Furthermore, miR-27a overexpression promoted CCA cell proliferation, migration, and invasion, whereas knockdown of miR-27a suppressed cell proliferation, migration, and invasion. Taken together, these results suggest the potential usefulness of miR-27a in the prognosis and progression of CCA.We provide an update on how commonly prescribed osteoporosis therapies are being initiated in older adults in Ontario. Patients newly prescribed denosumab are older, more often female, and have more comorbidities than those prescribed bisphosphonates. Their characteristics, monitoring, and persistence with prescribed therapy differ from clinical trial participants. Real-world studies on oral bisphosphonates and denosumab might be valuable.

To provide a contemporary view on oral bisphosphonate and denosumab prescribing to older adults in routine care.

Using linked healthcare databases, we conducted a population-based cohort study of adults ≥ 66years newly prescribed oral bisphosphonates or denosumab between February 2013 and March 2017 in Ontario, Canada. We captured their clinical characteristics, monitoring, and continuous use of prescribed therapies. We illustrate how „real-world” new users of bisphosphonates and denosumab differ from randomized controlled trial (RCT) participants.

There were 107,847 iuct monographs, and drug reimbursement criteria. Given differences between real-world users and RCT participants, there may be a role for safety and effectiveness studies of bisphosphonates and denosumab in routine care.

The clinical characteristics and monitoring of new users of bisphosphonates and denosumab generally align with practice guidelines, product monographs, and drug reimbursement criteria. Given differences between real-world users and RCT participants, there may be a role for safety and effectiveness studies of bisphosphonates and denosumab in routine care.Chemotherapy-induced peripheral neuropathy (CIPN) manifests as mechanical allodynia and hyperalgesia, and is one of the main adverse effects of chemotherapeutic agents. Currently available therapeutic drugs are not sufficiently effective for the management of this adverse effect in the clinic. Therefore, the development of novel therapeutic agents for treating CIPN is necessary. Our previous study suggested the potential of aucubin and pedicularis-lactone (1) as active compounds responsible for the anti-allodynic property of Plantaginis Semen. However, the activity of purified 1 has not been evaluated due to its low content in Plantaginis Semen. In the present study, 1 was isolated from Viticis Fructus, as well as viteoid I (2) and viteoid II (3) during the process of isolation. The purities of isolated 1, 2, and 3 were determined as 67.15%, 92.12%, and 86.72%, respectively, by quantitative 1H-NMR, using DSS-d6 as an internal standard. Repeated daily oral administration of these three iridoids at a dose of 15 mg/kg significantly inhibited the PTX-induced mechanical allodynia in mice, suggesting the anti-allodynic activities of 1, 2, and 3. This study provides confirmatory evidence for the anti-allodynic activity of purified 1 and also reveals two additional active iridoids from Viticis Fructus. These three iridoids could be potential candidates for the treatment of CIPN.Peroxisome proliferator-activated receptors-γ (PPAR-γ), a ligand-activated transcription factor, activated by several ligands like fatty acids (linoleic acid being the most common) or their metabolites, can function as potential therapeutic target for various cancers. Although various synthetic ligands, thiazolidinediones (TZDs), serves as full agonist for PPAR-γ, application of these molecules has been discontinued due to adverse toxicity profile. Hence, with a dire need to identify novel PPAR-γ-agonists, the present in silico study aimed to determine the effectiveness of potent flavonoids, kaempferol (CID 5280863), quercetin (CID 5280343), and stilbenoid resveratrol (CID 445154) and their 806 derivatives towards PPAR-γ that could combat the deleterious effect of TZDs. The molecular docking experiment performed by FlexX elucidated the efficacy of derivatives; Kem204, Qur8, and Res183 of kaempferol, quercetin, and resveratrol respectively to be more effective against PPAR-γ as compared with other derivatives. The physicochemical and pharmacokinetic parameters of Kem204, Qur8, and Res183 follow the drug-likeness and thus comprise a pharmacologically active model to be considered for advancing further potential hits. Further molecular dynamics (MD) simulation study revealed the Qur8 compound to have favorable dynamic interactions within the PPAR-γ which certainly paves away in developing futuristic potential anticancer drugs. Graphical abstract.

Colon cancer cells can migrate and metastasize by undergoing epithelial-to-mesenchymal transition (EMT). Mesenchymal stem cells (MSCs) are non-cancerous, multipotent adult stem cells, which can also migrate. In this study, we wanted to compare the biological, physical, and functional properties of these migratory cells.

HT-29 and HCT-116, two human colon carcinoma cell lines, represent less aggressive and more aggressive cancer cells, respectively. MSCs were isolated from human bone marrow. After confirming the identity of all the cell types, they were evaluated for E-cadherin, β1-integrin, Vimentin, ZEB-1, β-catenin, and 18SrRNA using Q-PCR. MMP-2 and MMP-9 activity were evaluated using gelatin zymography. Functional tests like wound healing assay, migration assay, and invasion assay were also done. Biomechanical properties like cell stiffness and non-specific adhesion (between indenter probe and cell membrane) were evaluated through nanoindentation using atomic force microscopy (AFM).

Expression of EMT and stem cell markers showed typical expression patterns for HT-29, HCT-116, and MSCs. Functional tests showed that MSCs migrated faster than malignant cells. MMP-2 and MMP-9 activity reinforced this behavior. Interestingly, the migration/invasion capacity of MSCs was comparable to aggressive HCT-116, and more than HT-29. MSCs also showed the maximum cell stiffness and non-specific cell-probe adhesions, followed by HCT116 and HT29 cells.

Our findings indicate that the migratory properties of MSCs is comparable or even greater than that of cancer cells and despite their high migration potential, they also have the maximum stiffness.

Our findings indicate that the migratory properties of MSCs is comparable or even greater than that of cancer cells and despite their high migration potential, they also have the maximum stiffness.To develop a new antiviral preparation from a microbial source, the halophilic bacterium Bacillus pumilus E303035 was isolated from a soil sample collected at Qarhan Salt Lake in Qinghai, China. The inhibitory activity of an ethyl acetate extract of its fermentation broth was higher than that of an n-butanol extract. After isolation and purification, 9 compounds were obtained cyclo(L-Leu-L-Pro) (1), cyclo(L-Pro-L-Tyr) (2), Brevianamide F (3), 2-(3-Indolyl) ethanol (4), N-[2-(1H-indol-3-yl) ethyl] acetamide (5), 3, 3-di(1H-indol-3-yl)propane-1,2-diol (6), Lincomycin B (7), dibutylphthalate (8), and p-hydroxyphenethyl alcohol (9). Compounds 1, 5, and 9 showed inhibitory activities against potato virus Y (PVY). Compounds 1, 4, and 9 had significant inhibitory activity against genes HC-pro, P3, and Nib, compound 5 against gene P3, and compounds 1 and 4 against NIa. Compounds 1, 4, 5, and 9 had significant inhibitory activity against genes VPg and 6K1. Active compounds 1, 5, and 9 had various effects on the expression of viral genes related to pathogenesis. Expression of genes cullin and XTH was up-regulated and CP was down-regulated, compared to the positive control. In conclusion, compounds 1, 5, and 9 might be considered as potential antiviral agents for future development.Two environmentally friendly innovative extraction techniques – subcritical water (SWE) and microwave-assisted extraction (MAE) were applied for the extraction of phenolics from pomegranate peel. The impact of process conditions (SWE temperature 100-220 °C, extraction time 5-30 min; MAE solvent water and 50% ethanol, irradiation power 470 and 800 W) on the quality of extracts in terms of the content of total phenolics, total flavonoids, major phenolic constituents (gallic acid, ellagic acid, punicalin, punicalagin), as well as 5-hydroxymethylfurfural(HMF) amount was investigated. For SWE, temperature of 130 °C and 20 min extraction time were found optimal for obtaining high content of bioactive compounds and minimizing the yield of HMF. During MAE, phenolic compounds were effectively extracted by using lower microwave power and 50% ethanol. Comparing two techniques, MAE is more efficient than SWE for the extraction of phenolics from pomegranate peel while obtaining a HMF-free extracts.Cinnamomum cassia Presl. (CCP) is a popular natural spice possessing various pharmacological properties. We obtained polyphenol-rich fraction (CCP-P) from CCP by bioactivity-oriented purification method and evaluated its Wnt signaling inhibition activity. Firstly, the phenolic components were identified as the main bioactive compounds with anti-colorectal cancer activity. Then, we compared the anti-colorectal cancer activity of CCP extract obtained from different solvent by cell morphology alteration and EdU assay. Ethanol extract showed higher antiproliferative activity compared to water extract on HCT116 cells, with proliferating cells reducing to 41.12 and 21.83% at 156.00 μg GAE/mL, respectively. Next, separation and enrichment of polyphenols from ethanol extract was performed on AB-8 macroporous resins under optimal conditions. Further evaluation of the CCP-P bioactivity revealed that it exerted more potent antiproliferative activity on RKO and HCT116 cells, showing higher selectivity for Wnt-dependent colorectal cancer cells (CRCs). Ten major polyphenols were identified in the CCP-P by UPLC-ESI-MS/MS. In summary, this study presents evidence that CCP-derived polyphenols are promising potential candidates as functional food ingredients against CRC.

Heat sensitivity is a common contraindication in people with Multiple Sclerosis (pwMS), and physical fatigue is one of the most frequently reported symptoms that can affect quality of life. Increases in body temperature may exacerbate fatigue and heat-related symptoms. Decreasing body temperature via cooling devices may mitigate disease symptoms and improve physical abilities and quality of life. This study evaluates the effects of a cooling vest with sham condition on walking capacity using a commercially-available cooling vest specifically designed for pwMS.

A counter-balanced, cross-over design was used to assess the effects of a cooling vest (CryoVest Comfort, CryoInnov, France) (COLD) from a menthol-induced sham condition (CON) on ground walking time to exhaustion (T

, s) and distance at exhaustion (D

, m) in ambulatory pwMS. Secondary outcomes were heart rate (HR, bpm), thermal sensation (Tsens), skin chest (Tchest) and back (Tback) temperature.

Ten females with Multiple Sclerosis (59 ± 9years, EDSS 3.0-5.5) participated to the study. During COLD, pwMS walked significantly longer (1896 ± 602 vs. 1399 ± 404s, p < 0.001) and farther (1879 ± 539 vs. 1302 ± 318m, p < 0.001) than CON. Importantly, Tsens and HR at exhaustion were not significantly different between conditions, although Tchest (-2.7 ± 1.8°C, p < 0.01) and Tback (-3.9 ± 1.8°C, p < 0.001) were lower at volitional fatigue during COLD.

The lightweight cooling vest improved total walking time and distance in heat-sensitive pwMS. These physiological improvements were likely due to feeling perceptually cooler in the COLD trial, compared to the corresponding point of fatigue in the CON condition.

The lightweight cooling vest improved total walking time and distance in heat-sensitive pwMS. These physiological improvements were likely due to feeling perceptually cooler in the COLD trial, compared to the corresponding point of fatigue in the CON condition.