ABSTRACT
A research strategy combining transcriptome data mining and experimental verification was adopted to identify the marker genes characterizing the syndrome elements of phlegm, stasis, and deficiency in steroid-induced osteonecrosis of the femoral head(SONFH). Firstly, the common differentially expressed gene sets of SONFH with the syndromes of phlegm-stasis obstructing collaterals, vessel obstruction, and liver-kidney deficiency were obtained from the clinical transcriptomic analysis of a previous study. The differential expression trend analysis and functional gene mining were then employed to predict the candidate marker gene sets representing phlegm, stasis, and deficiency. The whole blood samples from SONFH patients, whole blood samples from SONFH rats, and affected femoral head tissue samples were collected for qPCR, which aimed to determine the expression levels of the candidate marker genes mentioned above. Furthermore, the receiver operating characteristic curve(ROC) was established to objectively evaluate the syndrome differentiation effectiveness of the candidate marker genes mentioned above. The transcriptome data analysis results showed that the candidate marker genes for phlegm was ELOVL fatty acid elongase 6(ELOVL6), and those for stasis were ankyrin 1(ANK1), glycophorin A/B(GYPA/B), and Rh-associated glycoprotein(RHAG). The candidate marker genes for deficiency were solute carrier family 2 member 1(SLC2A1) and stomatin(STOM). The qPCR results showed that compared with that in the non-SONFH group, ELOVL6 had the lowest expression level in the peripheral blood of the SONFH patients with the syndrome of phlegm-stasis obstructing collaterals(P<0.05). Compared with that in the normal control group, ELOVL6 had the lowest expression level in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 4 weeks(P<0.01), and it showed better syndrome differentiation effectiveness of rats modeled for 4 weeks(AUC=0.850, P=0.006) than at other modeling time points(8, 12, 16, and 21 weeks, AUC of 0.689, 0.766, 0.588, and 0.662, respectively). Compared with that in the non-SONFH group, the expression levels of ANK1, GYPA, and RHAG were the lowest in the peripheral blood of SONFH patients with the vessel obstruction syndrome(P<0.05). The expression levels of the three genes were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 12 weeks(P<0.05, P<0.01), and their syndrome differentiation effectiveness in the rats modeled for 12 weeks(GYPA: AUC=0.861, P=0.012; ANK1: AUC=0.855, P=0.006; RHAG: AUC=0.854, P=0.009) was superior to that for 4, 8, 16, and 21 weeks(GYPA: AUC=0.646, 0.573, 0.691, and 0.617, respectively; ANK: AUC1=0.630, 0.658, 0.657, and 0.585, respectively; RHAG: AUC=0.592, 0.511, 0.515, and 0.536, respectively). Compared with the non-SONFH group, both SLC2A1 and STOM had the lowest expression levels in the peripheral blood of patients with the syndrome of liver and kidney deficiency(P<0.05). Compared with the normal control group, their expression levels were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 21 weeks(P<0.05, except STOM in the peripheral blood of rats). Moreover, the syndrome differentiation effectiveness of SLC2A1 in the rats modeled for 21 weeks(AUC=0.806, P=0.009) was superior to that for 4, 8, 12, and 16 weeks(AUC=0.520, 0.580, 0.741, 0.774, respectively), and STOM was meaningless in syndrome differentiation. In summary, the candidate marker gene for phlegm in SONFH is ELOVL6; the candidate marker genes for stasis are GYPA, RHAG, and ANK1; the candidate marker gene for deficiency is SLC2A1. The results help to reveal the biological connotations of phlegm, stasis, and deficiency in SONFH at the genetic level.
Subject(s)
Animal Experimentation , Osteonecrosis , Vascular Diseases , Humans , Rats , Animals , Transcriptome , Femur Head , Syndrome , Steroids/adverse effectsABSTRACT
Objective: To assess the effectiveness of myofascial release (MFR) techniques on the intensity of headache pain and associated disability in patients with tension-type headache (TTH), cervicogenic headache (CGH), or migraine. Design: A systematic review and meta-analysis. Methods: Eight databases were searched on September 15, 2023, including PubMed, Scopus, Web of Science, CINAHL, Cochrane Library, Embase, CNKI, and Wanfang Database. The risk of bias was evaluated utilizing the Cochrane Risk of Bias 2 (RoB 2) tool. Results: Pooled results showed that MFR intervention significantly reduces pain intensity [SMD = -2.01, 95% CI (-2.98, -1.03), I2 = 90%, P < 0.001] and improves disability [SMD = -1.3, 95% CI (-1.82, -0.79), I2 = 74%, P < 0.001]. Subgroup analysis based on the type of headache revealed significant reductions in pain intensity for CGH [SMD = -2.01, 95% CI (-2.73, -1.29), I2 = 63%, P < 0.001], TTH [SMD = -0.86, 95% CI (-1.52, -0.20), I2 = 50%, P=0.01] and migraine [SMD = -6.52, 95% CI (-8.15, -4.89), P < 0.001] and in disability for CGH [SMD = -1.45, 95% CI (-2.07, -0.83), I2 = 0%, P < 0.001]; TTH [SMD = -0.98, 95% CI (-1.32, -0.65), I2 = 0%, P < 0.001] but not migraine [SMD = -2.44, 95% CI (-6.04, 1.16), I2 = 97%, P=0.18]. Conclusion: The meta-analysis results indicate that MFR intervention can significantly alleviate pain and disability in TTH and CGH. For migraine, however, the results were inconsistent, and there was only moderate quality evidence of disability improvement for TTH and CGH. In contrast, the quality of other evidence was low or very low.
Subject(s)
Migraine Disorders , Post-Traumatic Headache , Tension-Type Headache , Humans , Post-Traumatic Headache/therapy , Myofascial Release Therapy , Migraine Disorders/therapy , Headache , Tension-Type Headache/therapy , PainABSTRACT
BACKGROUND: Fried foods are favored for their unique crispiness, golden color and flavor, but they also face great challenge because of their high oil content, high calories and the existence of compounds such as acrylamide and polycyclic aromatic hydrocarbons. Long-term consumption of fried foods may adversely affect health. Therefore, it is necessary to explore fried foods with lower oil contents and a high quality to meet the demand. RESULTS: A method of enzyme treatment was explored to investigate the effects of maltogenic amylase (MA), transglutaminase (TG) and bromelain (BRO) on the physicochemical properties of the batter and the quality of fried spring roll wrapper (FSRW). The results showed that the MA-, TG- or BRO-treated batters had a significant shear-thinning behavior, especially with an increase in viscosity upon increasing TG contents. FSRW enhanced its fracturability from 419.19 g (Control) to 616.50 g (MA-6 U g-1), 623.49 g (TG-0.75 U g-1) and 644.96 g (BRO-10 U g-1). Meanwhile, in comparison with BRO and MA, TG-0.5 U g-1 endowed batter with the highest density and thermal stability. MA-15 U g-1 and TG-0.5 U g-1 displayed FSRW with uniform and dense pores, and significantly reduced its oil content by 18.05% and 25.02%, respectively. Moreover, compared to MA and TG, BRO-50 U g-1 improved the flavor of FSRW. CONCLUSION: MA, TG or BRO played a key role in affecting the physicochemical properties of the batter and the quality of FSRW. TG-0.5 U g-1 remarkly reduced the oil content of FSRW with a great potential in practical application. © 2024 Society of Chemical Industry.
Subject(s)
Bromelains , Cooking , Transglutaminases , Transglutaminases/chemistry , Bromelains/chemistry , Viscosity , Fruit/chemistry , Glycoside Hydrolases/chemistry , Glycoside Hydrolases/metabolism , Flour/analysis , Taste , Food Handling/methodsABSTRACT
BACKGROUND: Diabetes is a metabolic disorder characterized by chronic hyperglycaemia. Chronic metabolic abnormalities and long-term hyperglycaemia may result in a wide range of acute and chronic consequences. Previous studies have demonstrated that artesunate(ART) has antidiabetic, anti-inflammatory, antiatherosclerotic, and other beneficial effects, but the specific regulatory mechanism is not completely clear. AIM: This study investigated the effects of ART on metabolic disorders in type 2 diabetes mellitus (T2DM) model db/db mice and explored the underlying mechanisms involved. METHODS: C57BL/KsJ-db/db mice were used to identify the targets and molecular mechanism of ART. Metabolomic methods were used to evaluate the efficacy of ART in improving T2DM-related metabolic disorders. Network pharmacology and transcriptomic sequencing were used to analyse the targets and pathways of ART in T2DM. Finally, molecular biology experiments were performed to verify the key targets and pathways selected by network pharmacology and transcriptomic analyses. RESULTS: After a 7-week ART intervention (160 mg/kg), the glucose and lipid metabolism levels of the db/db mice improved. Additionally, the oxidative stress indices, namely, the MDA and SOD levels, significantly improved (p<0.01). Linoleic acid and glycerophospholipid metabolism, amino acid metabolism, bile acid synthesis, and purine metabolism disorders in db/db mice were partially corrected after ART treatment. Network pharmacology analysis identified important targets of ART for the treatment of metabolic disorders in T2DM . These targets are involved in key signalling pathways, including the highest scores observed for the PI3K/Akt signalling pathway. Transcriptomic analysis revealed that ART could activate the MAPK signalling pathway and two key gene targets, HGK and GADD45. Immunoblotting revealed that ART increases p-PI3K, p-AKT, Glut2, and IRS1 protein expression and suppresses the phosphorylation of p38, ERK1/2, and JNK, returning HGK and GADD45 to their preartesunate levels. CONCLUSION: Treatment of db/db mice with 160 mg/kg ART for 7 weeks significantly reduced fasting blood glucose and lipid levels. It also improved metabolic imbalances in amino acids, lipids, purines, and bile acids, thereby improving metabolic disorders. These effects are achieved by activating the PI3K/AKT pathway and inhibiting the MAPK pathway, thus demonstrating the efficacy of the drug.
Subject(s)
Diabetes Mellitus, Type 2 , Hyperglycemia , Mice , Animals , Glucose/metabolism , MAP Kinase Signaling System , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Artesunate/pharmacology , Artesunate/therapeutic use , Diabetes Mellitus, Type 2/metabolism , Lipid Metabolism , Liver , Mice, Inbred C57BL , Hyperglycemia/metabolism , Mice, Inbred Strains , MetabolomeABSTRACT
Introduction: The effectiveness and safety of the Chinese herbal medicine (CHM) Xiao Yao San (XYS) used for treating anxiety disorders are still unknown. Thus, we conducted this systematic review with meta-analysis and trial sequential analysis (TSA) to determine its safety and efficacy. Methods: We searched 12 databases for relevant studies from the inception of each database till 10 August 2023. We selected randomized controlled trials to compare the efficacy and safety of XYS (including XYS only and XYS + anxiolytics) to those of anxiolytics in patients with anxiety. Results: We found 14 trials with 1,256 patients in total that met the requirements for inclusion. We assessed the majority of studies (8 out of 14) as being at high risk of bias; 6 were assessed as having a moderate risk of bias. Three trials compared oral XYS to anxiolytic medication, and 11 trials compared oral XYS plus anxiolytics to anxiolytic treatment alone. The pooled results showed that the efficacy of treatment in the XYS + anxiolytics groups was significantly higher than that of the anxiolytics alone group (RR = 1.19; 95% CI: [1.13, 1.26]; p < 0.00001; I2 = 0) and the adverse event rates in the XYS + anxiolytics groups were significantly lower than those in the anxiolytics alone group (RR = 0.44; 95% CI: [0.28, 0.82]; p = 0.001 < 0.05; I2 = 13). The efficacy of treatment in the XYS alone groups was also significantly higher than that of the anxiolytics alone groups (RR = 5.41; 95% CI: [2.23, 13.11]; p < 0.0001; I2 = 0). However, there was no statistical difference between the adverse events of the XYS alone group and the anxiolytics alone group, although the incidence of adverse events in the XYS alone group was lower than that in the anxiolytics alone group. The results of the TSA confirmed the above findings. Conclusion: The use of XYS combined with anxiolytics for treating anxiety was found to be safe and effective. However, although XYS alone is effective in the treatment of anxiety disorder, more large-scale research is needed to investigate adverse events. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=350358, identifier CRD42022350358.
ABSTRACT
Objective: The main treatment for essential hypertension at this stage is pharmacotherapy. Long-term pharmacotherapy is costly with some side effects. Tai Chi, a bright star in traditional Chinese arts, relaxes both mind and body and has been shown to relax blood vessels and lower blood pressure. This study aimed to systematically review the therapeutic effectiveness of the Tai Chi exercise cycle on blood pressure and cardiovascular risk factors of patients with essential hypertension. Methods: Searching CNKI, VIP, CBM, PubMed, EBSCO, Embase, Cochrane Library, and Web of Science to collect randomized controlled trials about Tai Chi exercise in the treatment of patients with essential hypertension according to the inclusion and exclusion criteria. The search time ranged from the date of database construction to December 2022. The Cochrane risk-of-bias tool was used to evaluate the included trials. The meta-analysis was performed with RevMan5.3 and Stata12.0 software. Results: According to the meta-analysis, compared with the controls, Tai Chi exercise with a cycle of more than 12 weeks may be better for the reduction of systolic blood pressure (SBP) [MD = -11.72, 95% CI (-15.52, -7.91)] and diastolic blood pressure (DBP) [MD = -4.68, 95% CI (-7.23, -2.12)], as well as increasing the content of nitric oxide (NO) [MD = 0.99, 95% CI (0.69, 1.28)]. The blood lipid metabolism ability may also be improved after more than 12 weeks of Tai Chi exercise, total cholesterol (TC) [SMD = -0.68, 95% CI (-0.89, -0.46), triglyceride (TG) [SMD = -0.84, 95% CI (-1.25, -0.43)], low-density lipoprotein cholesterol (LDL-C) [SMD = -1.58, 95% CI (-2.29, -0.86)]. However, the improvement of high-density lipoprotein cholesterol (HDL-C) [SMD = 0.54, 95% CI (0.28, 0.79)] was better with a less than 12 weeks exercise cycle. A subgroup analysis for exercise frequency and time showed that the exercise frequency should preferably be more than or equal to 5 times per week for patients with hypertension, and for patients with hypertension plus hyperlipidemia, the exercise frequency less than 5 times per week with exercise time less than 60â min each day may be more beneficial. Conclusion: The meta-analysis indicated that a more than 12 weeks Tai Chi exercise cycle with less than 60â min each time and more than 5 times per week may be more beneficial in blood pressure reduction, NO level increasing and blood lipid metabolism improving in the comparison with the other exercise cycles. For patients with hypertension plus hyperlipidemia, exercise frequency of less than 5 times per week may be better. Systematic Review Registration: [http://www.crd.york.ac.uk/prospero], identifier [CRD42022352035].
ABSTRACT
AIMS: Central melanocortin 4 receptor (MC4R) has been reported to induce anhedonia via eliciting dysfunction of excitatory synapses. It is evident that metabolic signals are closely related to chronic stress-induced depression. Here, we investigated that a neural circuit is involved in melanocortin signaling contributing to susceptibility to stress. METHODS: Chronic social defeat stress (CSDS) was used to develop depressive-like behavior. Electrophysiologic and chemogenetic approaches were performed to evaluate the role of paraventricular thalamus (PVT) glutamatergic to nucleus accumbens shell (NAcsh) circuit in stress susceptibility. Pharmacological and genetic manipulations were applied to investigate the molecular mechanisms of melanocortin signaling in the circuit. RESULTS: CSDS increases the excitatory neurotransmission in NAcsh through MC4R signaling. The enhanced excitatory synaptic input in NAcsh is projected from PVT glutamatergic neurons. Moreover, chemogenetic manipulation of PVTGlu -NAcsh projection mediates the susceptibility to stress, which is dependent on MC4R signaling. Overall, these results reveal that the strengthened excitatory neurotransmission in NAcsh originates from PVT glutamatergic neurons, facilitating the susceptibility to stress through melanocortin signaling. CONCLUSIONS: Our results make a strong case for harnessing a thalamic circuit to reorganize excitatory synaptic transmission in relieving stress susceptibility and provide insights gained on metabolic underpinnings of protection against stress-induced depressive-like behavior.
Subject(s)
Nucleus Accumbens , Receptor, Melanocortin, Type 4 , Nucleus Accumbens/metabolism , Receptor, Melanocortin, Type 4/genetics , Receptor, Melanocortin, Type 4/metabolism , Thalamus , Neurons/metabolism , Synaptic TransmissionABSTRACT
Background/objectives: Aerobic and resistance training are common complementary therapies to improve motor symptoms in people with Parkinson's disease (PD), and there is still a lack of advice on which intensity and period of aerobic or resistance training is more appropriate for people with PD. Therefore, a network meta-analysis was conducted to assess the comparative efficacy of aerobic and resistance training of different intensities and cycles on motor symptoms in patients with Parkinson's disease. Methods: Based on several biomedical databases, a search strategy system was conducted to retrieve randomized controlled trials (RCTs) without language restrictions. A network meta-analysis with a frequentist approach was conducted to estimate the efficacy and probability rankings of aerobic and resistance training on Parkinson's patients. What's more, a range of analyses and assessments, such as routine meta-analyses and risk of bias, were performed as well. Results: Twenty trials with 719 patients evaluating 18 different therapies were identified. Through the Unified Parkinson's Disease Motor Rating Scale, (UPDRS III); 6-minute walk test, (6MWT); 10-meter walk test, (TWM); and time up and go (TUG) and Quality of Life Scale-39 (PDQ-39), to explore the effects of different intensity resistance and aerobic exercise on PD. As a result, short period high intensity resistance movement (standard mean difference (SMD) = -0.95, 95% confidence interval (CI) -1.68 to -0.22) had significantly decreased the Unified Parkinson's Disease Motor Rating Scale (UPDRS III). Short period high intensity resistance exercise showed similar superiority in other indices; also, aerobic and resistance training of different cycle intensities produced some efficacy in PD patients, both in direct and indirect comparisons. Conclusion: For patients with moderate to mild Parkinson's symptoms, short periods high intensity resistance training may provide complementary therapy for PD, and aerobic or resistance training of varying intensity and periodicity may be recommended as exercise prescription for PD patients. However, more large scale and high quality clinical trials are needed to confirm the effectiveness of this exercise therapy in the future. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022324824.
ABSTRACT
Objective: This study aimed to examine the urban-rural disparities and associated factors of health care utilization among cancer patients in China. Methods: This study used the data collected from a cross-sectional survey conducted in China. A total of 1,570 cancer survivors from three urban districts and five rural counties were selected by using a multistage stratified random sampling method. We measured health care utilization with the way of cancer diagnosis, the number of hospitals visited, and receiving alternative therapies. Chi-square test was used to examine the differences between urban and rural cancer patients. Binary logistic regression analysis was performed to explore the determinants of health care utilization. Results: Among 1,570 participants, 84.1% were diagnosed with cancer after developing symptoms, 55.6% had visited two and above hospitals, and 5.7% had received alternative therapies. Compared with urban cancer patients, rural ones were more likely to be diagnosed with cancer after developing symptoms (χ2 = 40.04, p < 0.001), while they were less likely to visit more than one hospital (χ2 = 27.14, p < 0.001). Residence area (urban/rural), health insurance type, household income, age at diagnosis, tumor site, stage of tumor, and survival years were significantly associated with health care utilization of cancer patients (p < 0.01). Conclusions: Health care utilization was suboptimal among cancers patients in China. Rural cancer patients had less health care utilization including screenings and treatments than urban ones. Policymakers should implement specific strategies to ensure equitable utilization of cancer care. More attention should be paid to the disadvantaged groups and rural cancer patients. Prioritizing health resources allocation is needed to prevent, screen, and treat cancers in rural areas.
Subject(s)
Neoplasms , Rural Population , China/epidemiology , Cross-Sectional Studies , Humans , Neoplasms/therapy , Patient Acceptance of Health CareABSTRACT
Erhai Lake is the second largest freshwater lake in Yunnan Province but suffers from the deterioration of water quality and agricultural non-point source pollution (ANPSP). However, little is known about the influence of ANPSP on the water quality of Erhai Lake. The export coefficient model (ECM) was used to obtain the total nitrogen (TN) and total phosphorus (TP) loads from ANPSP in Erhai Lake Basin (ELB). The trophic status of Erhai Lake as influenced by such sources of nutrient input was also been assessed. Results indicated that the TN and TP loads in ELB increased from 1985 to 2005 due to sustainable agricultural development; thereafter, the TN and TP loads decreased from 2005 to 2020, indicating that agricultural pollution prevention improved in ELB. The northern part of ELB had higher pollution intensity than the southern part and the central part, indicating that the ecosystem in the northern part of ELB appeared to be vulnerable. Driving force analysis showed that cattle breeding was the main reason for the exported TN loads in most watersheds, and intensive agricultural planting was the major contributor to TP loads. The mean annual Chl-a concentration had a strong correlation with the TN and TP loads exported from north of ELB, and this finding suggested that ANPSP could lead to eutrophication. The results of this study demonstrate the impacts of agricultural activities on water quality at the watershed scale and provide a scientific foundation for lake management decision-making.
Subject(s)
Agriculture , Chlorophyll A , Lakes , Water Pollutants, Chemical , Animals , Cattle , China , Chlorophyll A/analysis , Ecosystem , Lakes/chemistry , Nitrogen/analysis , Phosphorus/analysis , Water Pollutants, Chemical/analysis , Water QualityABSTRACT
RATIONALE: Currently, placenta accreta treatment mainly includes nonconservative surgical and conservative treatments such as Traditional Chinese medicine (TCM). This report describes the case of a 37-year-old woman who suffered incomplete placenta accreta after vaginal delivery and was cured by TCM. TCM treatment of placenta accreta has its own unique advantages, including low toxicity and few side effects, unaffected breastfeeding, and retention of the uterus, which can ensure the expulsion of residual placenta and be beneficial to patients' physical and mental health. PATIENT CONCERNS: Symptoms included a small amount of vaginal bleeding and occasional lesser abdominal pain. The patient showed lesser abdominal tenderness, a red tongue moss with petechial hemorrhage, and a hesitant pulse. The reproductive history was G3P2L2A1. In addition, the patient was afraid of having her uterus removed due to incomplete placental separation. DIAGNOSES: The case was diagnosed as placental accreta. Ultrasound is the preferred method of diagnosis, and biomarkers, such as beta hCG, assist in screening for placental accreta. Doppler ultrasonography showed that in the bottom of the right uterine cavity, there was an uneven echo group of 7.6â×â4.6âcm, which was not clearly demarcated from the posterior wall; the muscle layer became thinner, with a thinnest part of 0.19âcm, and abundant blood flow signals were observed (Fig. 1JOURNAL/medi/04.03/00005792-202102190-00086/figure1/v/2021-02-16T234818Z/r/image-tiff). The beta hCG was 580.92âmIu/ml. INTERVENTIONS: The patient initially underwent curettage therapy 9âdays after delivery, but it failed due to excessive intraoperative bleeding. The patient then turned to TCM treatment. The doctor prescribed a multi-herbal formula. OUTCOMES: After 4âmonths, the residual placenta was expelled, and the patient's symptoms disappeared completely. No adverse and unexpected events occurred during treatment. During 3âmonths of follow-up, the patient had no abdominal pain, abnormal vaginal bleeding, or other complications. LESSONS: This study shows that TCM is safe and effective for treating placenta accreta, and it is worth recommending TCM as a conservative treatment along with other treatments. In practice, however, we find that the earlier TCM treatment is applied, the better the effect; therefore, early intervention with TCM is particularly important.
Subject(s)
Medicine, Chinese Traditional/methods , Placenta Accreta/diagnostic imaging , Placenta Accreta/therapy , Ultrasonography, Doppler/methods , Adult , Aftercare , Chorionic Gonadotropin, beta Subunit, Human/metabolism , Conservative Treatment/methods , Female , Humans , Placenta Accreta/metabolism , Pregnancy , Treatment Outcome , Uterine Hemorrhage/etiologyABSTRACT
OBJECTIVE: To evaluate the efficacy of spirit-regulating electroacupuncture (EA), cognitive behavioral therapy (CBT), and combined EA/CBT to treat insomnia. METHODS: In this prospective clinical study, patients were randomly assigned to receive EA, CBT, or EA/CBT. Outcomes were assessed using PSQI, ISI, ESS, DBAS-16, HAM-A, and HAM-D at two- and four-week follow-up. RESULTS: Overall, the PSQI and ISI scores decreased after treatment in all three groups. At two-week follow-up, the EA/CBT group obtained lower PSQI and ISI scores than the EA group. The daytime functional factor score in the EA group was lower than that of the CBT group after the second week of treatment, and the EA/CBT PSQI score was lower than that of the CBT group on the second week of follow-up. In comparison with baseline, the EA group had a decreased ESS score after the second and fourth weeks of treatment, while the ESS score increased in the CBT group after the fourth week of treatment. ESS scores were unchanged following treatment in the EA/CBT group. After the second and fourth weeks of treatment, the ESS scores from the CBT group were higher than the EA group. The DBAS-16 decreased in the CBT and EA/CTB groups, while the EA group had a higher DBAS-16 score. In all three groups, HAM-A and HAM-D scores decreased after treatment; the EA/CBT HAM-A and HAM-D scores were lower than the other two groups. CONCLUSION: 1. Spirit-regulating EA therapy is effective. In terms of improving sleep quality and mood, EA has the same effect as CBT and can improve daytime function earlier. 2. The curative effect of the EA/CBT group lasts longer than that of the EA group, and EA/CBT is better at improving daytime function compared to CBT alone and better at improving mood compared to CBT or EA alone.
ABSTRACT
Misalignment between natural light rhythm and modern life activities induces disruption of the circadian rhythm. It is mainly evident that light at night (LAN) interferes with the human endocrine system and contributes to the increasing rates of obesity and lipid metabolic disease. Maintaining hepatointestinal circadian homeostasis is vital for improving lipid homeostasis. Melatonin is a chronobiotic substance that plays a main role in stabilizing bodily rhythm and has shown beneficial effects in protecting against obesity. Based on the dual effect of circadian rhythm regulation and antiobesity, we tested the effect of melatonin in mice under constant light exposure. Exposure to 24-h constant light (LL) increased weight and insulin resistance compared with those of the control group (12-h light-12-h dark cycle, LD), and simultaneous supplementation in the melatonin group (LLM) ameliorated this phenotype. Constant light exposure disturbed the expression pattern of a series of transcripts, including lipid metabolism, circadian regulation and nuclear receptors in the liver. Melatonin also showed beneficial effects in improving lipid metabolism and circadian rhythm homeostasis. Furthermore, the LL group had increased absorption and digestion of lipids in the intestine as evidenced by the elevated influx of lipids in the duodenum and decrease in the efflux of lipids in the jejunum. More interestingly, melatonin ameliorated the gut microbiota dysbiosis and improved lipid efflux from the intestine. Thus, these findings offer a novel clue regarding the obesity-promoting effect attributed to LAN and suggest a possibility for obesity therapy by melatonin in which melatonin could ameliorate rhythm disorder and intestinal dysbiosis.
Subject(s)
Circadian Clocks/drug effects , Circadian Rhythm/drug effects , Homeostasis/drug effects , Light , Lipid Metabolism/drug effects , Melatonin/metabolism , Melatonin/pharmacology , Animals , Cell Line , Dysbiosis/drug therapy , Gastrointestinal Microbiome/drug effects , Hepatocytes/drug effects , Hepatocytes/metabolism , Humans , Insulin Resistance/radiation effects , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Liver/drug effects , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Weight Gain/drug effects , Weight Gain/radiation effectsABSTRACT
BACKGROUND: Primary insomnia (PI) is one of the most common complaints among the general population. Both non-pharmacological and pharmacological therapies have proven effective in treating primary insomnia. However, the underlying mechanism of treatment remains unclear, and no studies have compared the underlying mechanisms of different treatments. METHODS: In this study, we investigated gray matter volume (GMV) and resting-state functional connectivity (rsFC) changes following both pharmacological and non-pharmacological treatments in patients with PI. A total of 67 PI patients were randomized into benzodiazepine treatment, cupping treatment, or a wait-list control group for 4â¯weeks. The Pittsburgh Sleep Quality Index (PSQI), gray matter volume (GMV), and resting-state functional connectivity (rsFC) of the hippocampus were measured at the beginning and end of the experiment. RESULTS: We found 1) significantly decreased PSQI scores in the cupping and benzodiazepine treatment groups compared to the control group with no significant differences between the two treatment groups; 2) significant GMV increases in the cupping group compared to the control group at the right hippocampus after 4â¯weeks of treatment; 3) significantly increased rsFC between the right hippocampus and left rostral anterior cingulate cortex/medial prefrontal cortex (rACC/mPFC) in the two treatment groups, which was significantly associated with PSQI score decreases. DISCUSSION: Our findings suggest that benzodiazepine and cupping may share a common mechanism to relieve the symptoms of patients with PI.
Subject(s)
Benzodiazepines/therapeutic use , Cupping Therapy/methods , Gray Matter/diagnostic imaging , Nerve Net/diagnostic imaging , Sleep Initiation and Maintenance Disorders/diagnostic imaging , Waiting Lists , Adult , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging/methods , Male , Middle Aged , Sleep Initiation and Maintenance Disorders/psychology , Sleep Initiation and Maintenance Disorders/therapyABSTRACT
Ionic liquid-based salt-induced liquid-liquid extraction was developed for the first time and applied to the extraction of four active constituents, including polydatin, resveratrol, emodin, and physcion in Polygonum cuspidatum (P. cuspidatum). In this study, ionic liquid was used as extraction solvent. The dried P. cuspidatum samples purchased from the pharmacy were triturated and passed through a 120-mesh sieve. The obtained sample powders were dried to constant weight at 55 â, and then mixed with extraction solvent. The extraction was carried out with the aid of ultrasound. Three phases, including ionic liquid-rich, salt-rich and solid sample phases were formed in the presence of salt. The target analytes were enriched in ionic liquid phase and then determined by high performance liquid chromatography. The experimental parameters, such as type and volume of ionic liquid, type and amount of salt, pH value of extraction medium, ultrasound power, ultrasound time and centrifugal condition, were optimized. The calibration curves showed good linear relationship (r > 0.9994). The limits of detection and quantification were in the range of 2.8-29.5 and 9.4-98.3 ng mL-1, respectively. The spiked recoveries were between 92.16% and 105.41%. Compared with hot reflux extraction and ultrasound-assisted extraction, the proposed method requires less extraction solvent and time. The present method can be applied to the determination of polyphenols and anthraquinones in P. cuspidatum.
Subject(s)
Anthraquinones/analysis , Drugs, Chinese Herbal/analysis , Fallopia japonica/chemistry , Liquid-Liquid Extraction/methods , Polyphenols/analysis , Anthraquinones/chemistry , Chromatography, High Pressure Liquid/instrumentation , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/chemistry , Ionic Liquids/chemistry , Liquid-Liquid Extraction/instrumentation , Plant Roots/chemistry , Polyphenols/chemistry , Time Factors , Ultrasonic WavesABSTRACT
BACKGROUND: DBZ (Danshensu Bingpian Zhi), a synthetic derivative of a natural compound found in traditional Chinese medicine, has been reported to suppress lipopolysaccharide-induced macrophage activation and lipid accumulation in vitro. The aim of this study was to assess whether DBZ could attenuate atherosclerosis at early and advanced stages. METHODS AND RESULTS: The effects of DBZ on the development of atherosclerosis were studied using apolipoprotein E-deficient (apoE-/-) mice. For early treatment, 5-week-old apoE-/- mice were fed a Western diet and treated daily by oral gavage with or without DBZ or atorvastatin for 10 weeks. For advanced treatment, 5-week-old apoE-/- mice were fed a Western diet for 10 weeks to induce atherosclerosis, and then they were randomly divided into 4 groups and subjected to the treatment of vehicle, 20 mg/kg per day DBZ, 40 mg/kg per day DBZ, or 10 mg/kg per day atorvastatin for the subsequent 10 weeks. We showed that early treatment of apoE-/- mice with DBZ markedly reduced atherosclerotic lesion formation by inhibiting inflammation and decreasing macrophage infiltration into the vessel wall. Treatment with DBZ also attenuated the progression of preestablished diet-induced atherosclerotic plaques in apoE-/- mice. In addition, we showed that DBZ may affect LXR (liver X receptor) function and that treatment of macrophages with DBZ suppressed lipopolysaccharide-stimulated cell migration and oxidized low-density lipoprotein-induced foam cell formation. CONCLUSIONS: DBZ potentially has antiatherosclerotic effects that involve the inhibition of inflammation, macrophage migration, leukocyte adhesion, and foam cell formation. These results suggest that DBZ may be used as a therapeutic agent for the prevention and treatment of atherosclerosis.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Aorta/drug effects , Aortic Diseases/prevention & control , Atherosclerosis/prevention & control , Camphanes/pharmacology , Drugs, Chinese Herbal/pharmacology , Phenylpropionates/pharmacology , Animals , Aorta/metabolism , Aorta/pathology , Aortic Diseases/genetics , Aortic Diseases/metabolism , Aortic Diseases/pathology , Atherosclerosis/genetics , Atherosclerosis/metabolism , Atherosclerosis/pathology , Atorvastatin/pharmacology , Cell Adhesion/drug effects , Cell Movement/drug effects , Cholesterol/metabolism , Diet, Western , Disease Models, Animal , Foam Cells/drug effects , Foam Cells/metabolism , Foam Cells/pathology , HEK293 Cells , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Leukocytes/drug effects , Leukocytes/metabolism , Leukocytes/pathology , Lipopolysaccharides/pharmacology , Lipoproteins, LDL/pharmacology , Liver X Receptors/genetics , Liver X Receptors/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout, ApoE , Plaque, Atherosclerotic , RAW 264.7 Cells , THP-1 CellsABSTRACT
BACKGROUND: The nuclear receptor PPARγ is an effective pharmacological target for some types of metabolic syndrome, including obesity, diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. However, the current PPARγ-targeting thiazolidinedione drugs have undesirable side effects. Danshensu Bingpian Zhi (DBZ), also known as tanshinol borneol ester derived from Salvia miltiorrhiza, is a synthetic derivative of natural compounds used in traditional Chinese medicine for its anti-inflammatory activity. METHODS: In vitro, investigations of DBZ using a luciferase reporter assay and molecular docking identified this compound as a novel promising PPARγ agonist. Ten-week-old C57BL/6J mice were fed either a normal chow diet (NCD) or a high-fat diet (HFD). The HFD-fed mice were gavaged daily with either vehicle or DBZ (50mg/kg or 100mg/kg) for 10weeks. The gut microbiota composition was assessed by analyzing the 16S rRNA gene V3+V4 regions via pyrosequencing. RESULTS: DBZ is an efficient natural PPARγ agonist that shows lower PPARγ-responsive luciferase reporter activity than thiazolidinediones, has excellent effects on the metabolic phenotype and exhibits no unwanted adverse effects in a HFD-induced obese mouse model. DBZ protects against HFD-induced body weight gain, insulin resistance, hepatic steatosis and inflammation in mice. DBZ not only stimulates brown adipose tissue (BAT) browning and maintains intestinal barrier integrity but also reverses HFD-induced intestinal microbiota dysbiosis. CONCLUSIONS: DBZ is a putative PPARγ agonist that prevents HFD-induced obesity-related metabolic syndrome and reverse gut dysbiosis. GENERAL SIGNIFICANCE: DBZ may be used as a beneficial probiotic agent to improve HFD-induced obesity-related metabolic syndrome in obese individuals.
Subject(s)
Camphanes/administration & dosage , Dysbiosis/drug therapy , Insulin Resistance , Obesity/drug therapy , PPAR gamma/genetics , Phenylpropionates/administration & dosage , Camphanes/chemistry , Diet, High-Fat/adverse effects , Dysbiosis/genetics , Dysbiosis/pathology , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/genetics , Humans , Medicine, Chinese Traditional , Molecular Docking Simulation , Obesity/etiology , Obesity/physiopathology , PPAR gamma/agonists , PPAR gamma/chemistry , Phenylpropionates/chemistry , RNA, Ribosomal, 16S/genetics , Salvia miltiorrhiza/chemistryABSTRACT
This study was designed to explore the effects and mechanism of isoliensinine (isolie) from embryos of Nelumbo nucifera on type 2 diabetes and dyslipidemia in vivo and in vitro. The in vitro study showed that isolie increased the GLUT4 translocation by 2.5-fold in L6 cells. Furthermore, after 4 weeks of treatment, the in vivo biochemical study indexes revealed that isolie had a positive effect on decreasing serum insulin level (42.2 ± 5.10 vs 55.7 ± 6.33 mU/L, P < 0.05) and reducing fast blood glucose (9.4 ± 1.5 vs 18.7 ± 2.3 mmol/L, P < 0.001) and body weight (37.8 ± 2.9 vs 46.9 ± 5.4 g, P < 0.05) compared with the KK-Ay model mice. Isolie treatment led to significant increases in GLUT4 proteins (â¼2.7-fold in skeletal muscle and â¼2.4-fold in WAT) and phosphorylated AMP-activated protein kinase (â¼1.4-fold in skeletal muscle, â¼3.1-fold in WAT, and â¼2.3-fold in liver). However, isolie caused a significant decrease in lipogenesis protein expressions of PPARγ and SREBP-1c, and decreased the activity of ACC by increasing the phospho-ACC level. Our findings showed that isolie has the potential to alleviate type 2 diabetes associated with hyperlipidemia in KK-Ay mice. Regulation of GLUT4, SREBP-1c, PPARγ, AMPK phosphorylation, and ACC phosphorylation is implicated in the antidiabetic effects of isolie.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Hypoglycemic Agents/administration & dosage , Isoquinolines/administration & dosage , Nelumbo/chemistry , PPAR gamma/metabolism , Plant Extracts/administration & dosage , AMP-Activated Protein Kinases/genetics , Animals , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/enzymology , Diabetes Mellitus, Type 2/genetics , Female , Glucose Transporter Type 4/genetics , Glucose Transporter Type 4/metabolism , Humans , Insulin/metabolism , Liver/drug effects , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , PPAR gamma/genetics , Seeds/chemistryABSTRACT
Excess weight and obesity are severe public health threats worldwide. Recent evidence demonstrates that gut microbiota dysbiosis contributes to obesity and its comorbidities. The body weight-reducing and energy balancing effects of melatonin have been reported in several studies, but to date, no investigations toward examining whether the beneficial effects of melatonin are associated with gut microbiota have been carried out. In this study, we show that melatonin reduces body weight, liver steatosis, and low-grade inflammation as well as improving insulin resistance in high fat diet (HFD)-fed mice. High-throughput pyrosequencing of the 16S rRNA demonstrated that melatonin treatment significantly changed the composition of the gut microbiota in mice fed an HFD. The richness and diversity of gut microbiota were notably decreased by melatonin. HFD feeding altered 69 operational taxonomic units (OTUs) compare with a normal chow diet (NCD) group, and melatonin supplementation reversed 14 OTUs to the same configuration than those present in the NCD group, thereby impacting various functions, in particular through its ability to decrease the Firmicutes-to-Bacteroidetes ratio and increase the abundance of mucin-degrading bacteria Akkermansia, which is associated with healthy mucosa. Taken together, our results suggest that melatonin may be used as a probiotic agent to reverse HFD-induced gut microbiota dysbiosis and help us to gain a better understanding of the mechanisms governing the various melatonin beneficial effects.
Subject(s)
Gastrointestinal Microbiome/drug effects , Melatonin/pharmacology , Melatonin/therapeutic use , Obesity/metabolism , Obesity/prevention & control , Probiotics/therapeutic use , Animals , Bacteroidetes/drug effects , Bacteroidetes/isolation & purification , Blotting, Western , Central Nervous System Depressants/pharmacology , Central Nervous System Depressants/therapeutic use , Diet, High-Fat/adverse effects , Fatty Liver/metabolism , Fatty Liver/prevention & control , Firmicutes/drug effects , Firmicutes/isolation & purification , Glucose Intolerance/metabolism , Glucose Intolerance/prevention & control , Inflammation/metabolism , Inflammation/prevention & control , Insulin Resistance , Male , Mice , Mice, Inbred C57BL , Weight GainABSTRACT
Bioassay-guided phytochemical investigation of the EtOAc fraction (ST-EtOAc) from the roots of Sophora tonkinensis resulted in the isolation of a new compound 6aR,11aR-1-hydroxy-4-isoprenyl-maackiain (1), along with 12 known compounds (2-13). The structure of the new compound was established by 1D and 2D NMR, MS data and circular dichroism analysis. Polyprenylated flavonoids 6-9 and 11-13 increased GLUT-4 translocation by the range of 1.35-2.75 folds. Sophoranone (8) exerted the strongest activity with 2.75 folds GLUT-4 translocation enhancement at the concentration of 10µM. This is the first report of the GLUT-4 translocation activity of the plant Sophora tonkinensis.