Exploring the molecular mechanism of Ling-Gui-Zhu-Gan decoction for the treatment of type 2 diabetes mellitus based on network pharmacology and molecular docking: A review.

To investigate the mechanism of action of the classical formula Ling-Gui-Zhu-Gan (LGZG) decoction in treating type 2 diabetes mellitus based on network pharmacology and molecular docking. The active ingredients and targets of LGZG decoction were collected by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database and mapped using Cytoscape software to show their interrelationships. GeneCards, Pharmacogenomics Knowledge Base, OMIM, Therapeutic Target Database, and Drugbank databases were used to obtain targets related to type 2 diabetes; protein-protein interaction networks were established with the help of the STRING platform. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed on selected core targets with the help of the Metascape platform. Finally, the AutoDock platform was used to perform molecular docking and display the results by Pymol software. One hundred twenty-one active ingredients, 216 effective target genes, 11,277 type 2 diabetes mellitus-related genes, 210 crossover genes, and 18 core genes were obtained for LGZG decoction. The results obtained by Kyoto Encyclopedia of Genes and Genomes indicated that the advanced glycosylation end products-receptor of advanced glycosylation end products signaling pathway, the phosphatidylinositol 3 kinase-Akt signaling pathway, and HIF-1 signaling pathway might be the key signaling pathways. Molecular docking showed that the binding energy of quercetin, kaempferol, naringenin, and licorice chalcone A to the core target genes were all <5.0 kJ-mol-1, with good affinity. In this study, the potential active ingredients and mechanisms of action of LGZG decoction in the treatment of type 2 diabetes were initially investigated, which provided a basis for the in-depth study of its drug basis and mechanisms of action.

Effects of galactooligosaccharides on maternal gut microbiota, glucose metabolism, lipid metabolism and inflammation in pregnancy: A randomized controlled pilot study.

Background: Gut microbiota of pregnant women change with the gestational week. On the one hand, they participate in the metabolic adaptation of pregnant women. On the other hand, the abnormal composition of gut microbiota of pregnant women is more likely to suffer from gestational diabetes mellitus (GDM). Therefore, gut microbiota targeted treatment through dietary supplements is particularly important for prevention or treatment. Prebiotic supplements containing galactooligosaccharides (GOS) may be an intervention method, but the effect is still unclear. Objective: This study aims to evaluate the feasibility and acceptability of prebiotic intervention in healthy pregnant women during pregnancy, and to explore the possible effects of intervention on pregnant women and the influence on gut microbiota as preliminaries. Methods: After recruitment in first trimester, 52 pregnant women were randomly assigned to receive GOS intervention or placebo containing fructooligosaccharides. 16S rRNA sequencing technology was used to detect the composition, diversity and differential flora of gut microbiota. Lipid metabolism, glucose metabolism and inflammatory factors during pregnancy were also analyzed. Results: The adverse symptoms of GOS intervention are mild and relatively safe. For pregnant women, there was no significant difference in the GDM incidence rates and gestational weight gain (GWG) in the GOS group compared with placebo (P > 0.05). Compared with the placebo group, the levels of FPG, TG, TC, HDL-C LDL-C, and IL-6 had no significant difference in GOS group (P > 0.05). For newborns, there was no significant difference between GOS group and placebo group in the following variables including gestational week, birth weight, birth length, head circumference, chest circumference, sex, and delivery mode (P > 0.05). And compared with the placebo group, the GOS group had a higher abundance of Paraprevotella and Dorea, but lower abundance of LachnospiraceaeUCG_001. Conclusions: GOS prebiotics appear to be safe and acceptable for the enrolled pregnancies. Although GOS intervention did not show the robust benefits on glucose and lipid metabolism. However, the intervention had a certain impact on the compostion of gut microbiota. GOS can be considered as a dietary supplement during pregnancy, and further clinical studies are needed to explore this in the future.

Sleep among Obstetrics and Gynecology Trainees: Results from a Yoga-Based Wellness Initiative.

OBJECTIVE: This study aimed to determine the feasibility of using a wrist-based fitness tracking device to assess sleep among Obstetrics and Gynecology (OBGYN) trainees who engaged in a yoga-based wellness program. We also sought to evaluate the effects of yoga on sleep. STUDY DESIGN: A quality improvement initiative consisting of an 8-week wellness program of weekly yoga classes, nutrition, and physical challenges was implemented for OBGYN residents and Maternal-Fetal Medicine fellows. The Polar A370 fitness tracker device was provided and synced to the Polar Flow for Coach program for inclusion. Data obtained included total and restful sleep from each night the device were worn. Pre- and post-assessment of the Pittsburg Sleep Quality Index (PSQI) were compared. Linear mixed models were used to estimate and test the effect of yoga on sleep while controlling for on-call shifts. RESULTS: Of the 15 participants who synced their device, 13 (87%) were included for analysis. Sleep data from 572 nights were analyzed. The mean (SD) total sleep was 434.28 (110.03) minutes over the 8 weeks. A minimum of 7 hours (420 minutes) of total sleep occurred 59.3% of the time. After controlling for Friday or Saturday night on-call, those who attended yoga class had a significantly greater total sleep (yoga: 425.14 minutes [41.89], no yoga: 357.33 [43.04] minutes; p = 0.04). There was no significant change in the mean global PSQI score after the program (pre: 5.0 [1.6], post: 5.1 [2.5], p = 0.35). CONCLUSION: Wearable fitness monitors provide insight into sleep patterns displayed during training and can serve as a tool to identify those who are sleep deprived and assist in the evaluation of trainee wellness. Training programs are encouraged to provide access to yoga and mindfulness interventions to improve sleep and possibly clinical performance. KEY POINTS: · Yoga improves trainee sleep by approximately 60 minutes.. · Total and restful sleep are reduced during night float rotation.. · Trainees obtained 7 hours of sleep approximately 60% of the time..

Dextrose Prolotherapy for Symptomatic Grade IV Knee Osteoarthritis: A Pilot Study of Early and Longer-Term Analgesia and Pain-Specific Cytokine Concentrations.

Background: Neurocytokines may upregulate or downregulate neuropathic pain. We hypothesized that dextrose (D-glucose) injections for therapeutic purposes (dextrose prolotherapy: DPT) in painful knee osteoarthritis (KOA) would favorably affect synovial-fluid neurocytokine concentrations. Methods: Twenty participants with grade IV symptomatic KOA received synovial-fluid aspiration followed by dextrose or simulated dextrose injections, followed by the reverse after one week. All participants then received open-label dextrose injections monthly for 6 months, with serial assessments of walking pain at 20 min for 9 months, as well as synovial-neurocytokine-concentration measurements (calcitonin gene-related peptide, substance P (SP), and neuropeptide Y (NPY)) at one week and three months. Results: Clinically important analgesia was observed at 20 min and for 9 months post dextrose injection. One -week synovial-fluid SP concentration rose by 111% (p = 0.028 within groups and p = 0.07 between groups) in the dextrose-injected knees compared to synovial-fluid aspiration only. Three-month synovial-fluid NPY concentration dropped substantially (65%; p < 0.001) after open-label dextrose injection in all knees. Conclusions: Prompt and medium-term analgesia after intra-articular dextrose injection in KOA was accompanied by potentially favorable changes in synovial-fluid neurocytokines SP and NPY, respectively, although these changes were isolated. Including neurocytokines in future assessments of DPT to elucidate mechanisms of action is recommended.

Comparative Analysis of the Metabolites and Biological Activity of Cultivated and Wild Lignosus rhinocerotis.

In this paper, Lignosus rhinocerotis (Cooke) Ryvarden (L. rhinocerotis) cultivated in rice medium (LRR) and in sawdust medium (LRS) was harvested. Then, in terms of the LRR, LRS, and wild L. rhinocerotis (LRW), the total flavonoid contents, total polyphenol contents, total polysaccharide contents, and metabolites were detected; antioxidants of their aqueous extracts and anti-inflammatory of their polysaccharides were performed. In addition, the possible mechanism of the polysaccharides of L. rhinocerotis inhibiting lung damage was elucidated. The results showed that 32 compounds were characterized in L. rhinocerotis, including flavonoids, terpenoids, lignans, and steroids and there were 20 compounds in cultivated and wild L. rhinocerotis; LRR has the highest total polyphenol and flavonoid contents, as well as ABTS and DPPH scavenging capacity. The total polysaccharide contents and the FRAP scavenging capacity of wild L. rhinocerotis were higher than those of cultivated L. rhinocerotis. The inhibition of polysaccharides of LRW (PLRW) on LPS-induced MRC-5 damage was stronger than that of the polysaccharides from cultivated L. rhinocerotis. The PLRW may alleviate lung damage by inhibiting the NLRP3 pathway and thereby suppressing the inflammatory response. In summary, both cultivated and wild L. rhinocerotis are abundant in bioactive components and have antioxidant and anti-inflammatory activities.

Morroniside, a novel GATA3 binding molecule, inhibits hepatic stellate cells activation by enhancing lysosomal acid lipase expression.

BACKGROUND: Liver fibrosis can be easily developed into irreversible liver cirrhosis or even liver cancer. Lysosomal acid lipase (LAL), encoded by the lipase A (Lipa) gene, is a critical enzyme involved in liver fibrosis development. Morroniside, an iridoid glycoside isolated from Cornus officinalis Sieb. et Zucc., exerts hepatic protective effects. However, the mechanism of action underling the anti-liver fibrosis effects of morroniside have not been fully elucidated. PURPOSE: To explore whether Lipa served as a biomarker for liver fibrosis and investigate the anti-liver fibrosis effects of morroniside and the underlying action mechanism in liver fibrosis cell models. METHODS: LAL expression was examined in the liver tissues of CCl4 and high-fat diet (HFD)-induced liver fibrosis animal models. α-smooth muscle actin (α-SMA) level, collagen and GATA family expressions were analyzed by Real-time PCR and Western blot. Putative transcription factor binding sites in the DNA sequences of Lipa was identified by PROMO-ALGGEN v8.3 online software and ENCODE ChIP-Seq Significance Tool. MD simulation was performed to explore the protein-ligand interaction. RESULTS: We found that the expression of hepatic LAL is lower in the liver fibrosis animal models than the control models. The reduced LAL expression is associated with HSCs activation, suggesting LAL is novel liver fibrosis biomarker. More importantly, our data showed that morroniside exerts anti-liver fibrosis effects in vitro. Mechanistic studies reveal that it binds to the hydrophobic sites of GATA3 and also reduces GATA3 expression, which increases LAL expression. CONCLUSIONS: This study, for the first time, suggests LAL is a novel biomarker for liver fibrosis. Besides, morroniside exerts its anti-liver fibrosis effects by targeting GATA3 and LAL and hence inhibits HSC activation. These findings provide strong scientific evidence to support the development of morroniside as novel alternative or complementary therapeutics for liver injury prevention and treatment.

Dextrose Effects on Platelet Count and Volume: Implications for Regenerative Medicine.

Platelet-rich plasma (PRP) and hypertonic dextrose solutions are commonly used injectates in regenerative medicine, sometimes used simultaneously. The effects of hypertonic dextrose on platelet lysis and activation have not been previously reported. We tested the effects of escalating dextrose concentration on cell counts and cell volume of platelets and red cells in PRP and whole blood (WB). A prompt partial reduction in platelet count occurred with all dextrose admixtures with either PRP or whole blood, consistent with partial lysis. After the first minute, platelet counts remained stable, suggesting a rapid accommodation of residual platelets to extreme (>2000 mOsm) hypertonicity. A 25% or higher dextrose concentration caused a significant increase in mean platelet volume (MPV), which suggests an early phase of platelet activation. Further investigation is warranted to confirm if platelet lysis or activation has occurred and whether additive clinical benefit may result from hypertonic dextrose injection alone or in combination with PRP.

Spatial Assessment of Heterogeneous Tissue Natural Frequency Using Micro-Force Optical Coherence Elastography.

Analysis of corneal tissue natural frequency was recently proposed as a biomarker for corneal biomechanics and has been performed using high-resolution optical coherence tomography (OCT)-based elastography (OCE). However, it remains unknown whether natural frequency analysis can resolve local variations in tissue structure. We measured heterogeneous samples to evaluate the correspondence between natural frequency distributions and regional structural variations. Sub-micrometer sample oscillations were induced point-wise by microliter air pulses (60-85 Pa, 3 ms) and detected correspondingly at each point using a 1,300 nm spectral domain common path OCT system with 0.44 nm phase detection sensitivity. The resulting oscillation frequency features were analyzed via fast Fourier transform and natural frequency was characterized using a single degree of freedom (SDOF) model. Oscillation features at each measurement point showed a complex frequency response with multiple frequency components that corresponded with global structural features; while the variation of frequency magnitude at each location reflected the local sample features. Silicone blocks (255.1 ± 11.0 Hz and 249.0 ± 4.6 Hz) embedded in an agar base (355.6 ± 0.8 Hz and 361.3 ± 5.5 Hz) were clearly distinguishable by natural frequency. In a beef shank sample, central fat and connective tissues had lower natural frequencies (91.7 ± 58.2 Hz) than muscle tissue (left side: 252.6 ± 52.3 Hz; right side: 161.5 ± 35.8 Hz). As a first step, we have shown the possibility of natural frequency OCE methods to characterize global and local features of heterogeneous samples. This method can provide additional information on corneal properties, complementary to current clinical biomechanical assessments, and could become a useful tool for clinical detection of ocular disease and evaluation of medical or surgical treatment outcomes.

Effects of tai chi and qigong on rehabilitation after COVID-19: a protocol for systematic review and meta-analysis.

INTRODUCTION: COVID-19 is a public health emergency of international concern, which is characterised by rapid and widespread transmission, high mortality and complications. Several studies have shown the benefits of tai chi and qigong for recovery after COVID-19; however, no meta-analysis has been reported. Therefore, the purpose of this study is to evaluate the efficacy and safety of tai chi and/or qigong on rehabilitation after COVID-19 through a systematic review and meta-analysis to provide a reference and basis for clinical application. METHODS AND ANALYSIS: This study will use the Cochrane Library, PubMed, Web of Science, Embase, China Knowledge Network, China Biomedical Literature Database, Chinese Scientific Journal Database and Wanfang Database. The time period is from the inception of the database to November 2021, with no language restrictions. Searches will be conducted using the subject terms "Taichi","Qigong" and "COVID-19" plus free-text words. Articles will be screened and collected by two reviewers independently. Included studies will be assessed for quality using the Cochrane Risk of Bias Assessment Tool. Statistical analyses will be performed using the Revman V.5.3 software. The primary outcomes include 1-second forced expiratory volume and 1-second forced vital capacity, oxygen saturation, total white cell count and quality of life score. Secondary outcomes include time to remission of major symptoms, incidence of adverse events, clinical cure rate and mortality. Subgroup and sensitivity analyses will also be used to explore and interpret the heterogeneity. This protocol is written based on the guideline of the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocol. ETHICS AND DISSEMINATION: Ethical approval and consent are unnecessary because no primary data will be collected. The results will be disseminated through peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42021288962.

Yao medicine Amydrium hainanense suppresses hepatic fibrosis by repressing hepatic stellate cell activation via STAT3 signaling.

Ethnopharmacological relevance: Hepatic fibrosis (HF) occurs in response to chronic liver injury and may easily develop into irreversible liver cirrhosis or even liver cancer. Amydrium hainanense water extract (AHWE) is a water-soluble component extracted from the Yao medicine Amydrium hainanense (H.Li, Y.Shiao & S.L.Tseng) H.Li, which is commonly used for treating inflammatory diseases in folk. Previous evidence suggested that AHWE significantly inhibited hepatic stellate cell activation. However, little is known regarding the therapeutic effect of AHWE in HF and its underlying action mechanism. Objective: Investigation of the therapeutic effect of AHWE in HF and its underlying mechanism. Methods: The therapeutic effect of AHWE was tested in vivo using an HF mouse model via an intraperitoneal injection of carbon tetrachloride (CCl4). Histological evaluation of liver injury and fibrosis were tested by H&E staining and Masson's trichrome staining. Serum levels of ALT, AST, collagen type I (Col I), and hydroxyproline (HYP) were measured. The mRNA expression of liver fibrotic and inflammatory genes were tested, and the protein levels of alpha smooth muscle actin (α-SMA) and signal transducers and activators of transcription 3 (STAT3) were analyzed. The in vitro experiments were conducted using HSC-T6 and RAW264.7 cell lines. Results: Treatment with AHWE significantly reversed histopathological liver damage and liver function abnormalities in CCl4 mouse model. Also, the serum levels of ALT, AST, Col I, and HYP in CCl4-induced HF mice were improved in AHWE treatment. Further, AHWE showed a remarkable inhibitory effect on the expression of fibrosis markers (Acta2, Col1a1, and Col3a1) and inflammatory factors (Stat3, Tnfa, Il6, and Il1b) induced by CCl4. The results of in vitro experiments were consistent with those obtained in vivo. In addition, it is shown that STAT3 signaling was involved in the anti-fibrotic effects of AHWE as evidenced by STAT3 overexpression. Conclusion: The present study proposed a novel ethnomedicine for HF and suggested the underlying role of STAT3 signaling pathway regulation in this anti-fibrotic effect of the proposed medicine. These findings would serve as solid scientific evidence in support of the development of AHWE as a novel alternative or complementary therapy for HF prevention and treatment.

The Potential Antioxidant Activity and Characterization of Bioactive Compounds of Stahlianthus involucratus.

Stahlianthus involucratus (S. involucratus) has anti-inflammatory, antinociceptive, and antipyretic activities; however, there are no literature reports on its antioxidant capacity. This study presents a comparative assessment of the polyphenols contents, flavonoids contents, and antioxidant activity of the aqueous and methanol extracts of S. involucratus (ASI and MSI). Moreover, the expression of oxidative stress-related genes in H2O2-induced H9c2 cells pretreated with the MSI was measured by RT-qPCR, and furthermore, MSI were characterized by UHPLC-Q-Orbitrap-MS/MS. The results indicated that the MSI had higher antioxidant contents and antioxidant capacity, and MSI could inhibit H2O2-induced oxidative stress in H9c2 cells by activating the Nrf2/HO-1 pathway. UHPLC-Q-Orbitrap-MS/MS characterized 15 phenolic compounds from the MSI. In conclusion, S. involucratus has the potential antioxidant capacity.

Robustadial A and B from Eucalyptus globulus Labill. and their anticancer activity as selective tyrosyl-DNA phosphodiesterase 2 inhibitors.

Tyrosyl-DNA phosphodiesterase 2 (TDP2) is a recently discovered DNA repair enzyme that can repair topoisomerase 2-mediated DNA damage, resulting in cancer cell resistance. In this study, two compounds, robustadial A and B, were isolated from a fraction of the ethyl acetate extract of Eucalyptus globulus Labill. fruits based on TDP2 inhibition screening. The biological experiments indicated that robustadial A and B have TDP2 inhibitory activity with EC50 values of 17 and 42 µM, respectively, but no tyrosyl-DNA phosphodiesterase 1 inhibition at 100 µM. Robustadial A showed significant synergistic effects with the anticancer drug etoposide in four human cancer cell lines, non-small cell lung cancer cell line (A549), prostate cancer cell line (DU145), breast cancer cell line (MCF-7), colorectal adenocarcinoma cell line (HCT-116), and chicken lymphoma cell line (DT40), and chicken lymphoma cell line complementation with human TDP2 (DT40 hTDP2) with combination index values ranging from 0.21 to 0.74. This work will facilitate future efforts for the development of robustadial A-based TDP2 selective inhibitors.

Effect of auricular acupuncture on reduction of sertraline hydrochloride in patients with depression: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of auricular acupuncture on reduction rate of sertraline hydrochloride, and to explore the long-term efficacy of auricular acupuncture in patients with depression.@*METHODS@#Seventy-two patients with depression were randomly divided into an observation group (36 cases, 1 case dropped off) and a control group (36 cases, 2 cases dropped off). The patients in the control group were treated with conventional dosage reduction method, that is, the dosage of sertraline hydrochloride was reduced by 25% every week until the dosage was stopped completely on the premise of no aggravation of depressive symptoms. Based on the conventional dosage reduction method used in the control group, the patients in the observation group were treated with auricular acupuncture at Xin (CO@*RESULTS@#The dosage of sertraline hydrochloride in the observation group was less than that in the control group after 2, 3, 4 weeks of dosage reduction and during follow-up (@*CONCLUSION@#Auricular acupuncture could effectively reduce the dosage of sertraline hydrochloride, improve the dosage reduction rate, reduce the incidence of withdrawal syndrome and reduce the risk of long-term recurrence in patients with depression.

Therapeutic effect of acupuncture combined with wheat-grain moxibustion on perimenopausal depression with kidney deficiency and liver depression / 中国针灸

OBJECTIVE@#To compare the therapeutic effect of acupuncture combined with wheat-grain moxibustion and oral fluoxetine hydrochloride capsule on perimenopausal depression with kidney deficiency and liver depression.@*METHODS@#A total of 60 patients of perimenopausal depression with kidney deficiency and liver depression were randomized into an observation group and a control group, 30 cases in each one. Acupuncture combined with wheat-grain moxibustion were adopted in the observation group. Acupuncture was applied at Baihui (GV 20), Yintang (GV 29), Fengchi (GB 20), etc. for 30 min. Wheat-grain moxibustion was applied at Ganshu (BL 18), Shenshu (BL 23), Mingmen (GV 4) and Yongquan (KI 1), 3 moxa-cones for each acupoint. The treatment in the observation group was given once every 2 days, 3 times a week. Fluoxetine hydrochloride capsule was given orally in the control group, 20 mg each time, once a day. Treatment for 8 weeks was required in the both groups. The scores of Hamilton depression scale (HAMD) and modified Kupperman scale were observed in the both groups before and after treatment, and at 1, 3, 6-month follow-up. The therapeutic efficacy was evaluated after treatment.@*RESULTS@#Compared before treatment, the scores of HAMD and modified Kupperman scale after treatment and at each time point of follow-up were decreased in the both groups (@*CONCLUSION@#Acupuncture combined with wheat-grain moxibustion can effectively treat perimenopausal depression with kidney deficiency and liver depression, and have more stable and sustained therapeutic effect compared with oral fluoxetine hydrochloride capsule.

Lipophilic Extract and Tanshinone IIA Derived from Salvia miltiorrhiza Attenuate Uric Acid Nephropathy through Suppressing Oxidative Stress-Activated MAPK Pathways.

Uric acid nephropathy (UAN) is caused by excessive uric acid, which results in the damage of renal tissue via urate crystals deposition in the kidneys. The roots and rhizomes of Salvia miltiorrhiza Bunge (S. miltiorrhiza) have been clinically used in many prescriptions to treat uric acid-induced renal damage. This study investigates the uricosuric and nephroprotective effects of the ethyl acetate extract of S. miltiorrhiza (EASM) and tanshinone IIA (a major component of S. miltiorrhiza, Tan-IIA) on UAN and explores the underlying molecular mechanism. Both EASM and Tan-IIA significantly decreased serum uric acid (SUA), serum creatinine (SCR), urine uric acid (UUA), and increased urine creatinine (UCR), and blood urea nitrogen (BUN) levels in experimental UAN mice. In adenine and potassium oxonate-induced mice, EASM and Tan-IIA treatment alleviated renal dysfunction and downregulated the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Moreover, EASM treatment significantly prevented excessive reactive oxygen species (ROS) production in uric acid-induced HK-2 cells and suppressed the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). EASM also suppressed ROS-activated mitogen-activated protein kinases (MAPKs) in vivo and in vitro. These results suggest that both EASM and Tan-IIA demonstrated inhibitory effects on UAN through relieving NOX4-mediated oxidative stress and suppressing MAPK pathways activation.

Dextrose Prolotherapy Versus Lidocaine Injection for Temporomandibular Dysfunction: A Pragmatic Randomized Controlled Trial.

Objective: Several intraarticular injections, including dextrose and lidocaine, are reported to reduce pain and dysfunction in temporomandibular dysfunction (TMD) and increase maximal jaw opening; our goal was to determine whether dextrose/lidocaine outperforms sterile water/lidocaine for TMD. Design: Pragmatic randomized controlled trial. Setting: Outpatient clinic. Subjects: Chronic (≥3 months) of moderate-to-severe (≥6/10) jaw or facial pain meeting research-specific TMD criteria. Intervention: Blinded intraarticular dextrose prolotherapy (DPT) (20% dextrose/0.2% lidocaine) versus intraarticular lidocaine (0.2% lidocaine in sterile water) at 0, 1, and 2 months. Participants were then unblinded and offered DPT by request for 9 additional months. Main outcome measures: Primary: Numerical Rating Scale (0-10 points) score for facial pain and jaw dysfunction; percentage achieving ≥50% improvement in pain and dysfunction (0, 3, and 12 months). Secondary: Maximal interincisal opening (MIO; 0 and 3 months). Intention-to-treat analysis was by joint using mixed-model regression. Results: Randomization of 29 participants (25 female, 47 ± 17 years, 43 joints) produced similar groups. Three-month pain and dysfunction improvements were similar, but more DPT-treated joints improved by ≥50% in pain (17/22 vs. 6/21; p = 0.028). The MIO improved in both groups (5.6 ± 5.8 mm vs. 5.1 ± 7.0 mm; p = 0.70). From 3 to 12 months, minimal DPT was received by original DPT and lidocaine recipients, 0.5 ± 0.9 and 0.6 ± 1.5 injections, respectively, with only 2 out of 21 joints in the original lidocaine group receiving more than 1 dextrose injection after 3 months. Twelve-month analysis revealed that joints in the original DPT group improved more in jaw pain (4.8 ± 2.4 points vs. 2.6 ± 2.9 points; p = 0.026) and jaw dysfunction (5.3 ± 2.6 points vs. 2.7 ± 2.3 points; p = 0.013). More DPT than lidocaine-treated joints improved by ≥50% in both pain (19/22 vs. 5/21; p = 0.003) and dysfunction (17/22 vs. 7/21; p = 0.040). There were no adverse events; satisfaction was high. Conclusions: Intraarticular DPT resulted in clinically important and statistically significant improvement in pain and dysfunction at 12 months compared to lidocaine injection (ClinicalTrials.gov identifier NCT01617356).

Online couples mindfulness-based intervention for young breast cancer survivors and their partners: A randomized-control trial.

PURPOSE: Young breast cancer survivors (YBCS) face unique challenges in coping with disease, distress, and relationship concerns. The purposes of this study were to understand the acceptability and feasibility of an online Mindfulness-Based Intervention (MBI) for YBCS and their partners (i.e., Couples Mindfulness-Based Intervention: C-MBI) and to compare the effectiveness of the C-MBI to a closely-matched control, an online MBI for individuals (I-MBI). METHODS: YBCS and their partners were recruited. Couples were randomly assigned to an 8-week C-MBI (couples = 41) or to I-MBI (couples = 36), which included one-hour video modules, a manual, and guided-meditation audios. Both couple members participated in the C-MBI; only the YBCS participated in the control I-MBI. Participants answered surveys about individual- and couple-level functioning at baseline and post-intervention. RESULTS: Online delivery was shown to be feasible and acceptable. For YBCS and their partners, levels of perceived stress, anxiety, depression, and fatigue were lower after the intervention, in both conditions. Unexpectedly, however, participating in the C-MBI appeared to have detrimental effects on dyadic adjustment and relationship quality. CONCLUSION: Although YBCS and their partners reported online delivery was acceptable and benefited well-being, for couple-based MBIs to have benefits for relationship functioning, it may be necessary for couples to have the support of other couples and an instructor. Online delivery may be particularly acceptable and effective for clinical populations, including YBCS. Medical professionals may be more likely to recommend online-MBI programs to cancer survivors, because the programs are of little or no cost.

Sesquiterpenoids from the aerial parts of Conyza japonica and their inhibitory activity against nitric oxide production.

Four new sesquiterpenoids, conyterpenols A - D (1-4), along with nineteen known analogues (5-23) were isolated from the aerial parts of Conyza japonica. The structures of 1-4 were determined through spectroscopic analysis, while their absolute configurations were determined by comparison of calculated and experimental electronic circular dichroism (ECD) spectra. Conyterpenol D (4) was a new type of sesquiterpenoid with a seven-membered lactone ring. Compounds 1-23 were evaluated for their inhibitory activity against LPS-induced nitric oxide production in RAW264.7 macrophages and cytotoxicity against human hepatoma cell line (HepG2) and human breast adenocarcinoma cell line (MCF-7). Compounds 3, 4, and 12 displayed moderate inhibition against NO production with IC50 values in the range of 26.4-33.6 µM. And all compounds showed no obvious cytotoxicity against these two cancer cell lines at 100 µM.

Integrating Network Pharmacology and Experimental Validation to Investigate the Effects and Mechanism of Astragalus Flavonoids Against Hepatic Fibrosis.

Hepatic fibrosis (HF) represents the excessive wound healing where an excess amount of connective tissues is formed within the liver, finally resulting in cirrhosis or even hepatocellular carcinoma (HCC). Therefore, it is significant to discover the efficient agents and components to treat HF, thus restraining the further progression of hepatopathy. Astragalus membranaceus (Fisch.) Bunge [also called Astragali Radix (AR)] is a famous herb in traditional Chinese medicine (TCM), which possesses a variety of biological activities and exerts good therapeutic effects in the treatment of HF. Flavonoids account for the major active ingredients related to the AR pharmacological effects. Total AR flavonoids have been proved to exert inhibitory effects on hepatic fibrosis. This study aimed to further undertake network pharmacology analysis coupled with experimental validation and molecular docking to investigate the effects and mechanism of multiple flavonoid components from AR against liver fibrosis. The results of the network pharmacology analysis showed that the flavonoids from AR exerted their pharmacological effects against liver fibrosis by modulating multiple targets and pathways. The experimental validation data showed that the flavonoids from AR were able to suppress transforming growth factor beta 1 (TGF-ß1)-mediated activation of hepatic stellate cells (HSCs) and reduce extracellular matrix deposition in HSC-T6 cells via regulating the nuclear factor kappa B (NF-κB) signal transduction pathway. The results of the molecular docking study further showed that the flavonoids had a strong binding affinity for IκB kinase (IKKß) after docking into the crystal structure. The above results indicated that, flavonoids possibly exerted the anti-inflammatory effect on treating HF by mediating inflammatory signaling pathways. The potential mechanism of these flavonoids against liver fibrosis may be related to suppression of the NF-κB pathway through effective inhibition of IKKß. This study not only provides a scientific basis for clarifying the effects and mechanism of AR flavonoids against liver fibrosis but also suggests a novel promising therapeutic strategy for the treatment of liver fibrosis.

Salvia miltiorrhiza Restrains Reactive Oxygen Species-Associated Pulmonary Fibrosis via Targeting Nrf2-Nox4 Redox Balance.

Pulmonary fibrosis (PF) is characterized by myofibroblast activation, which can be triggered by oxidative stress. In this study, we investigated the antifibrotic effect of the ethyl acetate extract of Salvia miltiorrhiza (EASM) on PF and examined the underlying molecular mechanism. EASM suppressed myofibroblast activation with reduced extracellular matrix deposition in the lungs of mice subjected to bleomycin (BLM) challenge, demonstrating the inhibitory effects on PF. EASM positively alleviated oxidative stress by upregulating nuclear factor-erythroid 2-related factor 2 (Nrf2) and concomitantly downregulating NADPH oxidase 4 (Nox4) in the lungs of BLM-treated mice. This effect was also observed in an in vitro model of transforming growth factor beta 1 (TGF-ß1)-stimulated fibroblast activation. EASM reduced reactive oxygen species (ROS) generation in fibroblasts by stabilizing Nrf2 protein with promoting kelch-like ECH-associated protein 1 (Keap1) degradation. Nrf2 knockdown in the lungs of BLM-treated mice diminished the inhibitory effects of EASM on fibrosis, providing evidence in vivo to address the unique role of Nrf2. Additionally, EASM inhibited TGF-ß1/Smad3 signaling by downregulating protein kinase C delta (PKC-δ) and Smad3 phosphorylation (p-Smad3), which led to suppression of the TGF-ß1-induced fibrogenic response. These results indicate that EASM exhibits potent antifibrotic activity in vitro and in vivo, which might be associated with activation of Nrf2 pathway and inhibition of TGF-ß1/Smad3 pathway. Our findings support that EASM may act as an effective antifibrotic remedy for PF.