Cervical spondylotic myelopathy (CSM) is a common cause of disability with few treatments. Aberrant mitochondrial dynamics play a crucial role in the pathogenesis of various neurodegenerative ...diseases. Thus, regulation of mitochondrial dynamics may offer therapeutic benefit for the treatment of CSM. Muscone, the active ingredient of an odoriferous animal product, exhibits anti‐inflammatory and neuroprotective effects for which the underlying mechanisms remain obscure. We hypothesized that muscone might ameliorate inflammatory responses and neuronal damage by regulating mitochondrial dynamics. To this end, the effects of muscone on a rat model of chronic cervical cord compression, as well as activated BV2 cells and injured neurons, were assessed. The results showed that muscone intervention improved motor function compared with vehicle‐treated rats. Indeed, muscone attenuated pro‐inflammatory cytokine expression, neuronal‐apoptosis indicators in the lesion area, and activation of the nod‐like receptor family pyrin domain‐containing 3 inflammasome, nuclear transcription factor‐κB, and dynamin‐related protein 1 in Iba1‐ and βIII‐tubulin‐labeled cells. Compared with vehicle‐treated rats, compression sites of muscone‐treated animals exhibited elongated mitochondrial morphologies in individual cell types and reduced reactive oxygen species. In vitro results indicated that muscone suppressed microglial activation and neuronal damage by regulating related‐inflammatory or apoptotic molecules. Moreover, muscone inhibited dynamin‐related protein 1 activation in activated BV2 cells and injured neurons, whereby it rescued mitochondrial fragmentation and reactive oxygen species production, which regulate a wide range of inflammatory and apoptotic molecules. Our findings reveal that muscone attenuates neuroinflammation and neuronal damage in rats with chronic cervical cord compression by regulating mitochondrial fission events, suggesting its promise for CSM therapy.
Cervical spondylotic myelopathy (CSM) is a common cause of disability with few treatments. Muscone, the ingredient from an animal product, exhibits anti‐inflammatory and neuroprotective effects for which the underlying mechanisms remain obscure. In this study, we explored the effects of muscone on a classic CSM rat model, microglial and neuronal cell. Results indicated that muscone could attenuate both inflammatory responses and neuronal damage in a rat CSM model and in vitro. Such effects may be associated with its role on mitochondrial dynamics and downstream signaling, suggesting that mitochondrial dynamics and muscone may be new highlights for the treatment of CSM.
Intraarticular hyaluronan or platelet-rich plasma (PRP) is widely used in the treatment of knee osteoarthritis (OA). The efficacy of combined hyaluronan with PRP remained inconclusive. This study ...aimed to investigate the efficacy of combined a single crosslinked hyaluronan (HYAJOINT Plus) and a single PRP versus a single PRP in patients with knee OA. In a prospective randomized-controlled trial, 85 patients with knee OA (Kellgren-Lawrence 2) were randomized to receive a single intraarticular injection of HYAJOINT Plus (3 ml, 20 mg/ml) followed by 3 ml PRP (the combined-injection group, N = 43) or a single injection of 3 ml PRP (the one-injection group, N = 42). The primary outcome was the change from baseline in the visual analog scale (VAS) pain (0-00 mm) at 6 months. Secondary outcomes included The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, Likert Scale), Lequesne index, single leg stance test (SLS), use of rescue analgesics and patient satisfaction at 1, 3 and 6 months. Seventy-eight patients were available for the intention-to-treat analysis at 6 months. Both groups improved significantly in VAS pain, WOMAC, Lequesne index and SLS at each follow-up visit (p < 0.001). Patients receiving a single PRP experienced significantly greater improvements in VAS pain than patients receiving combined injections at 1-month follow-up (adjusted mean difference: - 5.6; p = 0.017). There were no significant between-group differences in several of the second outcomes at each follow-up visit, except the WOMAC-pain and WOMAC-stiffness scores favoring the one-injection group at 1 month (p = 0.025 and p = 0.011). However, at 6-month follow-up, the combined-injection group achieved significantly better VAS pain reduction (p = 0.020). No serious adverse events occurred following injections. In conclusion, either combined injections of HYAJOINT Plus and PRP or a single PRP alone was safe and effective for 6 months in patients with Kellgren-Lawrence 2 knee OA. Combined injections of HYAJOINT Plus and PRP achieved better VAS pain reduction than a single PRP at 6 months. The results indicating a long term benefit effect of a combination of HYAJOINT Plus and PRP in a particular subset of patients with moderate knee OA need to be replicated in larger trials.ClinicalTrials.gov number NCT04315103.
Research has shown that long noncoding RNAs (lncRNAs) play significant roles in colorectal cancer (CRC). However, the role of lnc‑UCID (lncRNA upregulating CDK6 by interacting with DHX9) in CRC ...remains largely unknown. In the present study, analyses revealed that lnc‑UCID was markedly upregulated in CRC compared with that in normal specimens. Functional experiments showed that the depletion of lnc‑UCID inhibited CRC cell invasion and migration significantly, while overexpression of lnc‑UCID had the opposite effect. A candidate target of lnc‑UCID, microRNA miR‑152‑3p, was identified using bioinformatic analysis. Moreover, in CRC tissue, we noted an inverse correlation between miR‑152‑3p and lnc‑UCID expression levels. Overexpression and knockdown experiments revealed opposing roles for miR‑152‑3p and lnc‑UCID, suggesting that lnc‑UCID negatively regulates miR‑152‑3p. Luciferase reporter assays demonstrated that miR‑152‑3p directly targets lnc‑UCID. The results suggest that lnc‑UCID acts as an endogenous miRNA sponge, competing for miR‑152‑3p binding and thereby regulating the miRNA's targets. Overall, we propose that the lnc‑UCID/miR‑152‑3p/Wnt/β‑catenin signaling axis represents a novel mechanism that explains the migration and invasion of CRC.
Abstract
Background
Intraarticular plasma-rich platelet (PRP) and hyaluronic acid (HA) have each been shown to be effective for treating knee osteoarthritis (OA). Evidence supporting the combination ...therapy is controversial. This study aimed to investigate the efficacy of a single intraarticular PRP injection combined with different HAs in patients with knee OA.
Methods
In this prospective randomized-controlled trial, 99 patients with Kellgren-Lawrence grade 2 knee OA with average knee pain ≥ 30 mm on a 0-100 mm pain visual analog scale (VAS) were randomized into two groups. The PRP + Artz group received a single intraarticular HA (Artz, 2.5 ml, 10 mg/ml) followed by 3 ml PRP (
n
= 50). The PRP + HYAJOINT Plus group received a single intraarticular cross-linked HA (HYAJOINT Plus, 3 ml, 20 mg/ml) followed by 3 ml PRP (
n
= 49). All patients were evaluated before and at 1, 3 and 6 months after injections. The primary outcome was the VAS pain reduction from baseline at 6 months. Secondary outcome measures included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne index, single leg stance (SLS) test and patient satisfaction.
Results
Ninety-five patients were analyzed by intention-to-treat analysis. Both groups improved significantly in VAS pain, WOMAC, Lequesne index and SLS at 1, 3 and 6 months post intervention (
p
< 0.05). Between-group comparisons showed no significant differences at most follow-up time points, except better improvements in Lequesne index at 1 month (
p
= 0.003) and WOMAC-stiffness score at 6 months (
p
= 0.020) in the PRP + Artz group, and superiority in SLS at 1, 3 and 6 months in the PRP+ HYAJOINT Plus group (
p
< 0.001,
p
= 0.003 and
p
= 0.004). Additional Johnson-Neyman analyses showed that among the patients with baseline WOMAC-pain score > 8.5, WOMAC-function score > 21.7 and WOMAC-total score > 32.0, respectively, those treated with PRP + HYAJOINT Plus injections had better effects in WOMAC-pain, WOMAC-function and WOMAC-total scores than those treated with PRP + Artz at 3 months postinjection (
p
< 0.05). Both groups reported high satisfaction. No serious adverse events occurred during the study.
Conclusions
A single PRP injection combined with Artz or HYAJOINT Plus is effective and safe for 6 months in patients with knee OA. Both injection regimens are potential treatment options for knee OA. Further studies are needed to confirm these results.
Trial registration
The study was registered at ClinicalTrials.gov (NCT04931719), retrospectively. Date of registration 18/6/2021.
Name of trial registry
Comparing efficacy of single PRP combined with different hyaluronans for knee osteoarthritis.
Level of evidence
Therapeutic Level 1.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDT is a well-established therapeutic modality for many types of cancer. Photoluminescent cyclometalated iridium(III) complexes are one of the most commonly used classes of organometallic compounds ...with potential beneficial applications in bioimaging and as promising anticancer agents. In the present study, three new cyclometalated iridium(III) complexes (Ir1–Ir3) containing guanidinium ligands were found to exert excellent cytotoxic effects on different types of cancer cells upon light irradiation at 425 nm. Notably, Ir1 conferred almost no dark toxicity (IC50 > 100 μM) to HepG2 cells, but the value decreased by 387-fold to 0.36 μM following 10 min of light irradiation (425 nm). Further mechanistic investigation revealed that complex Ir1 could induce apoptosis via the activation of reactive oxygen species (ROS)-mediated mitochondrial signaling pathways in the presence or absence of light irradiation. In vivo studies demonstrated that Ir1 significantly inhibited tumor growth in HepG2 xenograft-bearing mice under light irradiation at 425 nm. Taken together, these findings indicate that designing PDT-based Ir(III) complexes may hold a great deal of promise for anticancer drug development.
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•Three Ir(III) complexes containing guanidinium ligands were synthesized.•Ir1 displayed higher phototoxicities to HepG2 cells upon irradiation at 425 nm.•Ir1 mainly located mitochondria in HepG2 cells.•In vivo studies, Ir1 has demonstrated the excellent anticancer efficacy irradiated with a 425 nm laser.
Guanidinium-functionalized molecules are commonly studied for their use as pharmaceutically active compounds and drugs carriers. Herein, four cyclometalated iridium(III) complexes containing ...guanidinium ligands have been synthesized and characterized as potential anticancer agents. These complexes exhibit moderate antitumor activity in HeLa, MCF-7, HepG2, CNE-2, and A549 human tumor cells. Interestingly, all complexes showed higher cytotoxicity than cisplatin against a cisplatin-resistant cell line A549R, and less cytotoxicity on the nontumorigenic LO2 cells. Intracellular distribution studies suggest that these complexes are selectively localized in the mitochondria. Mechanism studies indicate that these complexes arrested the cell cycle in the G0/G1 phase and can influence mitochondrial integrity, inducing cancer cell death through reactive oxygen species (ROS)-dependent pathways.
Four cyclometalated iridium(III) complexes containing guanidinium ligands have been synthesized and characterized. These complexes display moderate cytotoxicity by specifically targeting mitochondria and inducing a cascade of apoptotic events related to mitochondrial dysfunction. Display omitted
•Four Ir(III) complexes containing guanidinium ligands were synthesized.•Four complexes displayed higher antiproliferative activities than cisplatin against cisplatin-resistant A549 cells.•Complexes 1 and 2 mainly located mitochondria in HeLa cancer cells.•Complexes 1 and 2 increased ROS production and induced cell cycle arrest in G0/G1 phase.
To investigate the feasibility of optical coherence tomography (OCT)-based digital image correlation (DIC) analysis and to identify the experimental parameters for measurements of polymerization ...shrinkage.
Class I cavities were prepared on bovine incisors and filled with Filtek Z350XT Flowable (Z350F). One OCT image of the polymerized restoration was processed to generate virtually displaced images. In addition, the tooth specimen was physically moved under OCT scanning. A DIC software analyzed these virtual and physical transformation sets and assessed the effects of subset sizes on accuracy. The refractive index of unpolymerized and polymerized Z350F was measured via OCT images. Finally, different particles (70–80 µm glass beads, 150–212 µm glass beads, and 75–150 µm zirconia powder) were added to Z350F to inspect the analyzing quality.
The analyses revealed a high correlation (>99.99%) for virtual movements within 131 pixels (639 µm) and low errors (<5.21%) within a 10-µm physical movement. A subset size of 51 × 51 pixels demonstrated the convergence of correlation coefficients and calculation time. The refractive index of Z350F did not change significantly after polymerization. Adding glass beads or zirconia particles caused light reflection or shielding in OCT images, whereas blank Z350F produced the best DIC analysis results.
The OCT-based DIC analysis with the experimental conditions is feasible in measuring polymerization shrinkage of RBC restorations. The subset size in the DIC analysis should be identified to optimize the analysis conditions and results. Uses of hyper- or hypo-reflective particles is not recommended in this method.
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Background Frailty and sarcopenia are geriatric syndromes of increasing concern and are associated with adverse health outcomes. They are more prevalent among long-term care facility (LTCF) users ...than among community dwellers. Exercise, especially multicomponent and progressive resistance training, is essential for managing these conditions. However, LTCFs, particularly in rural areas, face challenges in implementing structured exercise programs due to health care professional shortages. Moreover, older adults often become bored with repetitive exercise training and may lose interest over time. The Nintendo Switch Ring Fit Adventure (RFA) exergame is a novel exergame that combines resistance, aerobic, and balance exercises and offers a potential solution by boosting motivation in an immersive manner and reducing staff intervention needs. Objective We aimed to evaluate the clinical effectiveness of an exergame-based exercise training program delivered via RFA (exergame-RFA) in improving muscle mass and functional performance among older adult LTCF users. Methods This was a randomized controlled trial conducted from August 2022 to September 2023 and involved older adult LTCF users (aged ≥60 y) in rural southern Taiwan. Participants were randomized into an intervention group (exergame-RFA plus standard care) or a control group (standard care alone). The intervention, conducted seated with arm fit skills and trunk control exercises using the RFA, lasted 30 minutes twice weekly over 12 weeks. The primary outcomes measured were the Study of Osteoporotic Fractures index (serving as an indicator of frailty status) and the diagnostic criteria for sarcopenia (appendicular skeletal muscle mass index, handgrip strength, and gait speed). The secondary outcomes included functional performance (box and block test as well as maximum voluntary isometric contraction of the dominant upper extremity), muscle condition (muscle thickness measured using ultrasonography), activities of daily living (Kihon checklist), health-related quality of life (Short Form Health Survey-36), and cognitive function (brain health test). We used an intention-to-treat analysis, incorporating a simple imputation technique in statistical analysis. A mixed ANOVA, with time as a within-participant factor and intervention as a between-participant factor, was used to compare the training effects on outcomes. Results We recruited 96 individuals, of whom 60 (62%) underwent randomization. Of these 60 participants, 55 (92%) completed the study. Significant group×time interactions were observed in the intervention group in all primary outcomes (all P<.001, except P=.01 for handgrip strength) and most secondary outcomes, including maximum voluntary isometric contraction of the biceps (P=.004) and triceps brachii (P<.001) muscles, biceps muscle thickness measured using ultrasonography (P<.001), box and block test (P<.001), Kihon checklist (physical function: P=.01, mood status: P=.003, and total: P=.003), and brain health test (P<.001). Conclusions The exergame-RFA intervention significantly improved muscle mass, strength, and functional performance among older adult users of rural LTCFs, offering a novel approach to addressing frailty and sarcopenia. Trial Registration ClinicalTrials.gov NCT05360667; https://clinicaltrials.gov/study/NCT05360667 International Registered Report Identifier (IRRID) RR2-10.3389/fmed.2022.1071409
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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