity. METHODS: Using the Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases, we bioinformatically analyzed YY1 expression in prostate cancer (PCa). Aberrant YY1 expression was validated in different PCa tissues and cell lines via quantitative reverse transcription polymerase chain reaction, western blotting, and immunohistochemistry. In vivo and in vitro functional assays verified the oncogenicity of YY1 in PCa. Further functional assays showed that ectopic expression of YY1 promoted cellular plasticity in PCa cells via epithelial-mesenchymal transition induction and neuroendocrine differentiation. RESULTS: Androgen deprivation therapy induced a decrease in YY1 protein ubiquitination, enhanced its stability, and thus enhanced the transcriptional activity of FZD8. Castration enhanced FZD8 binding to Wnt9A and mediated cellular plasticity by activating the non-canonical Wnt (FZD8/FYN/STAT3) pathway. CONCLUSIONS: We identified YY1 as a novel dysregulated transcription factor that plays an important role in NEPC progression in this study. We believe that an in-depth investigation of the mechanism underlying YY1-mediated disease may lead to improved NEPC therapies.
Subject(s)
Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/metabolism , Wnt Signaling Pathway/genetics , Androgen Antagonists , Yin-Yang , Cell Differentiation/genetics , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolismABSTRACT
The impact of Na2 CO3 on the properties of doughs and noodles containing 70% Tartary buckwheat flour was investigated. Low-field 1 H nuclear magnetic resonance showed the mobility of water in the doughs significantly declined with the addition content of alkali from 0% to 0.9%. Na2 CO3 promoted the transformation from free sulfhydryl groups to disulfide bonds in doughs because the sulfhydryl groups in cysteine preferred to form thiolate anion and then oxidate under alkaline conditions. As for non-covalent chemical interactions, a significant increase of hydrogen bonds and a decrease of hydrophobic interactions were observed after Na2 CO3 addition. Quantitative analysis of microstructure showed that more uniform and denser gluten networks with higher branching rate and shorter average protein length and width formed in the doughs with 0.3%-0.6% of Na2 CO3 . The aggregated glutenin macropolymer and enhanced protein structure led to significantly stronger tensile of Tartary buckwheat dough sheets, which could meet the demand of continuous processing in the factory. Dough with alkali had higher swelling power and pasting viscosities, contributing to higher water absorption, and improved textural attributes of cooked noodles. This study demonstrated the possibility of adding Na2 CO3 at a moderate level for promoting the sheeting, cooking, and eating properties of high Tartary buckwheat flour composite noodles.
Subject(s)
Fagopyrum , Flour , Flour/analysis , Fagopyrum/chemistry , Alkalies , WaterABSTRACT
BACKGROUND: Thin endometrium is considered suboptimal for embryo implantation, leading to compromised pregnancy rates without effective therapies. While some studies have reported promoted endometrial growth after a period of hyperbaric oxygen therapy (HBOT) in patients with intrauterine adhesion, there have been no reports in patients with resistant thin endometrium. The purpose of this study was to investigate the impact of HBOT on endometrium growth and pregnancy outcomes in patients with resistant thin endometrium during frozen embryo transfer (FET) treatments. METHODS: This prospective pre-post cohort study was conducted at a university-affiliated assisted reproductive medical center between October 2021 and December 2022. Patients who had experienced at least one canceled transfer cycle due to a thin endometrium(< 7 mm) on the endometrium transformation day, despite the use of standard therapies as well as adjuvant therapies, were enrolled in the study. Patients were assigned voluntarily to either the HBOT group or the concurrent control group. The HBOT group received daily HBOT for at least 10 days during the proliferative phase, in addition to the routine endometrium preparation methods and the concurrent control group underwent cycles without HBOT. Propensity score matching (PSM) was used to ensure comparability between the groups. Both self-control and case-control comparisons were conducted. The primary outcome measured was endometrial thickness (ET) on the day of endometrium transformation. Secondary outcomes included intrauterine pregnancy rate (IPR), embryo implantation rate (IR), miscarriage rate, and others. RESULTS: Patients in the HBOT group demonstrated a significantly thicker endometrial thickness on the day of endometrium transformation after undergoing therapy (5.76 ± 1.66 vs. 6.57 ± 1.23, P = 0.002). This improvement was accompanied by a decreased rate of cycle cancellations. Baseline parameters and endometrial thickness were comparable between the HBOT group and the concurrent control group during the cycle. The IPR was similar in patients who received cleavage-stage embryos (0.0% vs. 6.7%, P = 1.00), but significantly higher in patients in the HBOT group who received blastocysts (53.8% vs. 18.2%, P = 0.017). CONCLUSIONS: A period of HBOT prior to endometrium transformation contributes to increased endometrial thickness and facilitates blastocyst implantation in patients with resistant thin endometrium during FET treatments. TRIAL REGISTRATION: The trial was registered on the Chinese Clinical Trial Registry (registration no. ChiCTR2300072831, retrospectively registered).
Subject(s)
Hyperbaric Oxygenation , Female , Pregnancy , Humans , Cohort Studies , Prospective Studies , Endometrium , Embryo TransferABSTRACT
Objective: To evaluate the prognostic value of common clinical inflammatory and nutritional indicators before treatment in patients with non-small cell lung cancer in the real world. Method: A total of 5,239 patients with pathologically confirmed non-small cell lung cancer from 2011 to 2018 in the Affiliated Cancer Hospital of Xinjiang Medical University were selected. Their inflammatory and nutritional indicators (RDW, PDW, NLR, LMR, NMR, PLR, SII, PNI, TP, ALB, CYRFA21-1, CEA, CA125, NSE, α1-globulin, α2-globulin, ß1-globulin, ß2-globulin, and γ-globulin) before treatment were collected. From the total number, 1,049 patients were randomly sampled (18 to 20% of patients each year) and used as the validation set; the remaining 4,190 patients were used as the training set. According to the eighth edition of the guidelines for the diagnosis, treatment, and stage risk stratification of lung cancer, the patients were divided into four groups: stage I/II operable, stage III operable, stage III inoperable, and stage IV. We used the X-tile software to intercept and classify the cut-off values of each index in the validation set. Univariate and multivariate Cox proportional-hazard regression were used to screen the independent risk factors affecting the prognosis of non-small cell lung cancer and establish a prognostic model for 1, 3, and 5 years. The validation set was used to verify its performance. Finally, the Kaplan-Meier curve was used to assess the survival rate, and the corresponding nomogram was established for clinical use. Results: After screening, no effective indicators were found in the stage I/II operable group. RDW and CA125 were effective indicators for the stage III operable group (cut-off values were 14.1 and 9.21, respectively, compared with the low-value group; univariate HR was 2.145 and 1.612, and multivariate HR was 1.491 and 1.691, respectively). CYRFA21-1 and CA125 were effective prognostic indicators for the stage III inoperable group (cut-off values were 10.62 and 44.10, respectively, compared with the low-value group; univariate HR was 1.744 and 1.342, and multivariate HR was 1.284 and 1.304, respectively). CYRFA21-1, CA125, NLR, and α1-globulin were effective indicators of prognosis in stage IV (cut-off values were 3.07, 69.60, 4.08, and 5.30, respectively, compared with the low-value group; univariate HR was 1.713, 1.339, 1.388, and 1.539; and multivariate HR was 1.407, 1.119, 1.191, and 1.110, respectively). The model was constructed with the best validation power in stage IV patients (C-index = 0.733, 0.749, and 0.75 at 1, 3, and 5 years, respectively). Conclusion: For patients with stage III and IV non-small cell lung cancer, some inflammatory markers, serum tumor markers, and nutritional indicators are independent prognostic factors. Combined with the general data of patients, the constructed prognostic evaluation model has the best efficacy in patients with stage IV and can be widely used in clinical practice.
ABSTRACT
On June 13, 2020, a liquefied petroleum gas tanker exploded in Wenling. Here, the authors describe the mass casualty emergency response to the explosion. The authors collected the medical records of 176 inpatients at 8 hospitals in Taizhou and Hangzhou. The 176 inpatients with blast injuries comprised 70 females and 106 males, with an average age of 45.48 ± 19.96 years, and more than half of the patients were farmers. They were transported to six hospitals distributed around the explosion site in Taizhou in the initial rescue period and were grouped according to their new injury severity score as having mild, moderate, severe, or extremely severe injuries. Most patients with severe and extremely severe injuries were admitted to a superior hospital for postsecondary triage. Forty-four patients experienced primary blast injuries, 137 experienced secondary blast injuries, 37 experienced tertiary blast injuries, and 40 patients experienced quaternary blast injuries. Multiple blast injuries were suffered by 62 patients. Most patients (95.45%) suffered external injuries, with the chest, extremities, and face as the main affected areas. Burns were diagnosed in 26 adults, of whom 15.38%, 19.23%, 7.70%, and 57.69% suffered mild, moderate, severe, and extremely severe cases. Sixteen burn patients suffered from burn-blast injuries. Upper limbs and the head/face/neck area, as exposed areas, were more likely to experience a burn injury. Inhalation was the main accompanying injury. Of the eight patients who died in the prehospital session, seven had burn injuries. This report on the accident and injury characteristics of an open-air LPG-related explosion will facilitate responses to subsequent catastrophes.
Subject(s)
Blast Injuries , Burns , Multiple Trauma , Petroleum , Adult , Male , Female , Humans , Middle Aged , Aged , Explosions , Burns/complications , Blast Injuries/complications , Triage , Retrospective StudiesABSTRACT
BACKGROUND: The best follow-up strategy for cancer survivors after treatment should balance the effectiveness and cost of disease detection while detecting recurrence as early as possible. Due to the low incidence of gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma [G-(MA)NEC], high-level evidence-based follow-up strategies is limited. Currently, there is a lack of consensus among clinical practice guidelines regarding the appropriate follow-up strategies for patients with resectable G-(MA)NEC. MATERIALS AND METHODS: The study included patients diagnosed with G-(MA)NEC from 21 centers in China. The random forest survival model simulated the monthly probability of recurrence to establish an optimal surveillance schedule maximizing the power of detecting recurrence at each follow-up. The power and cost-effectiveness were compared with the National Comprehensive Cancer Network, European Neuroendocrine Tumor Society, and European Society for Medical Oncology Guidelines. RESULTS: A total of 801 patients with G-(MA)NEC were included. The patients were stratified into four distinct risk groups utilizing the modified TNM staging system. The study cohort comprised 106 (13.2%), 120 (15.0%), 379 (47.3%), and 196 cases (24.5%) for modified groups IIA, IIB, IIIA, and IIIB, respectively. Based on the monthly probability of disease recurrence, the authors established four distinct follow-up strategies for each risk group. The total number of follow-ups 5 years after surgery in the four groups was 12, 12, 13, and 13 times, respectively. The risk-based follow-up strategies demonstrated improved detection efficiency compared to existing clinical guidelines. Further Markov decision-analytic models verified that the risk-based follow-up strategies were better and more cost-effective than the control strategy recommended by the guidelines. CONCLUSIONS: This study developed four different monitoring strategies based on individualized risks for patients with G-(MA)NEC, which may improve the detection power at each visit and were more economical, effective. Even though our results are limited by the biases related to the retrospective study design, we believe that, in the absence of a randomized clinical trial, our findings should be considered when recommending follow-up strategies for G-(MA)NEC.