Explore the vast range of titles available.

Mobility disability (MD) refers to substantial limitations in life activities that arise because of movement impairments. Although MD is most prevalent in older individuals, it can also affect younger adults. Increasing evidence suggests that inflammation can drive the development of MD and may need to be targeted for MD prevention. Physical exercise has anti-inflammatory properties and has been associated with MD prevention. However, no studies to date have examined whether exercise interventions affect the peripheral inflammatory status in younger adults with MD. To this end, we used blood samples from young and middle-aged adults with MD (N = 38; median age = 34 years) who participated in a 12-week intervention that included aerobic and resistance exercise training. A pre-post assessment of inflammatory biomarkers was conducted in plasma from two timepoints, i.e., before the exercise trial and at follow-up (3–7 days after the last exercise session). We successfully measured 15 inflammatory biomarkers and found that exercise was associated with a significant reduction in levels of soluble fractalkine, transforming growth factor beta 1 (TGF-β1), eotaxin-1 and interleukin (IL) 6 (corrected α = 0.004). We also found significant male-specific effects of exercise on (i) increasing IL-16 and (ii) decreasing vascular endothelial growth factor-A (VEGF-A). In line with our results, previous studies have also found that exercise can reduce levels of TGF-β1, eotaxin-1 and IL-6. However, our finding that exercise reduces plasma levels of fractalkine in younger adults with MD, as well as the sex-dependent findings, have not been previously reported and warrant replication in larger cohorts. Given the suggested role of inflammation in promoting MD development, our study provides additional support for the use of physical exercise as a treatment modality for MD.

Background: Eribulin mesylate (eribulin) is a first-in-class halichondrin B-based microtubule dynamics inhibitor. To compare the anti-angiogenic activity of eribulin to that of bevacizumab, we compared tumour vessel remodelling and reoxygenation between the two agents. Methods: Patients with advanced breast cancer with stage III/IV were eligible for the study. Patients were assigned to receive either eribulin or single-agent bevacizumab. Tissue concentrations of oxyhaemoglobin (O 2 Hb) and deoxyhaemoglobin (HHb), and oxygen saturation (SO 2 ) of breast tumours before and day 7 after the first infusion were repeatedly measured using diffuse optical spectroscopic imaging (DOSI). A pair of blood samples was collected for multiplex biomarker studies. Results: Baseline DOSI measurement of all 29 patients (eribulin, n =14 and bevacizumab, n =15) revealed significantly higher tumour concentrations of O 2 Hb and HHb than that in the normal breast tissue. After eribulin treatment, DOSI revealed a significant decrease in HHb concentration and increased SO 2 during the observation period. This trend was not observed for bevacizumab. Instead, bevacizumab significantly decreased the concentration of O 2 Hb. The multiplex biomarker study revealed that both eribulin and bevacizumab decreased plasma concentrations of VEGF and bFGF, but only eribulin treatment suppressed the plasma concentration of TGF- β 1. Conclusions: Eribulin, but not bevacizumab, treatment increased tumour SO 2 . Suppression of TGF- β 1 by eribulin could have a favourable anti-angiogenic effect. Our results suggest that differences in vascular remodelling between these two agents may account for their different effects on tumour reoxygenation.

Diabetic kidney disease (DKD) is a debilitating complication of diabetes, which develops in 40% of the diabetic population and is responsible for up to 50% of end-stage renal disease (ESRD). Tocotrienols have shown to be a potent antioxidant, anti-inflammatory, and antifibrotic agent in animal and clinical studies. This study evaluated the effects of 400 mg tocotrienol-rich vitamin E supplementation daily on 59 DKD patients over a 12-month period. Patients with stage 3 chronic kidney disease (CKD) or positive urine microalbuminuria (urine to albumin creatinine ratio; UACR > 20–200 mg/mmol) were recruited into a randomized, double-blind, placebo-controlled trial. Patients were randomized into either intervention group (n = 31) which received tocotrienol-rich vitamin E (Tocovid SupraBioTM; Hovid Berhad, Ipoh, Malaysia) 400 mg daily or a placebo group which received placebo capsules (n = 28) for 12 months. HbA1c, renal parameters (i.e., serum creatinine, eGFR, and UACR), and serum biomarkers were collected at intervals of two months. Tocovid supplementation significantly reduced serum creatinine levels (MD: −4.28 ± 14.92 vs. 9.18 ± 24.96), p = 0.029, and significantly improved eGFR (MD: 1.90 ± 5.76 vs. −3.29 ± 9.24), p = 0.011 after eight months. Subgroup analysis of 37 patients with stage 3 CKD demonstrated persistent renoprotective effects over 12 months; Tocovid improved eGFR (MD: 4.83 ± 6.78 vs. −1.45 ± 9.18), p = 0.022 and serum creatinine (MD: −7.85(20.75) vs. 0.84(26.03), p = 0.042) but not UACR. After six months post washout, there was no improvement in serum creatinine and eGFR. There were no significant changes in the serum biomarkers, TGF-β1 and VEGF-A. Our findings verified the results from the pilot phase study where tocotrienol-rich vitamin E supplementation at two and three months improved kidney function as assessed by serum creatinine and eGFR but not UACR.

Objective: Obesity is associated with an exacerbated metabolic condition that is mediated through impairing balance in the secretion of some adipo-myokines. Therefore, the objective of the present study was to explore the impact of astaxanthin supplementation in conjunction with a 12-week CrossFit training regimen on some selected adipo-myokines, insulin insensitivity, and serum lipid levels in obese males. Material and Methods: This study is a randomized control trial design; 60 obese males were randomly divided into four groups of 15, including the control group (CG), supplement group (SG), training group (TG), and combined training and supplement group (TSG). The participants were subjected to 12 weeks of astaxanthin (AST) supplementation [20 mg/d capsule, once/d] or CrossFit training or a combination of both interventions. The training regimen comprised 36 sessions of CrossFit, each lasting 60 min, conducted three times per week. The metabolic indices, body composition, anthropometrical, cardio-respiratory, and also some plasma adipo-myokine factors, including decorin (DCN), activin A, myostatin (MST), transforming growth factor (TGF)-β1, and follistatin (FST), were examined 12 and 72 h before the initiation of the main interventional protocols, and then 72 h after the final session of the training protocol. Results: There was no significant difference in the baseline data between the groups (p > 0.05). There were significant interactions between group x time for DCN (η2 = 0.82), activin A (η2 = 0.50), FST (η2 = 0.92), MST (η2 = 0.75), and TGFB-1 (η2 = 0.67) (p < 0.001 for all the variables). Significantly changes showed for DCN in TSG compared to TG and SG and also TG compared to SG (p = 0.0001); for activin A in SG compared to TG (p = 0.01) and TSG (p = 0.002); for FST in SG compared to TG and TSG (p = 0.0001), also in TSG compared to TG (p = 0.0001); for MST in SG, TG, and TSG compared to CG (p = 0.0001) and also in TSG compared to SG (p = 0.0001) and TG (p = 0.001); for TGFB-1 in SG, TG, and TSG compared to CG (p = 0.0001) and also TSG compared to SG (p = 0.0001) and TG (p = 0.001). Conclusions: The 12-week CrossFit training concurrent with AST supplementation reduced anthropometric and metabolic factors and also serum lipid levels while producing positive changes in body composition and cardiovascular factors. Increased FST and DCN and reduced activin A, MST, and TGF-β1 were other affirmative responses to both interventions.

Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFβ-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.

This study aimed to assess the potential antifibrotic impact of zinc sulfate in chronic Hepatitis C Virus (HCV) patients receiving direct-acting antiviral therapy. This randomized controlled study included 50 chronic HCV-infected patients with fibrosis stage (F1 & F2). Participants were randomly assigned to two groups: Group 1 (Control group, n = 25) received standard direct-acting antiviral therapy for 3 months, while Group 2 (Zinc group, n = 25) received 50 mg/day of zinc sulfate in addition to the standard direct-acting antiviral therapy for the same duration. Baseline and 3-month post-intervention assessments included evaluating serum levels of hyaluronic acid, transforming growth factor beta-1, and fibronectin. Furthermore, indices of liver fibrosis, such as the Fibrosis Index based on the 4 factors (FIB-4) and the Aspartate Transaminase-to-Platelet-Ratio Index (APRI), were calculated during these assessments. At baseline, the two studied groups had no statistical difference in demographic and laboratory data. After treatment, serum zinc levels significantly increased in the zinc-treated group compared to the control group. Additionally, serum fibronectin and hyaluronic acid levels were significantly reduced in group 2 (zinc group) compared to group 1 (control group). Moreover, zinc group showed lower APRI scores than the control group after a 3-month follow-up period, but there was non-significant difference in FIB-4 scores between the two groups after treatment. Furthermore, total bilirubin levels were reduced after zinc therapy for 3 months. Administering zinc sulfate could potentially serve as a safe and efficient therapeutic strategy for the management of hepatic fibrosis in individuals with chronic hepatitis C virus. ClinicalTrials.gov identifier: NCT05465434, On 19/7/2022.

Hepatic fibrosis is the net accumulation of matrix tissue components which controlled by pro-fibrolytic enzymes, matrix metalloproteinases (MMPs), and pro-fibrotic cytokine, TGF-β 1 , and enzymes, tissue inhibitors of MMPs (TIMPs). Vitamin D (VD) supplementation has been shown to reverse these processes in vitro and in vivo . This study sought to determine the effect of VD supplementation on serum fibrotic markers in chronic hepatitis C (CHC) patients. Fifty-four CHC patients with VD deficiency were randomized into two groups, a VD group (n = 29) and a placebo group (n = 29). The serum levels of 25-hydroxy VD, TGF-β 1 , TIMP-1, MMP2 and MMP9 were measured at baseline and at the end of the 6-week study period. Upon correction of VD levels, TGF-β 1 and TIMP-1 levels were decreased, and the MMP2 and MMP9 levels were significantly increased in the VD group. A comparison of the mean changes (delta) in the markers between groups showed that TGF-β 1 and TIMP-1 levels were significantly decreased and the MMP2 and MMP9 were significantly higher in the VD group than in the placebo group. By using CHC patients as a model, this study provides additional evidence that VD plays an important role in the reversal of hepatic fibrogenesis.

The study aims to evaluate the efficacy and safety of two Chinese herbal formulae for the treatment of stable COPD. A multicenter, double-blind, double-dummy, and randomized controlled trial (RCT) was conducted. All groups were treated with additional conventional medicines. There were a 6-month treatment and a 12-month follow-up for 5 times. Primary outcomes included lung function test, exacerbation frequency, score of SGRQ. Second outcomes consisted of 6MWD, BODE index, psychological field score, inflammatory factors and cortisol. A total of 331 patients were randomly divided into two active treatment groups (Bushen Yiqi (BY) granule group, n = 109; Bushen Fangchuan (BF) tablet group, n = 109) and a placebo group (n = 113). Finally 262 patients completed the study. BY granule & BF tablet increased the values of VC, FEV1 (%) and FEV1/FVC (%), compared with placebo. BY granule improved PEF. Both treatments reduced acute exacerbation frequency (P = 0.067), BODE index and psychological field score, while improved 6MWD. In terms of descent rang of SGRQ score, both treatments increased (P = 0.01). Both treatments decreased inflammatory cytokines, such as IL-8, and IL-17(P = 0.0219). BY granule obviously descended IL-17(P<0.05), IL-1β (P = 0.05), IL-6, compared with placebo. They improved the level of IL-10 and cortisol. BY granule raised cortisol (P = 0.07) and decreased TNF-α. Both treatments slightly descended TGF-β1. In terms of safety, subject compliance and drug combination, there were no differences (P>0.05) among three groups. BY granule and BF tablet were positively effective for the treatment of COPD, and the former performed better in general. Chinese Clinical Trial Register center ChiCTR-TRC-09000530.

Background Non-alcoholic fatty liver disease is a common health problem associated with increased liver and vascular specific complications. Aim The purpose of this study was to assess and compare the effect of fenofibrate alone or in combination with pentoxifylline on the measured biochemical parameters, inflammatory pathway and liver stiffness in patients with non-alcoholic fatty liver disease. Methods The study design was randomized controlled trial. From July 2013 to June 2014, we recruited 90 non-alcoholic fatty liver patients from the Internal Medicine Department at Tanta University Hospital, Egypt. They were classified randomly into two groups to receive fenofibrate 300 mg daily or fenofibrate 300 mg daily plus pentoxifylline 1200 mg/day in three divided doses for 24 weeks. Fasting blood sample was obtained before and 24 weeks after treatment for biochemical analysis of liver and lipid panels, tumor necrosis factor-alpha, hyaluronic acid, transforming growth factor beta 1, fasting plasma insulin and fasting glucose. Liver stiffness measurement was carried out using fibro-scan. Data were statistically analyzed by paired and unpaired Student’s t test. Results The data obtained suggests that adding pentoxifylline to fenofibrate does not provide a beneficial effect on lipid panel, but has a beneficial effect on indirect biochemical markers of hepatic fibrosis, a direct marker linked to matrix deposition (hyaluronic acid), a cytokine/growth factor linked to liver fibrosis (transforming growth factor beta 1), the inflammatory pathway, insulin resistance and liver stiffness as compared to fenofibrate alone. Conclusion The combination pentoxifylline plus fenofibrate may represent a new therapeutic strategy for non-alcoholic fatty liver disease as it resulted in more beneficial effects on direct and indirect markers of liver fibrosis, liver stiffness, insulin resistance and inflammatory pathway implicated in NAFLD.

Background:Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT).Methods:Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor–β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect.Results:After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different.Conclusions:We provide evidence—decreased concomitant heroin use—of low-dose add-on DM’s efficacy for treating opioid-dependent patients undergoing MMT.