Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling.

OBJECTIVE: Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs; however, concerns regarding complexities and side effects persist, driving research for more effective, low-risk strategies. The promotion of white adipose tissue (WAT) browning has emerged as a promising approach. Moreover, alisol B 23-acetate (AB23A) has demonstrated efficacy in addressing metabolic disorders, suggesting its potential as a therapeutic agent in obesity management. Therefore, in this study, we aimed to investigate the therapeutic potential of AB23A for mitigating obesity by regulating metabolic phenotypes and lipid distribution in mice fed a high-fat diet (HFD). METHODS: An obesity mouse model was established by administration of an HFD. Glucose and insulin metabolism were assessed via glucose and insulin tolerance tests. Adipocyte size was determined using hematoxylin and eosin staining. The expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain reaction. Metabolic cage monitoring involved the assessment of various parameters, including food and water intake, energy metabolism, respiratory exchange rates, and physical activity. Moreover, oil red O staining was used to evaluate intracellular lipid accumulation. A bioinformatic analysis tool for identifying the molecular mechanisms of traditional Chinese medicine was used to examine AB23A targets and associated signaling pathways. RESULTS: AB23A administration significantly reduced the weight of obese mice, decreased the mass of inguinal WAT, epididymal WAT, and perirenal adipose tissue, improved glucose and insulin metabolism, and reduced adipocyte size. Moreover, treatment with AB23A promoted the expression of browning markers in WAT, enhanced overall energy metabolism in mice, and had no discernible effect on food intake, water consumption, or physical activity. In 3T3-L1 cells, AB23A inhibited lipid accumulation, and both AB23A and rapamycin inhibited the mammalian target of rapamycin-sterol regulatory element-binding protein-1 (mTOR-SREBP1) signaling pathway. Furthermore, 3-isobutyl-1-methylxanthine, dexamethasone and insulin, at concentrations of 0.25 mmol/L, 0.25 µmol/L and 1 µg/mL, respectively, induced activation of the mTOR-SREBP1 signaling pathway, which was further strengthened by an mTOR activator MHY1485. Notably, MHY1485 reversed the beneficial effects of AB23A in 3T3-L1 cells. CONCLUSION: AB23A promoted WAT browning by inhibiting the mTOR-SREBP1 signaling pathway, offering a potential strategy to prevent obesity. Please cite this article as: Han LL, Zhang X, Zhang H, Li T, Zhao YC, Tian MH, Sun FL, Feng B. Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling. J Integr Med. 2024; 22(1): 83-92.

Global prevalence of Plasmodium infection in wild birds: A systematic review and meta-analysis.

Avian malaria is a vector-borne parasitic disease caused by Plasmodium infection transmitted to birds by mosquitoes. The aim of this systematic review was to analyze the global prevalence of malaria and risk factors associated with infection in wild birds. A systematic search of the databases CNKI, WanFang, VIP, PubMed, and ScienceDirect was performed from database inception to 24 February 2023. The search identified 3181 retrieved articles, of which 52 articles met predetermined inclusion criteria. Meta-analysis was performed using the random-effects model. The estimated pooled global prevalence of Plasmodium infection in wild birds was 16%. Sub-group analysis showed that the highest prevalence was associated with adult birds, migrant birds, North America, tropical rainforest climate, birds captured by mist nets, detection of infection by microscopy, medium quality studies, and studies published after 2016. Our study highlights the need for more understanding of Plasmodium prevalence in wild birds and identifying risk factors associated with infection to inform future infection control measures.

Tiaoshen acupuncture for primary insomnia: a pilot randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effects of Tiaoshen (regulating the spirit) acupuncture on cognitive function and sleep quality in patients with primary insomnia (PI).@*METHODS@#Sixty patients with PI were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 2 cases dropped off, 1 case was excluded). The patients in the observation group were treated with acupuncture at Baihui (GV 20), Shenting (GV 24), Sishencong (EX-HN 1), and bilateral Benshen (GB 13), Shenmen (HT 7), Neiguan (PC 6), Sanyinjiao (SP 6). The patients in the control group were treated with shallow needling at non-effective points. Each treatment was provided for 30 min, once every other day, 3 treatments per week for 4 weeks. The Montreal cognitive assessment (MoCA), digit span test (DST), trail making test (TMT)-A, Pittsburgh sleep quality index (PSQI), and fatigue scale-14 (FS-14) were used to assess cognitive function and sleep quality before and after treatment, as well as in follow-up of 4-week after treatment completion. Correlation analysis was conducted between the differences in PSQI scores and differences in MoCA scores before and after treatment in the observation group.@*RESULTS@#Compared with before treatment, the total score, visuospatial and executive function score and delayed memory score of MoCA as well as DST backward score were increased (P<0.01), while TMT-A time, PSQI and FS-14 scores were significantly reduced (P<0.01) after treatment and in follow-up in the observation group. Compared with before treatment, the PSQI score in the control group was reduced (P<0.01, P<0.05). After treatment and in follow-up, the observation group had significantly higher total score, visuospatial and executive function score, delayed memory score of MoCA, and DST backward score compared to the control group (P<0.05, P<0.01). In the observation group, the TMT-A time was significantly shorter than that in the control group (P<0.05, P<0.01), and the PSQI and FS-14 scores were significantly lower than those in the control group (P<0.01). In the observation group, there was a negative correlation between the difference in PSQI scores (post-treatment minus pre-treatment) and the difference in MoCA scores (post-treatment minus pre-treatment) (r=-0.481, P<0.01). A similar negative correlation was found between the difference in PSQI scores (follow-up minus pre-treatment) and the difference in MoCA scores (follow-up minus pre-treatment) (r=-0.282, P<0.05).@*CONCLUSION@#Tiaoshen acupuncture could improve cognitive function, enhance sleep quality, and alleviate daytime fatigue in patients with PI. The improvement in cognitive function in patients with PI is correlated with the improvement in sleep quality.

Closure of skull base defects after endoscopic endonasal transsphenoidal surgery: the role of the local sphenoid mucosal flap for low flow leaks.

A local sphenoid mucosal flap (SMF) is naturally raised during endonasal exposure of the sella. Typically, these flaps are repositioned; however, they could be used in place of a nasoseptal flap (NSF) for closure of low-grade CSF leaks. In this study, we aim to establish the safety and efficacy of SMF closure for low-grade CSF leaks and to assess the impact on sinonasal quality of life (QoL) compared to NSF closure. In a consecutive, prospective cohort of anterior skull base pathology, data regarding sellar and suprasellar extension (Hardy grade), cavernous sinus invasion (Knosp grade), intraoperative (Kelly grade) and postoperative CSF leak, and sino-nasal QoL data (SNOT-22) were analysed. Of 187 patients with no/low flow (Kelly 0-1) intraoperative CSF leak, 127 (67.9%) received a SMF and 60 (32.1%) received a NSF. A total of 141/187 (75.4%) had no intraoperative leak, while 46/187 (24.6%) had grade-1 leaks. SMF were used in 70.9% (100/141) of cases without intraoperative leak, and 58.7% (27/46) of cases with Kelly grade-1 leaks. Hardy grade 4, grade E and Knosp grade 4 lesions were all more commonly closed with a NSF (p < 0.05). Two patients (1.1%) had postoperative CSF leaks, both in the SMF group, and both after no discernible intraoperative leak. Sinonasal QoL was below baseline for up to 3 months postoperatively. SMF cases tended to have better sinonasal QoL for up to 6 weeks after surgery. Thus, in the largest cohort to date, SMF are a safe alternative to NSF for closure low-grade skull base defects. Sinonasal QoL was better in the first 6 weeks after SMF closure than NSF closure.

Aerosolisation in endonasal endoscopic pituitary surgery.

PURPOSE: To determine the particle size, concentration, airborne duration and spread during endoscopic endonasal pituitary surgery in actual patients in a theatre setting. METHODS: This observational study recruited a convenience sample of three patients. Procedures were performed in a positive pressure operating room. Particle image velocimetry and spectrometry with air sampling were used for aerosol detection. RESULTS: Intubation and extubation generated small particles (< 5 µm) in mean concentrations 12 times greater than background noise (p < 0.001). The mean particle concentrations during endonasal access were 4.5 times greater than background (p = 0.01). Particles were typically large (> 75 µm), remained airborne for up to 10 s and travelled up to 1.1 m. Use of a microdebrider generated mean aerosol concentrations 18 times above baseline (p = 0.005). High-speed drilling did not produce aerosols greater than baseline. Pituitary tumour resection generated mean aerosol concentrations less than background (p = 0.18). Surgical drape removal generated small and large particles in mean concentrations 6.4 times greater than background (p < 0.001). CONCLUSION: Intubation and extubation generate large amounts of small particles that remain suspended in air for long durations and disperse through theatre. Endonasal access and pituitary tumour resection generate smaller concentrations of larger particles which are airborne for shorter periods and travel shorter distances.

Patient Wellbeing and Quality of Life After Nasoseptal Flap Closure for Endoscopic Skull Base Reconstruction.

BACKGROUND: The endoscopic endonasal approach to the skull base avoids some of the surgical morbidity associated with a transcranial approach, however it often results in large skull-base defects requiring secure closure. The nasoseptal flap has become the preferred method for closure of such defects but may be associated with its own morbidity. METHODS: A consecutive cohort of patients with skull base pathology with prospectively collected quality of life data using ASBQ and SNOT was analysed. They were grouped into those who received a nasoseptal flap and those who did not. Pre-operative total ASBQ and SNOT scores, and their individual components, were compared to data collected at days 1, 3, and 7; six-weeks; and 3, 6, and 12-months postoperatively. RESULTS: Of 158 patients available for analysis, nasoseptal flaps were performed in 52 (33%). Average follow-up (±standard deviation) was 8.1 ± 3.9 months for ASBQ data and 8.2 ± 3.8 months for SNOT data. In the first post-operative week, nasal symptoms and otalgia were worse in the flap group. At six-weeks and beyond, there was no difference between groups in overall ASBQ or SNOT scores, or in the rate of clinically-significant improvement in SNOT or ASBQ scores or their components. CONCLUSION: In the largest cohort of patients to date, the use of a nasoseptal flap is associated with nasal symptoms and otalgia in the acute post-operative period, but is not associated with any long-term detriment to quality of life after endoscopic skull base surgery.

Long noncoding RNA KCNQ1OT1 promotes apoptosis in neuroblastoma cells by regulating miR-296-5p/Bax axis.

Long noncoding RNAs (lncRNAs) are emerging as important regulators of multiple cellular processes such as cell invasion, growth, apoptosis and differentiation. LncRNAs can function as competing endogenous RNAs (ceRNAs) which sponge and sequester microRNA (miRNA) to regulate specific targets. Previously, we found that the target genes of several miRNAs, including FADD, Fas, Casp and Bax, are related to neuronal apoptosis and form a regulatory network. Among several factors, microRNA-296-5p expression was found to be negatively correlated with caspase activity and apoptosis. Here, we aimed to investigate the role of miR-296-5p in neuroblastoma (NB) cells. By performing quantitative real-time PCR (qRT-PCR), western blot and flow cytometry assays we analysed the expression of apoptotic markers in NB cells transfected with miR-296-5p mimics or inhibitor. Pathway-specific PCR array allowed us to identify the target genes of miR-296-5p. Using LncBase online tool, we predicted lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) as an upstream regulator of miR-296-5p. The binding of KCNQ1OT1 and miR-296-5p was validated via RNA immunoprecipitation and Biotin pull-down assays. We also demonstrate that miR-296-5p suppresses apoptosis of NB cells in vitro and in vivo. Mechanistically, miR-296-5p directly bound the 3'UTR of Bax mRNA, thus repressing Bax at the mRNA and protein level. Moreover, through bioinformatic analysis and molecular experiments, we showed that KCNQ1OT1 sponged miR-296-5p and impaired its effect on NB cell apoptosis. In summary, KCNQ1OT1 is a potent promoting factor of cell apoptosis, which acts by sponging miR-296-5p and upregulating Bax. Our findings identify a regulatory axis of cell fate in NB cells.

Homocysteine is Associated with Exaggerated Morning Blood Pressure Surge in Patients with Acute Ischemic Stroke.

BACKGROUND: Considerable researches suggest that high level of homocysteine (Hcy) is associated with the risk of ischemic stroke. Ambulatory blood pressure monitoring (ABPM) parameters have also been confirmed associated with cardio-cerebrovascular events. However, the relationship between Hcy and ABPM parameters remains unclear in patients with acute ischemic stroke. In this study, we aim to investigate the association between Hcy level and ABPM parameters in patients with acute ischemic stroke. METHODS: We enrolled 60 patients with acute ischemic stroke who received ABPM. We calculated ABPM parameters like morning blood pressure surge (MBPS), ambulatory arterial stiffness index, blood pressure variability, and night dipping patterns. RESULTS: Multivariate logistic regression analysis indicated that patients in the top quartile of Hcy level tended to have a higher level of prewaking and sleep-trough MBPS compared with patients in the lower 3 quartiles after adjusted for age and gender (P = .028 and P = .030, respectively). When treating Hcy as a continuous variable, the linear regression showed the association between Hcy level and both MBPS parameters remained significant (prewaking MBPS, r = .356, P = .022; sleep-trough MBPS, r = .365, P = .017, respectively). However, there is no association between Hcy level and ambulatory arterial stiffness index, blood pressure variability or night dipping patterns (P = .635, P = .348 and P = .127 respectively). CONCLUSIONS: There is a relationship between the 2 major cerebrovascular risk factors: MBPS and Hcy.

Hypoxia increases amyloid-ß level in exosomes by enhancing the interaction between CD147 and Hook1.

Hypoxia promotes the accumulation of amyloid-ß (Aß), which is related to the pathogenesis of Alzheimer's disease (AD). CD147 is considered as an additional subunit of γ-secretase regulated by hypoxia, and has been identified in exosomes. Aß is also found in exosomes that participate in the intercellular communication and amyloids propagation. This study was to investigate the role of CD147 in hypoxia-induced accumulation of Aß in exosomes. Our results showed that hypoxia increased the levels of Aß40 and Aß42 in exosomes and enhanced the interaction between CD147 and Hook1 in SH-SY5YAPP695 cells. Moreover, hypoxia increased the interaction between amyloid precursor protein (APP) and CD147 as well as the expression of CD147 in isolated membrane. After we interfered the interaction between CD147 and Hook1 by decreasing Rab22a expression, the hypoxia induced Aß accumulation in exosomes was significantly suppressed. In addition, the increased interaction between CD147 and Hook1 was further confirmed in hypoxia exposed C57BL/6 mice. Our findings reveal that hypoxia may increase exosome Aß level by enhancing the interaction between CD147 and Hook1.

Role of fungi in chronic rhinosinusitis through ITS sequencing.

OBJECTIVE: Next-generation sequencing increases the sensitivity of fungal identification and may improve our understanding of the role that fungi play in sinus health and disease, which remains incompletely understood. We sequenced the internal transcribed spacer (ITS) amplicon to explore the role of the mycobiome in chronic rhinosinusitis (CRS). METHODS: Swabs were collected intraoperatively from the middle meatus of 90 patients (63 with CRS; 27 controls). DNA was extracted, and ITS amplicon concentration was measured using fluorometry. Internal transcribed spacer amplicons were sequenced on the Illumina MiSeq (Illumina Inc San Diego CA). Sequencing data were analyzed using QIIME. RESULTS: Using conventional detection techniques of culture and histology, fungi only were identified in nine of 63 (14.3%) CRS patients (fungus-identified group); the remaining 54 CRS patients and all controls did not have fungus identified using the traditional techniques. This fungus-identified group had a significantly higher average ITS concentration and a significantly lower Shannon's diversity index compared to the other two groups. The most abundant organism sequenced was Aspergillus (35.22% of all sequences). Multivariate analysis showed that positive fungal detection using traditional techniques and computed tomography (CT) double densities were the most important clinical predictors of a high fungal biomass, whereas Lund-Mackay score, polyps, eosinophilia, and eosinophilic mucus were not significant in comparison. CONCLUSION: Fungal biomass estimated through ITS amplicon concentration correlated with traditional fungal detection techniques and CT double densities. Our results suggest that fungal dysbiosis only occurs in the sinuses of a selected subset of patients, and therefore could not be a universal determinant of sinus disease pathogenesis in all CRS patients. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:16-22, 2018.

Biofilm and Osteitis in Refractory Chronic Rhinosinusitis.

Our understanding of chronic rhinosinusitis (CRS) show biofilm and osteitis play a role in the disease's pathogenesis and refractory. Studies point to its role in pathogenesis and poor prognosis. Outside the research laboratory, biofilm detection remains difficult and specific treatment remains elusive. It is believed that osteitis is a nidus of inflammation and occurs more commonly in patients with refractory CRS. However, osteitis may be exacerbated by surgery and a marker of refractory disease, not a causative agent. Surgery remains the mainstay treatment for biofilm and osteitis with mechanical disruption and removal of disease load providing the most effective treatment.

The endoscopic transseptal approach for choanal atresia repair.

BACKGROUND: There are many standard repair options for choanal atresia including puncture, dilatation and drilling of the atretic plate. Most of these techniques involve postoperative stenting, which may promote granulation and scarring, with possible progression to restenosis. This article describes a novel approach for choanal atresia repair without postoperative stenting. METHODS: This article describes our experience with this choanal atresia repair technique utilized in 16 pediatric patients and 1 adult patient across multiple tertiary pediatric and rhinology centers during 2008 through 2015. Seven cases were bilateral and 10 were unilateral. Surgery was performed using an endoscopic transseptal approach with preservation of the mucosa and creation of flaps. No stents or packing was used. The main outcome measures were: response to treatment based on endoscopic examination, need for further revision and incidence of complications. RESULTS: All patients underwent routine postoperative endoscopic inspection of their nasal cavity, postnasal space, and assessment of neochoanal patency. The neochoanae of all patients remained patent to a minimum follow-up duration of 9 months with most patients follow up for 2 years or more. Two neonatal patients required transfusion postoperation from intraoperative bleeding. Two pediatric patients developed postoperative respiratory complications. One patient required revision surgery for nasal vestibule scarring from incision made on the nasal alar to facilitate the initial endoscopic approach. CONCLUSION: This novel endoscopic transseptal repair technique is effective in the management of choanal atresia. Careful fashioning of mucosal flaps and the omission of stenting has resulted in lasting patency of the neochoanae.

Transmastoid repair of superior semicircular canal dehiscence.

Objective/Hypothesis Superior semicircular canal (Sup SC) dehiscence syndrome is a rare condition, causing a variety of auditory and vestibular symptoms. The traditional surgical management is a middle cranial fossa, extradural approach to resurface the Sup SC. Recently, a transmastoid approach for plugging of the Sup SC has been developed. We present further data supporting the use of the transmastoid approach in preference to the middle fossa approach. Design This is a retrospective multi-institutional case series. Method We included 10 patients in this case series from two tertiary otology institutions. Sup SC dehiscence was confirmed by correlation of clinical symptoms with positive audiometric, vestibular evoked myogenic potential, and computed tomography findings. A transmastoid approach was used for plugging of the Sup SC. Either a single fenestration was created at the site of dehiscence or separate fenestrations sited ampullopetal and ampullofugal to the dehiscence. Results All patients who underwent this procedure had good symptom control and hearing preservation postoperatively. Conclusion In patients with adequate temporal bone pneumatization, the transmastoid approach provides a safe and effective alternative to the middle cranial fossa approach. This series has demonstrated excellent symptom control and preservation of hearing with the transmastoid approach.

Improving temporal bone dissection using self-directed virtual reality simulation: results of a randomized blinded control trial.

OBJECTIVE: A significant benefit of virtual reality (VR) simulation is the ability to provide self-direct learning for trainees. This study aims to determine whether there are any differences in performance of cadaver temporal bone dissections between novices who received traditional teaching methods and those who received unsupervised self-directed learning in a VR temporal bone simulator. STUDY DESIGN: Randomized blinded control trial. SETTING: Royal Victorian Eye and Ear Hospital. SUBJECTS: Twenty novice trainees. METHODS: After receiving an hour lecture, participants were randomized into 2 groups to receive an additional 2 hours of training via traditional teaching methods or self-directed learning using a VR simulator with automated guidance. The simulation environment presented participants with structured training tasks, which were accompanied by real-time computer-generated feedback as well as real operative videos and photos. After the training, trainees were asked to perform a cortical mastoidectomy on a cadaveric temporal bone. The dissection was videotaped and assessed by 3 otologists blinded to participants' teaching group. RESULTS: The overall performance scores of the simulator-based training group were significantly higher than those of the traditional training group (67% vs 29%; P < .001), with an intraclass correlation coefficient of 0.93, indicating excellent interrater reliability. Using other assessments of performance, such as injury size, the VR simulator-based training group also performed better than the traditional group. CONCLUSIONS: This study indicates that self-directed learning on VR simulators can be used to improve performance on cadaver dissection in novice trainees compared with traditional teaching methods alone.

Peptidomimetics in the discovery of new insect growth regulators: studies on the structure-activity relationships of the core pentapeptide region of allatostatins.

Cockroach-type allatostatins (ASTs) were discovered in cockroaches through their capacity to inhibit the production of juvenile hormone by the corpora allata (CA). ASTs were considered as potential insect growth regulator (IGR) candidates, but several disadvantages, including the absence of the effect in vivo and rapid degradation in vivo, precluded their application in pest management. The CA were selected as the target, and the core pentapeptide region (YDFGL) was chosen as the lead sequence in the search for new IGRs based on the allatostatins. We designed and synthesized 24 analogues, which mimicked each amino acid of the core region, to determine structure-activity relationships and the possibility of shortening the ASTs in the core region while retaining activity. The results suggest that the sequence FGLa is more important than Y/FX because Y/FX mimics show strong effects in vitro and in vivo. In particular, compound I3 was synthesized by substitution of Y/FX with 6-phenylhexnoic acid and exhibits higher activity in vitro than the complete core region. Furthermore, compound I3 has a clear effect in vivo on juvenile hormone (JH) biosynthesis of Diploptera punctata females, providing a possible application for cockroach management. On the basis of the structure-activity relationship of pentapeptide analogues, a general structure of potential potent AST analogues is proposed here. A new approach using peptidomimetics in the discovery of IGRs is demonstrated in our study.

Synthesis, biological activity, and hologram quantitative structure-activity relationships of novel allatostatin analogues.

Cockroach-type allatostatins (FGLamides) (ASTs) can inhibit the production of juvenile hormone in vitro, and they therefore are regarded as possible insect growth regulator (IGR) candidates for pest control. However, several shortcomings, such as the absence of in vivo effects, rapid degradation, and high production costs, preclude their practical use in pest management. To discover new IGRs, 25 novel analogues of pentapeptide (Y/FXFGLa) were designed and synthesized with different aromatic acids, fatty acids, and dicarboxylic acids as the Y/FX region replacements on the basis of previous results. Their bioactivities in vitro were determined, and the results showed that eight analogues (K14, K15, K17, K18, K19, K23, K24, and K25) were more active than the lead, core region pentapeptide. The IC(50) values of K15 and K24 (IC(50) = 1.79 and 5.32 nM, respectively) were even lower than that of the natural AST, Dippu-AST 1(IC(50) = 8 nM), which indicated both analogues have better activity than Dippu-AST 1; particularly, K15 has better activity than most natural Dippu-ASTs. A predictable and statistically meaningful hologram quantitative structure-activity relationship (HQSAR) model of 32 AST analogues (28 as training sets and 4 as test sets) was obtained. The final model suggested that a potent AST analogue should contain an aromatic group, a linker of appropriate length, and the FGLa portion. These results will be useful in the design of new AST analogues that are structurally related to the training set compounds.

Randomised double-blind, placebo-controlled trial of coenzyme Q, therapy in class II and III systolic heart failure.

BACKGROUND: Coenzyme Q10 (CoQ10) supplementation has been reported to improve symptoms of heart failure and quality of life, and to reduce hospitalisation. Most prior trials have been open-label and in some, only 50% of patients took angiotensin converting enzyme inhibitors (ACEI). AIM: To determine the effects of CoQ10 in patients with a New York Heart Association (NYHA) Class II or III heart failure due to ischaemic or dilated cardiomyopathy who have been treated with ACEI but not beta-blockers. METHODS: Thirty-nine patients in NYHA Class II or III heart failure were randomised in ad ouble-blind, placebo-controlled study with 150 mg/day of oral CoQ10 or placebo. RESULTS: Thirty-five patients completed the trial. After 3 months of therapy, the NYHA class in the CoQ10 group (n = 17) showed a significant improvement of 0.5 class compared with the placebo (n = 18) (P = 0.01). Specific Activities Scale class showed a significant (P = 0.004) improvement in the CoQ10 group, but no change in the placebo group. The C-min walk-test distance showed a significant (P = 0.047) increase in the CoQ10 group with no change in the placebo group (between-group difference P = 0.29). For the Naughton exercise test times the difference in increase in exercise time approached significance in favour of the CoQ10 group (P = 0.056). There was a correlation between the increase in exercise time and the increase in serum CoQ10 level (P = 0.024). There was a threefold increase in the CoQ10 level in the treated group (0.7 +/- 0.4 to 2.1+/- 0.3 microg/mL), but no change in the placebo group. CONCLUSIONS: This pilot study accords with published data suggesting that CoQ10 therapy improves cardiac functional status in patients with moderately severe dilated cardiomyopathy receiving maximal non beta-blocker therapy. Future multicentre studies with larger numbers are indicated.

Expression of activin receptors, follistatin and betaglycan by human endometrial stromal cells; consistent with a role for activins during decidualization.

Decidualization of the human endometrium is critical for implantation, but the mechanisms involved are largely unknown. Activin subunits are expressed in endometrium during decidualization. From its known actions in cell differentiation and tissue remodelling, we hypothesized that activin A is involved in the paracrine regulation of decidualization. We examined the expression of activin receptors (ActRs) by semi-quantitative and real-time RT-PCR. mRNA for all ActR subtypes (Ia, Ib, IIa and IIb) was detected in endometrium, with maximal expression in the early secretory phase and in early pregnancy. ActR protein was localized exclusively to stromal and endothelial cells. This expression pattern was confirmed by in-situ hybridization. Activin bioavailability is locally regulated by its binding protein, follistatin, and also by the antagonist, inhibin. Inhibin competition for ActRII binding is enhanced by the binding protein, betaglycan. Follistatin and betaglycan were also detected in the endometrium, localized to stromal and epithelial cells. This co-expression of activin subunits, receptors and binding proteins indicates that stromal cells are capable of responding to activin, and that there is tight local regulation of activin action within the endometrium. As activin production is up-regulated in decidual cells, this provides further evidence for an involvement of activins during stromal cell decidualization.