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1.
Sports Health ; : 19417381241262024, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39109891

ABSTRACT

BACKGROUND: Both autoregulatory progressive resistance exercise (APRE) and velocity-based resistance training (VBRT) utilize real-time monitoring of athlete physical performance to adjust training loads to provide appropriate training stimuli. However, the monitoring and adjustment approaches differ between both methods. This study aimed to compare the effects of APRE and VBRT on the muscle strength, power, and agility of college taekwondo athletes. HYPOTHESIS: Eight weeks of APRE and VBRT will promote similar results to strength gains in regards maximal strength, but VBRT will be superior to APRE in explosive power and agility. STUDY DESIGN: Clinical trial. LEVEL OF EVIDENCE: Level 3. METHODS: Thirty taekwondo athletes were divided randomly into 2 groups (VBRT/APRE), and all participants completed an 8-week APRE/VBRT intervention. Maximum strength, explosive power, and agility performance were assessed during the squat 1-repetition maximum (1RM), countermovement jump (CMJ), drop jump (DJ), kicking strength test (KST), taekwondo-specific agility test (TSAT), and hexagon test (HT). RESULTS: Highly significant time effects (P < 0.01) were observed for squat 1RM, CMJ, and TSAT in both the APRE and VBRT groups. However, there were no significant group-by-time differences for any of the measured outcomes to intergroup (P > 0.05), but APRE had a small effect size (ES) over VBRT for CMJ (ES = 0.48, η2p = 0.06), TSAT (ES = 0.26, η2p = 0.02), and HT (ES = 0.42, η2p = 0.05). CONCLUSION: An 8-week autoregulatory APRE and VBRT can both effectively improve both the maximal strength, explosive power, and agility performance of taekwondo athletes, with APRE exhibiting potential advantages in improving CMJ, TSAT, and HT. CLINICAL RELEVANCE: These results provide important insights into the selection of suitable resistance training programs by professional coaches, taking into account athlete needs, training efficiency, and safety considerations.

2.
Pharmaceuticals (Basel) ; 17(7)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-39065688

ABSTRACT

Diabetic retinopathy (DR) remains the leading cause of blindness among the global working-age population. Emerging evidence underscores the significance of diabetic retinal neurodegeneration (DRN) as a pivotal biomarker in the progression of vasculopathy. Inflammation, oxidative stress, neural cell death, and the reduction in neurotrophic factors are the key determinants in the pathophysiology of DRN. Non-apoptotic programmed cell death (PCD) plays a crucial role in regulating stress response, inflammation, and disease management. Therapeutic modalities targeting PCD have shown promising potential for mitigating DRN. In this review, we highlight recent advances in identifying the role of various PCD types in DRN, with specific emphasis on necroptosis, pyroptosis, ferroptosis, parthanatos, and the more recently characterized PANoptosis. In addition, the therapeutic agents aimed at the regulation of PCD for addressing DRN are discussed.

3.
Int Ophthalmol ; 44(1): 249, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38907177

ABSTRACT

OBJECTIVE: To investigate the macular morphological and visual outcomes of combined idiopathic epiretinal membrane (iERM) removal with triamcinolone acetonide (TA) injection based on consideration of the ectopic inner foveal layer (EIFL) staging scheme. METHODS: Retrospective case-control study. The clinical data of 84 eyes of 84 patients who underwent vitrectomy for iERM between 2018 and 2022 were reviewed. The enrolled subjects were divided into the TA and non-TA groups. Fifty-one eyes received intravitreal TA injection following vitrectomy and ERM peeling (TA group), and 33 were only treated by standard vitrectomy and ERM peeling (non-TA group). Preoperative and postoperative EIFL stages, central foveal thickness (CFT), and best-corrected visual acuity (BCVA) were compared between both groups. RESULTS: After a mean follow-up of 7.69 ± 3.68 months, both groups exhibited significant improvement in EIFL stages (P < 0.01), with no discernible advantage observed in the TA group. The TA and non-TA groups demonstrated improvement in the EIFL stages in 56.86 and 63.64% of eyes, respectively (P = 0.43). The CFT and BCVA significantly improved in both groups at the final visit (P < 0.01). However, CFT in the non-TA group displayed a more significant reduction during the follow-up (P < 0.03). Subgroup analysis revealed no significant differences in postoperative CFT and BCVA between the two groups in cases with or without continuous EIFL (P > 0.10). CONCLUSION: Our findings indicate that combined intravitreal TA injection following ERM removal conferred no significant benefits in alleviating macular thickening or improving visual acuity in iERM.


Subject(s)
Epiretinal Membrane , Fovea Centralis , Glucocorticoids , Intravitreal Injections , Tomography, Optical Coherence , Triamcinolone Acetonide , Visual Acuity , Vitrectomy , Humans , Epiretinal Membrane/diagnosis , Epiretinal Membrane/surgery , Retrospective Studies , Male , Female , Tomography, Optical Coherence/methods , Glucocorticoids/administration & dosage , Fovea Centralis/pathology , Vitrectomy/methods , Triamcinolone Acetonide/administration & dosage , Case-Control Studies , Aged , Middle Aged , Follow-Up Studies , Treatment Outcome
4.
PLoS One ; 19(5): e0297878, 2024.
Article in English | MEDLINE | ID: mdl-38753621

ABSTRACT

OBJECTIVE: This study explores the age effects of the sport education model(SEM) on the impact of basic psychological needs (autonomy, competence, relatedness) and intrinsic motivation (interest, enjoyment, satisfaction) among adolescent students. METHOD: Retrieval of relevant literature from PubMed, Web of Science, Scopus, and China National Knowledge Infrastructure (CNKI). The search period ranged from the starting year to January 7, 2024. Subsequently, literature screening, data extraction, and quality assessment will be conducted, and data analysis will be performed using "Review Manager 5.4" software. RESULT: Overall, SEM has a positive and statistically significant impact on the basic psychological needs (MD = 0.36,95% CI [0.22, 0.50]) and intrinsic motivation (MD = 0.75, 95% CI [0.58, 0.93]) of adolescent students (P<0.01). Subgroup analysis revealed age effects on the impact of SEM on the basic psychological needs of adolescent students: pre-peak height velocity (PRE-PHV) (MD = 0.39, 95% CI [0.23, 0.56], I2 = 45%, P<0.01), mid-peak height velocity (MID-PHV) (MD = 0.22, 95% CI [0.01, 0.42], I2 = 82%, P<0.05), post-peak height velocity (POST-PHV) (MD = 1.27, 95% CI [0.79, 1.74], I2 = 0%, P<0.01). Similarly, age effects were found for intrinsic motivation: MID-PHV (MD = 0.86, 95% CI [0.62, 1.11], I2 = 68%, P<0.01), POST-PHV (MD = 0.56, 95% CI [0.40, 0.72], I2 = 0%, P<0.01). CONCLUSION: The SEM is an effective approach to enhancing the basic psychological needs and intrinsic motivation of adolescent students. However, it exhibits age effects among students at different developmental stages. Specifically, in terms of enhancing basic psychological needs, the model has the greatest impact on POST-PHV students, followed by PRE-PHV students, while the improvement effect is relatively lower for MID-PHV students. The enhancement effect on intrinsic motivation diminishes with increasing age.


Subject(s)
Motivation , Sports , Students , Humans , Adolescent , Students/psychology , Sports/psychology , Age Factors , Male , Female
5.
J Exerc Sci Fit ; 22(2): 159-167, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38464602

ABSTRACT

Objectives: Due to the character of the taekwondo, the adenosine triphosphate-phosphocreatine system provides the energy for each kick, the glycolytic system supports the repeated execution of kicks, and the aerobic system promotes recovery between these movements and the bout. Therefore, taekwondo athletes require high explosive power and anaerobic capacity in order to carry out sustained and powerful attacks. So, the purpose of this study is to compare the effects of APRE and VBRT on lower-limb explosive power and anaerobic capacity in college taekwondo players. Methods: A total of 30 taekwondo players completed an 8-week training intervention with autoregulatory progressive resistance exercise (APRE; n = 15) and velocity-based resistance training (VBRT; n = 15). Testing included the one-repetition maximum squat, countermovement jump (CMJ), taekwondo anaerobic intermittent kick test (TAIKT), and 30-s Wingate anaerobic test (WAnT). Results: (1) Intragroup comparisons revealed significant effects for one-repetition maximum squat, peak power of CMJ (CMJPP), relative peak power of CMJ (CMJRPP), and total number of TAIKT (TAIKTTN) in both the APRE and VBRT groups. The VBRT group exhibited small effect sizes for time at peak power of WAnT (WAnTPPT) and moderate effect sizes for peak power of WAnT (WAnTPP), relative peak power of WAnT (WAnTRPP), and fatigue index of TAIKT (TAIKTFI), whereas the APRE group exhibited small effect sizes for TAIKTFI. (2) Intergroup comparisons revealed no significant effects in any of the results. However, VBRT demonstrated a moderate advantage in WAnTPP and WAnTRPP, whereas APRE had a small advantage in CMJPP and CMJRPP. Conclusions: These findings suggest that APRE improved explosive power (CMJPP and CMJRPP) more, whereas VBRT improved anaerobic power output (WAnTPP and WAnTRPP) more. Both methods were found to have similar effects in improving the anaerobic endurance (WAnTPPT and TAIKTTN) and fatigue index (power drop of WAnT and TAIKTFI).

6.
BMC Ophthalmol ; 24(1): 102, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38443874

ABSTRACT

BACKGROUND: This study aimed to investigate the functional and anatomical outcomes of subthreshold micropulse laser (SMPL) therapy in eyes with early postoperative macular thickening after idiopathic epiretinal membrane (iERM) removal. METHODS: This was a prospective and interventional study. Forty-eight eyes from 48 patients with macular edema at 1 month after iERM removal were randomly divided into two groups. Patients in the SMPL group (n = 24) received SMPL therapy while no special intervention was used for the observation group (n = 24). Baseline demographic data and clinical findings before and at 1 and 3 months after SMPL treatment or observation, including best-corrected visual acuity (BCVA) and the changes in central subfield thickness (CST) and average macular thickness (AMT), were analyzed. RESULTS: An improvement in BCVA with a decrease in CST and AMT from baseline to the 3-month follow-ups were observed in both SMPL and observation groups. No significant difference in BCVA was observed between the SMPL group and observation group either in the 1-month (0.26 [0.15, 0.52] vs. 0.26 [0.15, 0.39], P = 0.852) or the 3-month (0.15 [0.10, 0.30] vs. 0.23 [0.15, 0.30], P = 0.329) follow-up. There was a greater reduction in CST in the SMPL group versus observation group between baseline and the 3-month follow-up (-77.8 ± 72.3 µm vs. -45.0 ± 46.9 µm, P = 0.049). The alteration in AMT did not differ between the two groups in either 1-month (-16.5 ± 20.1 µm vs. -19.7 ± 16.3 µm, P = 0.547) or 3-month (-36.9 ± 26.9 µm vs. -34.0 ± 20.1 µm, P = 0.678) follow-up. CONCLUSIONS: SMPL therapy led to a significant decrease in CST at the 3-month follow-up while did not significantly improve the visual acuity in patients with postoperative macular thickening following iERM surgery. TRIAL REGISTRATION: The study was registered on Aug 27, 2020 (Trial Registration Number: ChiCTR 2000037227).


Subject(s)
Epiretinal Membrane , Laser Therapy , Low-Level Light Therapy , Humans , Epiretinal Membrane/surgery , Prospective Studies , Eye , Vision Disorders
8.
ACS Appl Mater Interfaces ; 16(5): 6068-6077, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38258520

ABSTRACT

Deep-level defects in ß-Ga2O3 that worsen the response speed and dark current (Id) of photodetectors (PDs) have been a long-standing issue for its application. Herein, an in situ grown single-crystal Ga2O3 nanoparticle seed layer (NPSL) was used to shorten the response time and reduce the Id of metal-semiconductor-metal (MSM) PDs. With the NPSL, the Id was reduced by 4 magnitudes from 0.389 µA to 81.03 pA, and the decay time (τd1/τd2) decreased from 258/1690 to 62/142 µs at -5 V. In addition, the PDs with the NPSL also exhibit a high responsivity (43.5 A W-1), high specific detectivity (2.81 × 1014 Jones), and large linear dynamic range (61 dB) under 254 nm illumination. The mechanism behind the performance improvement can be attributed to the suppression of the deep-level defects (i.e., self-trapped holes) and increase of the Schottky barrier. The barrier height extracted is increased by 0.18 eV compared with the case without the NPSL. Our work contributes to understanding the relationship between defects and the performance of PDs based on heteroepitaxial ß-Ga2O3 thin films and provides an important reference for the development of high-speed and ultrasensitive deep ultraviolet PDs.

9.
J Strength Cond Res ; 38(4): 656-670, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38048589

ABSTRACT

ABSTRACT: Zhang, M, Chen, L, Dai, J, Yang, Q, Huang, Z, He, J, Ji, H, Sun, J, and Li, D. Application of a new monitoring variable: Effects of power loss during squat training on strength gains and sports performance. J Strength Cond Res 38(4): 656-670, 2024-This study aimed to compare the effects of power loss (PL) autoregulated volume (PL10 and PL20) with standardized fixed-load (FL) prescription on strength, sports performance, and lean body mass (LBM). Thirty-five female basketball players from a sports college were randomly assigned to 3 experimental groups (PL10, n = 12; PL20, n = 12; and FL, n = 11, respectively) that performed a resistance training (RT) program with wave-like periodization for 10 weeks using the back squat exercise. Assessments performed before (Pre) and after (Post) intervention included assessed 1 repetition maximum (1RM), body composition, 20-m sprint (T20M), change of direction (COD), and jump performance, including countermovement jump with arm swing, maximum vertical jump, and reactive strength index. Three groups showed significant improvements in strength (effect size [ES]: PL10 = 2.98, PL20 = 3.14, and FL = 1.90; p < 0.001) and jump performance (ES: PL10 = 0.74, PL20 = 1.50, and FL = 0.50; p <0.05-0.001). However, PL10 and PL20 demonstrated different advantages in sports performance compared with FL (group × time interaction, p <0.05). Specifically, PL10 significantly improved COD performance (ES = -0.79 ∼ -0.53, p <0.01), whereas PL20 showed greater improvements in sprint (ES = -0.57, p <0.05) and jump performance (ES = 0.67-1.64, p <0.01-0.001). Moreover, PL10 resulted in similar gains to PL20 and beneficial improvements compared with FL in LBM, despite performing the least repetitions. Overall, the study indicates that power loss-based autoregulation induces greater gains in LBM and sports performance, as well as eliciting a higher efficiency dose response than standardized FL prescriptions, particularly for PL10. Therefore, incorporating PL monitoring in training programs is recommended, and further studies on power-based RT would be worthwhile.


Subject(s)
Athletic Performance , Basketball , Resistance Training , Humans , Female , Muscle Strength/physiology , Athletic Performance/physiology , Resistance Training/methods , Body Composition
10.
Sci Rep ; 13(1): 21222, 2023 12 01.
Article in English | MEDLINE | ID: mdl-38040837

ABSTRACT

Plyometric training boosts adolescents' jumping ability, crucial for athletic success and health. However, the best total ground contact frequency (TGCF) and overall intervention time (OIT) for these exercises remain unclear. This meta-analysis aims to identify optimal TGCF and OIT in plyometric training for adolescents, focusing on countermovement jump (CMJ) and squat jump (SJ) outcomes. This systematic review encompassed five databases and included 38 studies with 50 randomized controlled experiments and 3347 participants. We used the Cochrane risk assessment tool for study quality and Review Manager 5.4 for data analysis. The current meta-analysis incorporated a total of 38 studies, comprising 50 sets of randomized controlled trials, to investigate the influence of different TGCFs and OITs on plyometric training. The Cochrane risk assessment tool indicated that all the included studies were classified as low risk. Various TGCFs in plyometric training positively affected CMJ and SJ heights in adolescents. The TGCF of less than 900 was ideal for enhancing CMJ, whereas more than 1400 was effective for SJ. The optimal OIT was 400-600 min, specifically, 500-600 min for CMJ and 400-500 min for SJ. Plyometric training improves jumping ability in adolescents. Lower ground contact frequency (< 900 contacts) enhances CMJ, while higher ground contact frequency (> 1400 contacts) is more effective for SJ. Optimal intervention time ranges from 400 to 600 min, with 500 to 600 min benefiting CMJ and 400 to 500 min improving SJ.


Subject(s)
Athletic Performance , Plyometric Exercise , Humans , Adolescent , Exercise , Posture , Muscle Strength
11.
Database (Oxford) ; 20232023 Dec 18.
Article in English | MEDLINE | ID: mdl-38109881

ABSTRACT

The aim of the study is to establish an online database for predicting protein structures altered in ocular diseases by Alphafold2 and RoseTTAFold algorithms. Totally, 726 genes of multiple ocular diseases were collected for protein structure prediction. Both Alphafold2 and RoseTTAFold algorithms were built locally using the open-source codebases. A dataset with 48 protein structures from Protein Data Bank (PDB) was adopted for algorithm set-up validation. A website was built to match ocular genes with the corresponding predicted tertiary protein structures for each amino acid sequence. The predicted local distance difference test-Cα (pLDDT) and template modeling (TM) scores of the validation protein structure and the selected ocular genes were evaluated. Molecular dynamics and molecular docking simulations were performed to demonstrate the applications of the predicted structures. For the validation dataset, 70.8% of the predicted protein structures showed pLDDT greater than 90. Compared to the PDB structures, 100% of the AlphaFold2-predicted structures and 97.9% of the RoseTTAFold-predicted structure showed TM score greater than 0.5. Totally, 1329 amino acid sequences of 430 ocular disease-related genes have been predicted, of which 75.9% showed pLDDT greater than 70 for the wildtype sequences and 76.1% for the variant sequences. Small molecule docking and molecular dynamics simulations revealed that the predicted protein structures with higher confidence scores showed similar molecular characteristics with the structures from PDB. We have developed an ocular protein structure database (EyeProdb) for ocular disease, which is released for the public and will facilitate the biological investigations and structure-based drug development for ocular diseases. Database URL:  http://eyeprodb.jsiec.org.


Subject(s)
Artificial Intelligence , Eye Diseases , Humans , Molecular Docking Simulation , Proteins/chemistry , Algorithms , Eye Diseases/genetics , Databases, Protein , Protein Conformation
12.
Biomolecules ; 13(10)2023 10 17.
Article in English | MEDLINE | ID: mdl-37892214

ABSTRACT

Hypoxia-induced retinal neovascularization is a leading cause of blindness worldwide. Oxygen-induced retinopathy (OIR) mouse, a well-established angiogenesis model, has been extensively used to evaluate the effect of anti-angiogenic agents through intravitreal injection. Here, we serendipitously found that the needles used for intravitreal injection caused an unexpected "anti-angiogenic" effect in the OIR mice. To evaluate the effects of various intravitreal puncture sizes on retinal neovascularization and explore the potential underlying mechanism, intravitreal punctures using 0.5 mm (25 G), 0.3 mm (30 G), or 0.21 mm (33 G) needles were performed in OIR mice. Compared with 0.3 mm and 0.21 mm puncture, the 0.5 mm puncture remarkably suppressed the formation of pathological angiogenesis, inhibited vascular leakage, and remodeled the retinal vasculature. Mechanistically, the 0.5 mm puncture induced a substantial reduction in intraocular pressure (IOP), leading to an improvement in oxygen partial pressure (pO2) and significant reduction in Hif1a expression, resulting in resolution of angiogenic and inflammatory responses. Furthermore, IOP-lowering drugs, Travatan or Azarga, also promoted the alleviation of hypoxia and exhibited a potent anti-angiogenesis efficacy. Our study revealed an acute and significant reduction in IOP caused by a large puncture, which could remarkably suppress HIF-1α-mediated retinal neovascularization, indicating that lowering IOP may be a promising therapeutic avenue for treating retinal neovascular diseases.


Subject(s)
Retinal Diseases , Retinal Neovascularization , Animals , Mice , Retinal Neovascularization/metabolism , Intraocular Pressure , Neovascularization, Pathologic/drug therapy , Oxygen/therapeutic use , Hypoxia/drug therapy , Hypoxia/metabolism , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/therapeutic use , Mice, Inbred C57BL
13.
PeerJ ; 11: e15877, 2023.
Article in English | MEDLINE | ID: mdl-37576500

ABSTRACT

Objectives: Jumping ability has been identified as a key factor that influences the performance of badminton athletes. Autoregulatory progressive resistance exercise (APRE) and velocity-based resistance training (VBRT) are commonly used approaches to enhance muscle strength and have been shown to accurately monitor the development of explosive power to improve jumping ability. This study aims to investigate the effects of APRE and VBRT on badminton athletes' jumping ability and to provide practical insights into improving their jumping performance during competitions. Methods: Upon completing familiarization and pretesting, 18 badminton athletes were included and completed the training intervention (age, 21.4 ± 1.4 years; stature, 170.1 ± 7.3 cm; body mass, 65.9 ± 12 kg); they were randomly divided into the APRE group (n = 9) and VBRT group (n = 9). Jumping performance was assessed during the countermovement jump (CMJ), squat jump (SJ), and drop jump (DJ) via SmartJump, with CMJ 's and SJ's jump height, eccentric utilization ratio (EUR), and reactive strength index (RSI). All participants then completed a 4-week in-season resistance training intervention. Results: (1) The results of the within-group indicated that only the CMJ (pre: 41.56 ± 7.84 vs post: 43.57 ± 7.85, p < 0.05) of the APRE group had significant differences, whereas the SJ, EUR, and RSI were not significantly different (p > 0.05). (2) The results of the intergroups revealed that all indicators had no significant differences (p > 0.05), but APRE had a moderate effect size on the improvement of the CMJ (η2 = 0.244) and EUR (η2 = 0.068) when compared with VBRT. Conclusions: The results showed that, compared to VBRT, APRE can effectively improve the performance of the reactive athletes' lower limb explosive power in the CMJ in a shorter period of time. The findings indicate that APRE may be useful for coaches seeking to improve the CMJ performance of athletes in the short term.


Subject(s)
Racquet Sports , Resistance Training , Adult , Humans , Young Adult , Athletes , Exercise , Muscle Strength/physiology , Resistance Training/methods
14.
J Diabetes ; 15(10): 866-880, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37403338

ABSTRACT

AIMS: Diabetic retinopathy (DR) is a significant global public health concern. Alternative, safe, and cost-effective pharmacologic approaches are warranted. We aimed to investigate the therapeutic potential of nattokinase (NK) for early DR and the underlying molecular mechanism. METHODS: A mouse model of diabetes induced by streptozotocin was utilized and NK was administered via intravitreal injection. Microvascular abnormities were evaluated by examining the leakage from blood-retinal barrier dysfunction and loss of pericytes. Retinal neuroinflammation was examined through the assessment of glial activation and leukostasis. The level of high mobility group box 1 (HMGB1) and its downstream signaling molecules was evaluated following NK treatment. RESULTS: NK administration significantly improved the blood-retinal barrier function and rescued pericyte loss in the diabetic retinas. Additionally, NK treatment inhibited diabetes-induced gliosis and inflammatory response and protected retinal neurons from diabetes-induced injury. NK also improved high glucose-induced dysfunction in cultured human retinal micrangium endothelial cells. Mechanistically, NK regulated diabetes-induced inflammation partially by modulating HMGB1 signaling in the activated microglia. CONCLUSIONS: This study demonstrated the protective effects of NK against microvascular damages and neuroinflammation in the streptozotocin-induced DR model, suggesting that NK could be a potential pharmaceutical agent for the treatment of DR.

16.
Mol Oral Microbiol ; 2023 Jun 22.
Article in English | MEDLINE | ID: mdl-37347649

ABSTRACT

INTRODUCTION: This study aimed to investigate the effect of Stat3 on the osteoblast-mediated bone healing in the inflammatory lesion. METHODS: The conditional knockout of Stat3 in osteoblasts (Stat3 CKO) was generated via the Cre-loxP recombination system using Osterix-Cre transgenic mice. The calvarial bone inflammatory lesions were established on both Stat3 CKO and wild-type mice, then harvested to assess the bone healing. In response to lipopolysaccharide (LPS) stimulation, osteoblasts from Stat3 CKO and wild-type mice were subjected to examine the formation of calcium deposits, the expression of osteogenic markers (i.e., Runx2, OPN, COL1A1), and osteoclast-related markers (i.e., RANKL, OPG). The EdU and transwell assays were performed to assess the proliferation and migration of the cells. RESULTS: A decrease in bone mass and an increase in osteolysis were found in the inflammatory lesions on Stat3 CKO mice when compared with the control. More osteoclastic-like cells and an increased expression of RANKL were observed in Stat3 CKO mice. Both mRNA and protein expressions of Stat3 and osteogenic markers in the lesions were significantly decreased in Stat3 CKO mice. After co-cultured with osteogenic medium, the Stat3-deficient osteoblasts were found with a significant decrease in calcium deposits and the expression of osteogenic markers, and with a significant increased expression of RANKL. The impaired ossification of Stat3-deficient osteoblasts was even more pronounced with the presence of lipopolysaccharides in vitro. The most decrease in cell proliferation and migration was found in Stat3-deficient osteoblasts in response to LPS. CONCLUSIONS: Loss of Stat3 in osteoblasts impaired bone healing in an inflammatory microenvironment.

20.
Cell Death Dis ; 14(3): 227, 2023 03 29.
Article in English | MEDLINE | ID: mdl-36991017

ABSTRACT

Diabetic retinopathy (DR) is a leading cause of blindness that poses significant public health concerns worldwide. Increasing evidence suggests that neuroinflammation plays a key role in the early stages of DR. Microglia, long-lived immune cells in the central nervous system, can become activated in response to pathological insults and contribute to retinal neuroinflammation. However, the molecular mechanisms of microglial activation during the early stages of DR are not fully understood. In this study, we used in vivo and in vitro assays to investigate the role of microglial activation in the early pathogenesis of DR. We found that activated microglia triggered an inflammatory cascade through a process called necroptosis, a newly discovered pathway of regulated cell death. In the diabetic retina, key components of the necroptotic machinery, including RIP1, RIP3, and MLKL, were highly expressed and mainly localized in activated microglia. Knockdown of RIP3 in DR mice reduced microglial necroptosis and decreased pro-inflammatory cytokines. Additionally, blocking necroptosis with the specific inhibitor GSK-872 improved retinal neuroinflammation and neurodegeneration, as well as visual function in diabetic mice. RIP3-mediated necroptosis was activated and contributed to inflammation in BV2 microglia under hyperglycaemic conditions. Our data demonstrate the importance of microglial necroptosis in retinal neuroinflammation related to diabetes and suggest that targeting necroptosis in microglia may be a promising therapeutic strategy for the early stages of DR.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Retinopathy , Animals , Mice , Diabetes Mellitus, Experimental/metabolism , Diabetic Retinopathy/genetics , Diabetic Retinopathy/metabolism , Microglia/metabolism , Necroptosis/physiology , Neuroinflammatory Diseases , Protein Kinases/metabolism , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism
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