ABSTRACT
To provide evidence for optimization of multi-kinase inhibitors (MKIs) use in the clinic, we use the public database to describe and evaluate electrolyte disorders (EDs) related to various MKIs treated for renal cell carcinoma. We analyzed spontaneous reports submitted to the Food and Drug Administration Adverse Events Reporting System (FAERS) in an observational and retrospective manner. Selecting electrolyte disorders' adverse events to multikinase inhibitors (axitinib, cabozantinib, lenvatinib, pazopanib, sunitinib, and sorafenib). We used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms to analyze suspected adverse reactions of electrolyte disorders induced by MKIs (which were treated for renal cell carcinoma) between January 2004 and December 2022. As of December 2022, 2772 MKIs (which were treated for renal cell carcinoma) ICSRs were related to electrolyte disorders AEs. In general, there were more AEs cases in males, except lenvatinib and 71.8% of the cases were submitted from North America. ICSRs in this study, the age group most frequently affected by electrolyte disorders AEs was individuals aged 45-64 years for axitinib, cabozantinib, pazopanib, and sunitinib, whereas electrolyte disorders AEs were more common in older patients (65-74 years) for sorafenib and lenvatinib. For all EDs documented in ICSRs (excluding missing data), the most common adverse outcome was hospitalization(1429/2674, 53.4%), and the most serious outcome was death/life-threat(281/2674, 10.5%). The prevalence of mortality was highest for sunitinib-related EDs (145/616, 23.5%), excluding missing data (n = 68), followed by cabozantinib-related EDs (20/237, 8.4%), excluding missing data (n = 1). The distribution of time-to-onset of Each drug-related ICSRs was not all the same, and the difference was statistically significant (P = 0.001). With the criteria of ROR, the six MKIs were all significantly associated with electrolyte disorders AEs, the strongest association was the association between cabozantinib and hypermagnesaemia. MKIs have been reported to have significant electrolyte disorders AEs. Patients and physicians need to recognize and monitor these potentially fatal adverse events.
Subject(s)
Anilides , Carcinoma, Renal Cell , Indazoles , Kidney Neoplasms , Phenylurea Compounds , Pyridines , Pyrimidines , Quinolines , Sulfonamides , Aged , Humans , Male , Axitinib/therapeutic use , Bayes Theorem , Carcinoma, Renal Cell/drug therapy , Electrolytes , Kidney Neoplasms/pathology , Pharmacovigilance , Retrospective Studies , Sorafenib/adverse effects , Sunitinib/adverse effects , United States , United States Food and Drug Administration , Female , Middle AgedABSTRACT
This study aims to investigate the effect of Buyang Huanwu Decoction on blood flow recovery and arteriogenesis after hindlimb ischemia in mice via the platelet-derived growth factor(PDGF) signaling pathway. Forty C57BL/6 mice were randomized into model(clean water, 10 mL·kg~(-1)·d~(-1)), beraprost sodium(positive control, 18 µg·kg~(-1)·d~(-1)), and low-, medium-, and high-dose(10, 20, and 40 g·kg~(-1)·d~(-1), respectively) Buyang Huanwu Decoction groups(n=8). The hindlimb ischemia model was established by femoral artery ligation. The mice were administrated with corresponding agents by gavage daily for 14 days after ligation. For laser Doppler perfusion imaging, the mice were anesthetized and measured under a Periscan PSI imager. The density of capillary and arterio-le in the ischemic gastrocnemius was measured using immunofluorescence staining of the frozen tissue sections. Western blot was employed to determine the expression of PDGF subunit B(PDGFB), phosphorylated mitogen extracellular kinase(p-MEK), MEK, phosphorylated extracellular signal-regulated kinase(p-ERK), and ERK. Real-time PCR was employed to determine the mRNA level of PDGFB. The Buyang Huanwu Decoction-containing serum was used to treat the vascular smooth muscle cells(VSMCs) in hypoxia at doses of 10% and 20%. The proliferation and migration of VSMCs was assessed in vitro. The results showed that compared with the model group, beraprost sodium and Buyang Huanwu Decoction enhanced the blood flow recovery, increased the capillary and arteriole density, and up-regulated the protein levels of PDGFB, p-MEK, p-ERK, and mRNA levels of PDGFB, with the medium-dose Buyang Huanwu Decoction demonstrating the most significant effect. The 10% Buyang Huanwu Decoction-containing serum enhanced the proliferation and migration of VSMCs. Our findings demonstrate that Buyang Huanwu Decoction up-regulates PDGFB transcription and activates PDGF signaling pathway to promote arteriogenesis and blood flow recovery in ischemic gastrocnemius.
Subject(s)
Drugs, Chinese Herbal , Rats , Mice , Animals , Rats, Sprague-Dawley , Proto-Oncogene Proteins c-sis , Mice, Inbred C57BL , Drugs, Chinese Herbal/therapeutic use , Signal Transduction , Ischemia/drug therapy , Hindlimb/metabolism , RNA, Messenger/metabolism , Mitogen-Activated Protein Kinase Kinases/metabolismABSTRACT
The concept of multi-target-directed ligands offers fresh perspectives for the creation of brand-new Alzheimer's disease medications. To explore their potential as multi-targeted anti-Alzheimer's drugs, eighteen new bakuchiol derivatives were designed, synthesized, and evaluated. The structures of the new compounds were elucidated by IR, NMR, and HRMS. Eighteen compounds were assayed for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in vitro using Ellman's method. It was shown that most of the compounds inhibited AChE and BuChE to varying degrees, but the inhibitory effect on AChE was relatively strong, with fourteen compounds showing inhibition of >50% at the concentration of 200 µM. Among them, compound 3g (IC50 = 32.07 ± 2.00 µM) and compound 3n (IC50 = 34.78 ± 0.34 µM) showed potent AChE inhibitory activities. Molecular docking studies and molecular dynamics simulation showed that compound 3g interacts with key amino acids at the catalytically active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase and binds stably to acetylcholinesterase. On the other hand, compounds 3n and 3q significantly reduced the pro-inflammatory cytokines TNF-α and IL-6 released from LPS-induced RAW 264.7 macrophages. Compound 3n possessed both anti-acetylcholinesterase activity and anti-inflammatory properties. Therefore, an in-depth study of compound 3n is expected to be a multi-targeted anti-AD drug.
Subject(s)
Alzheimer Disease , Butyrylcholinesterase , Phenols , Humans , Butyrylcholinesterase/chemistry , Butyrylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry , Molecular Docking Simulation , Molecular Structure , Structure-Activity Relationship , Drug DesignABSTRACT
BACKGROUND: Postpartum depression refers to a depressive episode or depressive symptoms up to 12 mo after delivery. Trait mindfulness has presented a protective factor for postpartum depressive symptoms and proved efficient in improving relationship satisfaction among couples. AIM: To investigate the correlations among mindfulness, marital quality, anxiety, and depression in a large city in western China during the post-corona virus infectious disease-2019 era and determine whether trait mindfulness mediates the relationship between marital quality and postpartum anxiety and depression among primiparas. METHODS: A cross-sectional study was conducted. The self-administered questionnaire was submitted online through smartphones. The levels of mindfulness, anxiety, depression, and marital quality were respectively investigated by the mindful attention awareness scale (MAAS), the self-rating anxiety scale (SAS), the self-rating depression scale (SDS), and the marriage perception scale (MPS) in these enrolled Han and Tujia primiparas. RESULTS: No statistical significance was observed in the prevalence of postpartum anxiety and depression, nor scores of MAAS and MPS-Total in different regions or ethnicities (P > 0.05). However, MPS-Marital interaction (P < 0.05), MPS-Family relationship (MPS-FR) (P < 0.01), and MPS-Marital conflict (MPS-MC) (P < 0.01) scores of urban primiparas were higher than those of rural primiparas. The MPS-MC score of Han primiparas was higher than that of Tujia primiparas (P < 0.05). Negative correlations were observed between MAAS and SAS (r = -0.457, P < 0.01), and MAAS and SDS (r = -0.439, P < 0.01). SAS has revealed a highly positive correlation with SDS (r = 0.720, P < 0.01) and a weak negative correlation with MPS (r = -0.200, P < 0.05). Besides, a weak negative correlation was observed between MAAS and MPS-MC (r = -0.184, P < 0.05), and a weak positive correlation was noticed between SAS and MPS-MC (r = -0.225, P < 0.01). Mediation analysis demonstrated a full mediation effect of mindfulness level on the relationship between MPS-FR and postpartum anxiety (P < 0.05, 95%CI: -0.384 to 0.033), MPS-MC and postpartum anxiety (P < 0.01, 95%CI: 0.027-0.193), MPS-FR and postpartum depression (P < 0.05, 95%CI: -0.365 to 0.031), and MPS-MC and postpartum depression (P < 0.01, 95%CI: 0.022-0.206). CONCLUSION: Mindfulness demonstrates negative correlations with marital conflict, postpartum anxiety and depression, and it may have cross-ethnic and trans-regional characteristics. Although the mindfulness levels have revealed no significant mediating effect between the total score of marital quality and postpartum depression in this study, it demonstrates a full mediation effect on the relationships between family relationships, marital conflict, and postpartum anxiety and depression.
ABSTRACT
Soluble iron and sulfate in acid mine drainage (AMD) can be greatly removed through the formation of minerals facilitated by seed crystals. However, the difference in the effects of jarosite and schwertmannite as endogenous seed crystals to induce AMD mineralization remains unclear. This paper intends to study the effect of Fe2+ oxidation and Fe3+ mineralization in the biosynthesis of minerals using different addition amounts and methods of jarosite or schwertmannite. The results showed that the addition amount and method of different seed crystals had no effect on the Fe2+ bio-oxidation but would change the Fe3+ mineralization efficiency. With the same amount of seed crystals added, jarosite exhibited a higher capacity to promote Fe3+ mineralization than schwertmannite. Adding seed crystals before the initiation of Fe2+ oxidation (0 h) could significantly promote Fe3+ mineralization efficiency. With the increase of seed crystals, jarosite could not only shorten the time required for mineral synthesis but also improve the final mineral yield, whereas schwertmannite could only shorten the time required for mineral synthesis. When Fe2+ was completely oxidized to Fe3+ (48 h), the supplementary of jarosite could still effectively improve Fe3+ mineralization efficiency, but the addition of schwertmannite no longer affected the final mineralization degree.
Subject(s)
Acidithiobacillus , Iron Compounds , Iron , Biomineralization , Iron Compounds/chemistry , Ferric Compounds/chemistry , Minerals , Oxidation-ReductionABSTRACT
BACKGROUND: The herbal pair of Salvia miltiorrhiza Bunge and Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep (DG) is commonly used in the treatment of type 2 diabetes (T2DM) in traditional Chinese medicine (TCM). The drug pair DG was designed by Dr. Zhu chenyu to improve the treatment of T2DM. AIM: This study combined with systematic pharmacology and urine metabonomics to explore the mechanism of DG in the treatment of T2DM. METHODS: The therapeutic effect of DG on T2DM was evaluated by fasting blood glucose (FBG) and biochemical indexes. Systematic pharmacology was used to screen the active components and targets that may be related to DG. Metabonomics was established to find urinary metabolites and pathways that may be induced by DG. Finally, integrate the results of these two parts for mutual verification. RESULTS: FBG and biochemical indexes showed that DG could reduce FBG and adjust the related biochemical indexes. Metabolomics analysis indicated that 39 metabolites were related to DG for T2DM treatment. In addition, systematic pharmacology showed compounds and potential targets which were associated with DG. Finally, 12 promising targets were selected as targets for T2DM therapy by integrating the results. CONCLUSION: The combination of metabonomics and systematic pharmacology based on LC-MS is feasible and effective, which provides strong support for exploring the effective components and pharmacological mechanism of TCM.
Subject(s)
Diabetes Mellitus, Type 2 , Drugs, Chinese Herbal , Pueraria , Salvia miltiorrhiza , Humans , Diabetes Mellitus, Type 2/metabolism , Salvia miltiorrhiza/chemistry , Pueraria/chemistry , Network Pharmacology , Metabolomics/methods , Drugs, Chinese Herbal/pharmacologyABSTRACT
BACKGROUND: The mortality following ST-segment elevation myocardial infarction (STEMI) remains substantial in the reperfusion era. Shenfu injection, as a traditional Chinese herbal formula, can alleviate ischemia-reperfusion injury through multiple pharmacologic effects. However, no robust data are available regarding the role of Shenfu injection in reducing infarct size for patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). METHODS/DESIGN: This RESTORE trial is a multicenter, randomized, double-blind, parallel-group, placebo-controlled trial (NCT04493840). A total of 326 eligible patients with first-time anterior STEMI undergoing PPCI within 12 h of symptom onset will be enrolled from 10 centers in mainland China. Patients are randomized in a 1:1 fashion to receive either intravenous Shenfu injection (80mL Shenfu injection + 70mL 5% glucose injection) or placebo group (150mL 5% glucose injection) before reperfusion and followed by once a day until 5 days after PPCI. The primary end point is infarct size assessed by cardiac magnetic resonance (CMR) imaging 5±2 days after PPCI. The major secondary end points include enzymatic infarct size, microvascular obstruction, intramyocardial hemorrhage, left ventricular volume and ejection fraction assessed by CMR, as well as cardiovascular events at 30 days. CONCLUSIONS: The RESTORE trial is sufficiently powered to demonstrate the clinical effects of Shenfu injection on myocardial injury in STEMI patients undergoing PPCI in the contemporary era.
Subject(s)
Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/diagnosis , Percutaneous Coronary Intervention/methods , Magnetic Resonance Imaging , Double-Blind Method , Treatment OutcomeABSTRACT
Aconitum carmichaelii Debeaux is a traditional Chinese medicinal herb that has been utilized for approximately 2,000 years. However, as cultivation has increased, there have been more reports of A. carmichaelii infections caused by four major pathogenic fungal species, Fusarium oxysporum, F. solani, Mucor circinelloides, and Sclerotium rolfsii, resulting in increased disease incidences and limited production and quality. To detect these infections, we developed a LAMP-based toolbox in this study. The cytochrome c oxidase subunit 1 (cox1) gene, translation elongation factor-1α (EF-1α), internal transcribed spacer (ITS) regions of rDNA, and alcohol dehydrogenase 1 (ADH1) gene, respectively, were used to design species-specific LAMP primer sets for F. oxysporum, F. solani, S. rolfsii, and M. circinelloides. The results showed that the LAMP-based toolbox was effective at detecting pathogens in soil and plant materials. We also used this toolbox to investigate pathogen infection in the main planting regions of A. carmichaelii. Before harvesting, F. oxysporum, M. circinelloides, and S. rolfsii were commonly found in the planting fields and in infected A. carmichaelii plants. Therefore, the toolbox we developed will be useful for tracking these infections, as well as for disease control in A. carmichaelii.
Subject(s)
Aconitum , Aconitum/microbiologyABSTRACT
This study aims to investigate the efficacy of forsythiaside A(FTA) against CCl_4-induced liver fibrosis and the mechanism. Specifically, activities of serum alanine/aspartate aminotransferase(ALT/AST) and hydroxyproline(HYP) level in liver were detected, and pathological morphology of liver was observed based on hematoxylin-eosin(HE) staining, Masson's trichrome staining, and Sirius red staining of liver. On this basis, the effect of FTA on liver fibrosis was evaluated. The mRNA expression of actin alpha 2/α-smooth muscle actin(Acta2/α-SMA), transforming growth factor ß(Tgfß), collagen â alpha 1(Col1 a1), and collagen â ¢ alpha 1(Col3 a1) in liver tissue and hepatic stellate cells(HSC) was determined by qPCR, and the protein expression of α-SMA in liver tissue and HSC was measured by Western blot to assess the inhibition of FTA on HSC activation. The protein expression of α-SMA, vi-mentin(Vim), vascular endothelial cadherin(Ve-cadherin), and platelet endothelial cell adhesion molecule-1(PECAM-1/CD31) was measured by Western blot to evaluate the reverse of endothelial-mesenchymal transition(EMT) by FTA. The efficacy of FTA in relieving CCl_4-induced liver fibrosis was evidenced by the alleviation of hepatocyte necrosis, liver inflammation, and hepatic collagen deposition. FTA decreased the mRNA expression of Acta2, Tgfß, Col1 a1, and Col3 a1 and protein expression of α-SMA both in vivo and in vitro. FTA reversed the increase of α-SMA and Vim and the decrease of CD31 and Ve-cadherin in livers from mice treated with CCl_4. Therefore, FTA alleviated CCl_4-induced liver fibrosis in mice via suppressing HSC activation and reversing EMT.
Subject(s)
Glycosides , Liver Cirrhosis , Animals , Mice , Actins/genetics , Actins/metabolism , Alanine Transaminase/blood , Carbon Tetrachloride/toxicity , Carbon Tetrachloride/metabolism , Collagen/metabolism , Hepatic Stellate Cells , Liver/drug effects , Liver Cirrhosis/chemically induced , Liver Cirrhosis/drug therapy , Liver Cirrhosis/genetics , RNA, Messenger/metabolism , Transforming Growth Factor beta/metabolism , Glycosides/therapeutic useABSTRACT
Electromagnetic Field (EMF) influences melanoma in various ways. EMF can be classified into extremely low-frequency electromagnetic field, low-frequency magnetic field, static moderate magnetic field, strong electromagnetic field, alternating magnetic field, and magnetic nanoparticles. Each type of EMF influences melanoma development differently, and the detailed influence of each specific type of EMF on melanoma is reviewed. Furthermore, EMF influences melanoma cell polarity and hence affects drug uptake. In this review, the impacts of EMF on the effectiveness of drugs used to treat melanoma are listed according to drug types, with detailed effects according to the types of EMF and specific melanoma cell lines. EMF also impacts clinical therapies of melanoma, including localized magnetic hyperthermia, focalized thermotherapy, proton radiation treatment, nanostructure heating magnetic hyperthermia, radiation therapy, Polycaprolactone-Fe3O4 fiber mat-based bandage, and optune therapy. Above all, EMF has huge potential in melanoma treatment.
ABSTRACT
Objective: To analyze the mechanism of LINC00461 regulating the recurrence of diffuse large B cell lymphoma (DLBCL) through microRNA (miR)-411-5p/BCL2 interacting protein 3 (BNIP3) pathway. Methods: DLBCL samples in TCGA and GSE12453 were used for differential analysis to find long noncoding RNA (lncRNA) related to DLBCL recurrence. The 4 DLBCL data with the highest and lowest expression levels of LINC00461 in the TCGA database were selected for GSEA enrichment analysis. The targeting relationships of miR-411-5p with LINC00461 and BNIP3 were verified by the dual luciferase report. Blood samples from DLBCL patients were used to analyze the correlation between miR-411-5p and LINC00461 or BNIP3. LINC00461, miR-411-5p, or BNIP3 was overexpressed or silenced by transfection, and a tumor-bearing nude mice model was constructed to detect their effects on proliferation and apoptosis. Results: The level of LINC00461 in DLBCL was significantly higher than that in normal cases, and the level in recurrence DLBCL was significantly higher than that in nonrecurrence. The enrichment analysis results showed that the function of LINC00461 was closely related to apoptosis. The results shown that miR-411-5p bound to LINC00461 and BNIP3 and was negatively correlated with LINC00461 and BNIP3 mRNA in blood of DLBCL patients. Suppressing the level of LINC00461 inhibited cell proliferation and induced apoptosis. The inhibition of LINC00461 or overexpression of miR-411-5p reduced the expression of BNIP3 protein, thereby inducing apoptosis at the in vivo and in vitro levels. Conclusion: LINC00461 may induce miR-411-5p to "sponge," thereby increasing the expression of BNIP3 protein, and exerting the function of inhibiting apoptosis and promoting DLBCL recurrence.
ABSTRACT
BACKGROUND: With the advantages of miniature damage and optimal effectiveness, percutaneous coronary intervention (PCI) has been performed in a large number of coronary artery disease patients. However, recent studies have indicated a higher incidence of depression on post-PCI patients. Acupuncture therapy is effective for depression. As a form of acupuncture, the auricular acupuncture has been used to relieve symptoms in patients with post-PCI depression, but its effectiveness and safety have not yet reached a definitive conclusion. Therefore, this systematic review and meta-analysis protocol is planned to evaluate the efficacy and safety of auricular acupuncture for depression in post-PCI patients. METHODS: Six English databases (PubMed, Web of Science, MEDLINE, EMBASE, Springer Cochrane Library, and WHO International Clinical Trials Registry Platform) and 4 Chinese databases (Wan Fang Database, Chinese Scientific Journal Database, China National Knowledge Infrastructure Database, and Chinese Biomedical Literature Database) will be searched normatively according to the rule of each database from the inception to February 1, 2022. Two reviewers will independently conduct article selection, data collection, and risk of bias evaluation. Any disagreement will be resolved by discussion with the third reviewer. Either the fixed-effects or random-effects model will be used for data synthesis based on the heterogeneity test. The change in the scores on the Hamilton Depression Scale and the Self-rating Depression Scale will be used as the main outcome measure. All-cause mortality, cardiac mortality, major adverse cardiovascular events, rehospitalisation rate, and Quality of Life Scale as the secondary outcome. Treatment Emergent Symptom Scale, general physical examination (temperature, pulse, respiration, blood pressure), routine examination of blood, urine and stool, electrocardiogram, liver and kidney function examination as the security indexes. RevMan 5.3.5 will be used for meta-analysis. RESULTS: This study will provide high-quality evidence to assess the efficacy and safety of auricular acupuncture for depression in post-PCI patients. CONCLUSION: This systematic review will explore whether auricular acupuncture is an effective and safe intervention for depression in post-PCI patients. INPLASY REGISTRATION NUMBER: INPLASY202230003.
Subject(s)
Acupuncture, Ear , Percutaneous Coronary Intervention , Depression/etiology , Depression/therapy , Humans , Meta-Analysis as Topic , Percutaneous Coronary Intervention/adverse effects , Quality of Life , Systematic Reviews as TopicABSTRACT
Relapse as the commonest treatment failure through chemotherapy of child presented with acute lymphoblastic leukemia (ALL) is usually within 3 years of remission. Central nervous system (CNS) is expected as a site of extramedullary relapse in 3-8% of child leukemia, often leading to a poor prognosis. A few patients may have headache and vomiting and can be diagnosed without difficulty. However, most patients present with asymptomatic conditions. Obesity has become one of the greatest reported complications of children ALL survivors. Rarely, obesity presentation can be the first manifestation of CNS leukemia. Here, we present three unusual cases with B-ALL presentation of obesity as the first symptom at the time of CNS relapse after achieving remission. This highly localized presentation is unusual and would hopefully inform clinicians to have a high index of suspicion for relapse in children with ALL.
ABSTRACT
As a life-threatening disease, stroke is the leading cause of death and also induces adult disability worldwide. To investigate the efficacy of the integrated traditional Chinese medicine (ITCM) on the therapeutic effects of acute ischemic stroke (AIS) patients, we enrolled 26 patients in the ITCM [Tanhuo decoction (THD) + Western medicine (WM)] group and 23 in the WM group. Thirty healthy people were also included in the healthy control (HC) group. ITCM achieved better functional outcomes than WM, including significant reduction of the phlegm-heat syndrome and neurological impairment, and improvement of ability. These facts were observed in different pretreatment gut enterotypes. In this paper, we collected the stool samples of all participants and analyzed the 16S rRNA sequence data of the gut microbiota. We identified two enterotypes (Type-A and Type-B) of the gut microbial community in AIS samples before treatment. Compared to Type-B, Type-A was characterized by a high proportion of Bacteroides, relatively high diversity, and severe functional damage. In the ITCM treatment group, we observed better clinical efficacy and positive alterations in microbial diversity and beneficial bacterial abundance, and the effect of approaching healthy people's gut microbiota, regardless of gut enterotypes identified in pretreatment. Furthermore, we detected several gut microbiota as potential therapeutic targets of ITCM treatment by analyzing the correlations between bacterial abundance alterations and functional outcomes, where Dorea with the strongest correlation was known to produce anti-inflammatory metabolite and negatively linked to trimethylamine-N-oxide (TMAO), a biomarker of AIS. This study analyzed clinical and gut microbial data and revealed the possibility of a broad application independent of the enterotypes, as well as the therapeutic targets of the ITCM in treating AIS patients with phlegm-heat syndrome.
Subject(s)
Gastrointestinal Microbiome , Ischemic Stroke , Microbiota , Adult , Humans , Ischemic Stroke/drug therapy , Medicine, Chinese Traditional , RNA, Ribosomal, 16S/geneticsABSTRACT
Acute ischemic stroke (AIS) is a major cause of acquired adult disability and death. Our previous studies proved the efficacy and effectiveness of Tanhuo decoction (THD) on AIS. However, the therapeutic mechanism remains unclear. We recruited 49 AIS patients and 30 healthy people to explore the effects of THD+basic treatment on the poststroke gut microbiota of AIS patients using 16S rRNA sequencing, in which 23 patients received basic treatment (control group) and 26 patients received THD+basic treatment (THD group). By comparing the data before and after treatments, we found the THD group acquired better outcome than the control group on both clinical outcome indices and the characteristics of gut microbiota. In addition to the mediation on short-chain fatty acid- (SCFA-) producing bacteria in two groups, treatment in the THD group significantly decreased the lipopolysaccharide- (LPS-) producing bacteria to reduce LPS biosynthesis. Besides, the complexity of the cooccurrence of gut microbiota and the competition among LPS-producing bacteria and opportunistic pathogenetic bacteria were enhanced in the THD group. Treatment in the THD group also exhibited the potential in decreasing genes on the biosynthesis of trimethylamine (TMA), the precursor of Trimethylamine N-oxide (TMAO), and increasing genes on the degradation of TMA, especially increasing trimethylamine-corrinoid protein Co-methyltransferase (mttB) which catabolizes TMA to methane. These results hinted that THD+basic treatment might exert its efficacy by mediating the gut microbiota and microbial metabolites, including LPS and TMAO that aggravate the sterile inflammation and platelet aggregation. Moreover, the well-fitting regression model results in predicting the clinical outcome with the alteration of gut microbiota proved gut microbiota as a potential indicator of AIS and provided evidence of the communication between the gut and brain of AIS patients.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Gastrointestinal Microbiome/drug effects , Ischemic Stroke/drug therapy , Ischemic Stroke/microbiology , Acute Disease , Case-Control Studies , Humans , Prospective Studies , Treatment OutcomeABSTRACT
PROBLEM IDENTIFICATION: The aim of this article is to evaluate the effectiveness of yoga on cancer-related fatigue (CRF) in patients undergoing chemotherapy and/or radiation therapy. LITERATURE SEARCH: Relevant English and Chinese articles were retrieved from medical databases and included in this analysis. Standardized critical appraisal instruments from the Joanna Briggs Institute were adopted for the quality assessment. DATA EVALUATION: 16 randomized controlled trials met the inclusion criteria. SYNTHESIS: Yoga interventions had a positive effect in reducing CRF among patients undergoing chemotherapy and/or radiation therapy, but the adherence to yoga was low. Mixed types of yoga, in addition to supervised and self-practicing strategies, were associated with increased patient adherence and improved CRF. IMPLICATIONS FOR PRACTICE: Yoga appears to be a safe and effective exercise for the management of CRF during chemotherapy and/or radiation therapy; however, additional high-quality studies are needed to define an optimal yoga intervention strategy.
Subject(s)
Meditation , Neoplasms , Yoga , Fatigue/etiology , Fatigue/therapy , Humans , Neoplasms/complications , Neoplasms/therapy , Patient ComplianceABSTRACT
BACKGROUND: Masked hypertension is associated with adverse cardiovascular outcomes. Nonetheless, no randomized controlled trials exist in the treatment of masked hypertension. The aim of this randomized, placebo-controlled trial was to investigate the efficacy and safety of blood pressure (BP)-lowering treatment with a Chinese herbal formula, gastrodia-uncaria granules, in patients with masked hypertension. METHODS: Patients with an office BP of <140/90 mm Hg and daytime ambulatory BP of 135 to 150 mm Hg systolic or 85 to 95 mm Hg diastolic were randomly assigned 1:1 to the treatment of gastrodia-uncaria granules or placebo 5 to 10 g twice daily for 4 weeks. The primary efficacy variable was the change in daytime ambulatory BP. RESULTS: At baseline, office and daytime BP of the 251 participants (mean age, 50.4 years; 53.4% men; mean body mass index 24.5 kg/m2; and 2.8%, 1.6%, and 30.7% with cardiovascular disease, diabetes, and smoking, respectively) averaged 129/82 and 135/89 mm Hg, respectively. In the intention-to-treat analysis, daytime systolic/diastolic BP was reduced by 5.44/3.39 and 2.91/1.60 mm Hg in the gastrodia-uncaria granules and placebo groups, respectively. The between-group difference in BP reductions was significant for the daytime (2.52/1.79 mm Hg; P≤0.025) and 24-hour BP (2.33/1.49 mm Hg; P≤0.012), but not for the clinic and nighttime BPs (P≥0.162). The per-protocol analysis in 229 patients produced similar results. Only 1 adverse event (sleepiness during the day) was reported, and no serious adverse event occurred. CONCLUSIONS: BP-lowering treatment with Chinese traditional medicine gastrodia-uncaria granules is efficacious for patients with masked hypertension. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02156024.
Subject(s)
Antihypertensive Agents/administration & dosage , Blood Pressure Monitoring, Ambulatory , Blood Pressure/drug effects , Drugs, Chinese Herbal/administration & dosage , Masked Hypertension , Adult , China , Female , Humans , Male , Masked Hypertension/drug therapy , Masked Hypertension/physiopathology , Middle AgedABSTRACT
Corydalis Bungeanae Herba is often used to treat a variety of inflammatory diseases in traditional Chinese medicine. In order to determine its chemical material basis, the components of Corydalis Bungeanae Herba were isolated by automated purification system. Flavonoids and alkaloids were prepared, and all such components were identified by mass spectrometry. The effects of the components on the production of inflammatory mediators and pharmacological mechanisms in the lipopolysaccharide(LPS)-induced RAW264.7 cell inflammation model were examined. Mouse macrophages(RAW264.7) were first treated with LPS. The relationship between cell viability and LPS concentration was observed. Then, the effects of flavonoids components and alkaloid components with different administration concentrations on cell viability were detected to determine the maximum administration concentration. Secondly, 2.5, 5, 10 and 20 µg·mL~(-1) flavonoids components and alkaloid components were added respectively to observe the effects and mechanism of different concentrations of flavonoids components and alkaloid components on LPS-induced inflammation of RAW264.7 macrophages. Griess reagent assay was used to detect NO content in cell supernatant. The inflammatory cytokines(TNF-α, IL-1ß and IL-6) in cell supernatant were determined by ELISA method. Western blot method was used to detect the intracellular nuclear factor(NF-κB) IκBα phosphorylation(p-IκBα), p65 phosphorylation(p-p65) and protein expression of TLR4, TLR2. The results showed that the alkaloid components inhibited the production of NO, TNF-α, IL-1ß and IL-6 in a dose-dependent mannerin the concentration range of 2.5-20 µg·mL~(-1). In inflammation upstream pathways, the inhibitory effect of the alkaloid components on the TLR2 expression level was weaker than that of TLR4. In inflammation downstream, alkaloid components significantly inhibited phosphorylation of IκBα and p65 in a dose-dependent manner. These data suggested that the alkaloid components were the material basis components of Corydalis Bungeanae Herba, and its anti-inflammatory mechanism might be related to inhibiting the transmission of inflammatory signals in TLRs/NF-κB signaling pathways dominated by TLR4, interfering with the activation of inflammatory genes and inhibiting their over expression, and down-regulating the secretion level of inflammatory factors.
Subject(s)
Corydalis , Animals , Anti-Inflammatory Agents/therapeutic use , Inflammation/drug therapy , Lipopolysaccharides , Mice , NF-kappa B , RAW 264.7 CellsABSTRACT
Immobilized liposome chromatography (ILC) is a powerful tool in screening and analyzing membrane-permeable components in natural medicinal herbs. In this study, the stationary phase of a new receptor liposome biomembrane chromatography (RLBC) was employed to screen the active ingredients in seven natural medicinal herbs. As a model system, α-glucosidase was immobilized in porous silica gel by incorporating α-glucosidase into liposome vesicles. Combined with HPLC, this stationary phase can be used to evaluate the interaction of liposome-protein compounds with compounds and drugs. The surface characteristics of the RLBC phase was characterized by Scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR) and Energy dispersive spectrometer (EDS). RLBC was successfully used to screen and analyze permeable compounds in natural medicinal herbs, and screen the extracts from Schisandra chinensis. This method was used to establish that Schisandrin in Schisandra chinensis is an active component. Furthermore, the hypoglycemic effect of Schisandrin was verified in vivo in rats. This study further modeled the relationship between the activity of inhibitor and retention behavior with RLBC with a mathematical equation. RLBC stationary phase combined with HPLC can be used for rapid screening of drug candidates.
ABSTRACT
BACKGROUND: Vitamin E, which is critically important in the whole process of reproduction, can antagonize the oxidative stress caused by the oxygen free radicals and antioxidant imbalance and regulate normal physiological function of the reproductive system. The effect of short-term supplementation of vitamin E on outcomes of infertile women with polycystic ovary syndrome (PCOS) when they underwent ovulation induction with clomiphene citrate (CC) and human menopausal gonadotropin (HMG) remains unknown. METHODS: This was a retrospective cohort clinical trial from October 2015 to April 2017. A total of 321 PCOS cases underwent ovulation induction with CC and HMG. Patients in group A (n = 110) did not receive vitamin E while patients in group B (n = 105) and group C (n = 106) received oral treatment of vitamin E at 100 mg/day during follicular phase and luteal phase, respectively. RESULTS: It was observed no significant differences of ovulation rate, clinical pregnancy rate, and ongoing pregnancy rate among the three groups. It was interesting that dosage of HMG were significant lower in group B compared with those in group A and group C (P<0.05). CONCLUSIONS: A short-term supplementation of vitamin E can improve oxidative stress, and reduce exogenous HMG dosage to lower the economic cost with a similar pregnancy rate in the ovulation induction cycle. However, the supplementation does not alter the pregnancy rate in the ovulation induction cycle. TRIAL REGISTRATION: ChiCTR-OOC-14005389, 2014.