Glyoxalase 1: Emerging biomarker and therapeutic target in cervical cancer progression.

INTRODUCTION: Cervical cancer presents a significant global health challenge, disproportionately impacting underserved populations with limited access to healthcare. Early detection and effective management are vital in addressing this public health concern. This study focuses on Glyoxalase-1 (GLO1), an enzyme crucial for methylglyoxal detoxification, in the context of cervical cancer. METHODS: We assessed GLO1 expression in cervical cancer patient samples using immunohistochemistry. In vitro experiments using HeLa cells were conducted to evaluate the impact of GLO1 inhibition on cell viability and migration. Single-cell RNA sequencing (scRNA-seq) and gene set variation analysis were utilized to investigate the role of GLO1 in the metabolism of cervical cancer. Additionally, public microarray data were analyzed to determine GLO1 expression across various stages of cervical cancer. RESULTS: Our analysis included 58 cervical cancer patients, and showed that GLO1 is significantly upregulated in cervical cancer tissues compared to normal cervical tissues, independent of pathological findings and disease stage. In vitro experiments indicated that GLO1 inhibition by S-p-bromobenzylglutathione cyclopentyl diester decreased cell viability and migration in cervical cancer cell lines. Analyses of scRNA-seq data and public gene expression datasets corroborated the overexpression of GLO1 and its involvement in cancer metabolism, particularly glycolysis. An examination of expression data from precancerous lesions revealed a progressive increase in GLO1 expression from normal tissue to invasive cervical cancer. CONCLUSIONS: This study highlights the critical role of GLO1 in the progression of cervical cancer, presenting it as a potential biomarker and therapeutic target. These findings contribute valuable insights towards personalized treatment approaches and augment the ongoing efforts to combat cervical cancer. Further research is necessary to comprehensively explore GLO1's potential in clinical applications.

Does Radial Extracorporeal Shockwave Therapy Applied to the Achilles Tendon Influence Ankle Functionality?

This study aimed to determine the effectiveness of radial extracorporeal shockwave therapy (rESWT) in enhancing ankle function in patients with Achilles tendon injuries. The choice of rESWT was based on previous success in the treatment of musculoskeletal conditions. The study involved an intervention group that received rESWT, and a control group that received sham therapy. The results revealed that rESWT led to significant improvements in single-leg vertical jump (d = 0.55, p < 0.05), indicating enhanced power generation and ankle functionality that were not observed in the control group. Additionally, the therapy resulted in increased ankle mobility, as observed by improvements in plantar flexion and heel-rise tests. Interestingly, these functional gains were not accompanied by changes in the Achilles tendon stiffness, suggesting that the benefits of rESWT may be more functional than structural. This study highlights rESWT as a promising tool for rehabilitation, particularly following Achilles tendon injuries. The study concluded that, although rESWT appears to improve certain aspects of ankle function, further studies with a larger and more diverse population over a longer period are necessary to confirm these findings and establish comprehensive treatment protocols.

Interruption of p38MAPK-MSK1-CREB-MITF-M pathway to prevent hyperpigmentation in the skin.

Background: Melanocortin 1 receptor (MC1R), a receptor of α-melanocyte-stimulating hormone (α-MSH), is exclusively present in melanocytes where α-MSH/MC1R stimulate melanin pigmentation through microphthalmia-associated transcription factor M (MITF-M). Toll-like receptor 4 (TLR4), a receptor of endotoxin lipopolysaccharide (LPS), is distributed in immune and other cell types including melanocytes where LPS/TLR4 activate transcriptional activity of nuclear factor (NF)-κB to express cytokines in innate immunity. LPS/TLR4 also up-regulate MITF-M-target melanogenic genes in melanocytes. Here, we propose a molecular target of antimelanogenic activity through elucidating inhibitory mechanism on α-MSH-induced melanogenic programs by benzimidazole-2-butanol (BI2B), an inhibitor of LPS/TLR4-activated transcriptional activity of NF-κB. Methods: Ultraviolet B (UV-B)-irradiated skins of HRM-2 hairless mice and α-MSH-activated melanocyte cultures were employed to examine melanogenic programs. Results: Topical treatment with BI2B ameliorated UV-B-irradiated skin hyperpigmentation in mice. BI2B suppressed the protein or mRNA levels of melanogenic markers, such as tyrosinase (TYR), MITF-M and proopiomelanocortin (POMC), in UV-B-exposed and pigmented skin tissues. Moreover, BI2B inhibited melanin pigmentation in UV-B-irradiated co-cultures of keratinocyte and melanocyte cells and that in α-MSH-activated melanocyte cultures. Mechanistically, BI2B inhibited the activation of cAMP response element-binding protein (CREB) in α-MSH-induced melanogenic programs and suppressed the expression of MITF-M at the promoter level. As a molecular target, BI2B primarily inhibited mitogen-activated protein kinase (MAPK) kinase 3 (MKK3)-catalyzed kinase activity on p38MAPK. Subsequently, BI2B interrupted downstream pathway of p38MAPK-mitogen and stress-activated protein kinase-1 (MSK1)-CREB-MITF-M, and suppressed MITF-M-target melanogenic genes, encoding enzymes TYR, TYR-related protein-1 (TRP-1) and dopachrome tautomerase (DCT) in melanin biosynthesis, and encoding proteins PMEL17 and Rab27A in the transfer of pigmented melanosomes to the overlaying keratinocytes in the skin. Conclusion: Targeting the MKK3-p38MAPK-MSK1-CREB-MITF-M pathway was suggested as a rationale to inhibit UV-B- or α-MSH-induced facultative melanogenesis and as a strategy to prevent acquired pigmentary disorders in the skin.

Developing an Online Health Community Platform for Facilitating Empowerment in Chronic Disease Prevention and Health Promotion.

This study aimed to develop an online health community platform for facilitating the empowerment of people with chronic diseases dwelling in the community regarding disease prevention and health promotion. The user-centered design approach included four main steps: (1) identifying the health problems and needs of target users, (2) developing the content of the platform, (3) constructing the platform, and (4) pilot testing, refinement, and finalization. An online health community platform available both in a mobile application and a Web-enabled application has been launched to facilitate empowerment and self-management by people with chronic conditions. The main components of the application comprised (1) screening for chronic diseases and health problems, (2) setting personal goals for health promotion and action planning to achieve the goals themselves, (3) offering an online health community with shared group goals that help users engage with their peers to attain their goals, and (4) creating one's own online health community and inviting others to participate. The platform has the potential to encourage people with chronic conditions to proactively engage in their own health promotion. Future studies are needed to determine the impact of the application on self-management and empowerment for its users.

Decision aids for promoting shared decision-making: A review of systematic reviews.

In the context of shared decision-making (SDM), experts have advocated the use of validated decision aids (DAs) as valuable tools for facilitating SDM in various healthcare scenarios. This comprehensive review attempts to analyze a vast corpus of DA research by performing thorough searches across four prominent databases (PubMed, CINAHL, Embase, and Web of Science). Independent reviewers selected relevant reviews, extracted data, and assessed review quality using the AMSTAR II tool. A total of 34 systematic reviews were identified and evaluated in this review, encompassing a wide range of outcomes associated with using DAs. These outcomes include patient knowledge, patient involvement in SDM, decision conflict, decision regret, satisfaction, and adherence. In addition, DAs positively affect healthcare provider outcomes by increasing satisfaction, reducing decision conflicts, and lengthening clinical consultations. This review highlights the need for additional research in specific contexts such as long-term care, mental health, and reproductive health to better understand the benefits and challenges of implementing DAs in these settings. Such research can contribute to the improvement of SDM practices and patient-centered care.

Comparison of the Influence of Dual-Task Activities on Prefrontal Activation and Gait Variables in Older Adults with Mild Cognitive Impairment during Straight and Curved Walking.

Background and Objectives: Mild cognitive impairment (MCI) is an early stage of dementia in which everyday tasks can be maintained; however, notable challenges may occur in memory, focus, and problem-solving skills. Therefore, motor-cognitive dual-task training is warranted to prevent cognitive decline and improve cognition in aging populations. This study aimed to determine the influence of such dual-task activities during straight and curved walking on the activities of the prefrontal cortex and associated gait variables in older adults with MCI. Materials and Methods: Twenty-seven older adults aged ≥65 years and identified as having MCI based on their scores (18-23) on the Korean Mini-Mental State Examination were enrolled. The participants performed four task scenarios in random order: walking straight, walking straight with a cognitive task, walking curved, and walking curved with a cognitive task. The activation of the prefrontal cortex, which is manifested by a change in the level of oxyhemoglobin, was measured using functional near-infrared spectroscopy. The gait speed and step count were recorded during the task performance. Results: Significant differences were observed in prefrontal cortex activation and gait variables (p < 0.05). Specifically, a substantial increase was observed in prefrontal cortex activation during a dual task compared with that during a resting-state (p < 0.013). Additionally, significant variations were noted in the gait speed and step count (p < 0.05). Conclusions: This study directly demonstrates the impact of motor-cognitive dual-task training on prefrontal cortex activation in older adults with MCI, suggesting the importance of including such interventions in enhancing cognitive function.

Human Pluripotent Stem Cell-Derived Alveolar Organoids: Cellular Heterogeneity and Maturity.

Chronic respiratory diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and respiratory infections injure the alveoli; the damage evoked is mostly irreversible and occasionally leads to death. Achieving a detailed understanding of the pathogenesis of these fatal respiratory diseases has been hampered by limited access to human alveolar tissue and the differences between mice and humans. Thus, the development of human alveolar organoid (AO) models that mimic in vivo physiology and pathophysiology has gained tremendous attention over the last decade. In recent years, human pluripotent stem cells (hPSCs) have been successfully employed to generate several types of organoids representing different respiratory compartments, including alveolar regions. However, despite continued advances in three-dimensional culture techniques and single-cell genomics, there is still a profound need to improve the cellular heterogeneity and maturity of AOs to recapitulate the key histological and functional features of in vivo alveolar tissue. In particular, the incorporation of immune cells such as macrophages into hPSC-AO systems is crucial for disease modeling and subsequent drug screening. In this review, we summarize current methods for differentiating alveolar epithelial cells from hPSCs followed by AO generation and their applications in disease modeling, drug testing, and toxicity evaluation. In addition, we review how current hPSC-AOs closely resemble in vivo alveoli in terms of phenotype, cellular heterogeneity, and maturity.

Transcriptional Response of Pectobacterium carotovorum to Cinnamaldehyde Treatment.

Cinnamaldehyde is a natural compound extracted from cinnamon bark essential oil, acclaimed for its versatile properties in both pharmaceutical and agricultural fields, including antimicrobial, antioxidant, and anticancer activities. Although potential of cinnamaldehyde against plant pathogenic bacteria like Agrobacterium tumefaciens and Pseudomonas syringae pv. actinidiae causative agents of crown gall and bacterial canker diseases, respectively has been documented, indepth studies into cinnamaldehyde's broader influence on plant pathogenic bacteria are relatively unexplored. Particularly, Pectobacterium spp., gram-negative soil-borne pathogens, notoriously cause soft rot damage across a spectrum of plant families, emphasizing the urgency for effective treatments. Our investigation established that the Minimum Inhibitory Concentrations (MICs) of cinnamaldehyde against strains P. odoriferum JK2, P. carotovorum BP201601, and P. versatile MYP201603 were 250 µg/ml, 125 µg/ml, and 125 µg/ml, respectively. Concurrently, their Minimum Bactericidal Concentrations (MBCs) were found to be 500 µg/ml, 250 µg/ml, and 500 µg/ml, respectively. Using RNA-sequencing analysis, we identified 1,907 differentially expressed genes in P. carotovorum BP201601 treated with 500 µg/ml cinnamaldehyde. Notably, our results indicate that cinnamaldehyde upregulated nitrate reductase pathways while downregulating the citrate cycle, suggesting a potential disruption in the aerobic respiration system of P. carotovorum during cinnamaldehyde exposure. This study serves as a pioneering exploration of the transcriptional response of P. carotovorum to cinnamaldehyde, providing insights into the bactericidal mechanisms employed by cinnamaldehyde against this bacterium.

Immediate Effects of Sprinter-Pattern Exercise on the Lordotic Curve and Abdominal Muscle Activity in Individuals with Hyperlordosis.

Background and Objectives: Abdominal muscle exercises with limb movements are more effective for trunk stabilization than traditional exercises involving trunk flexion alone. This study examined the effects of abdominal exercises incorporating sprinter pattern and crunch exercises on changes in the lordotic curve and abdominal muscle activation in individuals with low back pain caused by hyperlordosis resulting from weak abdominal muscles. Materials and Methods: In this single-blind, randomized controlled trial, a total of 40 participants with hyperlordosis were recruited and randomly assigned to perform either sprinter-pattern abdominal exercises or crunch exercises. The participants assigned to each group performed three sets of ten abdominal exercises. The lumbar lordotic angle (LLA) and sacrohorizontal angle (SHA) were assessed prior to and following the intervention, whereas abdominal muscle activity was gauged throughout the intervention period. Changes in the LLA and SHA were measured by radiography. Abdominal muscle activity was measured using electromyography. Results: The LLA and SHA decreased significantly in both groups (p < 0.001), while the sprinter-pattern exercise group showed a statistically significant decrease compared to the crunch exercise group (p < 0.001). In the activity of the abdominal muscles, there was no significant difference in the rectus abdominis muscle between the two groups (p > 0.005). However, a significant difference between the external and internal oblique muscles was observed, and the activities of both muscles were significantly higher in the sprinter-pattern exercise group than in the crunch exercise group (p < 0.005). Conclusions: Abdominal exercise using a sprinter pattern may be effective in reducing lumbar lordosis by strengthening the abdominal muscles in patients with hyperlordosis.

Utilization of Mirror Visual Feedback for Upper Limb Function in Poststroke Patients: A Systematic Review and Meta-Analysis.

Mirror visual feedback (MVF), a noninvasive treatment method, is attracting attention as a possibility to promote the recovery of upper limb function in stroke patients. However, the cognitive effects of this therapy have received limited attention in the existing literature. To address this gap, we conducted a systematic review and meta-analysis to investigate the relationship between upper limb function and cognition in stroke patients and to evaluate the effect of MVF on improving upper limb function. A comprehensive search was performed on the Embase, MEDLINE, and PubMed databases to identify original articles and clinical studies published between 2013 and 2022. Qualitative analysis was performed using the Cochrane Risk of Bias tool, and in the quantitative analysis, a random-effects model was used as the effect model, and standard mean difference (SMD) was used as the effect measure. Eight studies that met the inclusion criteria were entered in the analysis. Data extraction included an assessment tool for upper extremity function. Results of the quantitative analysis demonstrate that MVF was effective in improving upper extremity function in stroke patients (SMD = 0.94, 95% CI 0.69 to 1.20). In conclusion, this systematic review and meta-analysis provides evidence supporting the effectiveness of MVF in improving upper limb function in stroke patients. However, further studies are needed to investigate the cognitive effects of MVF and elucidate the underlying mechanisms.

Solvent Engineering for Nonpolar Substrate Glycosylation Catalyzed by the UDP-Glucose-Dependent Glycosyltransferase UGT71E5: Intensification of the Synthesis of 15-Hydroxy Cinmethylin ß-d-Glucoside.

Sugar nucleotide-dependent glycosyltransferases are powerful catalysts of the glycosylation of natural products and xenobiotics. The low solubility of the aglycone substrate often limits the synthetic efficiency of the transformation catalyzed. Here, we explored different approaches of solvent engineering for reaction intensification of ß-glycosylation of 15HCM (a C15-hydroxylated, plant detoxification metabolite of the herbicide cinmethylin) catalyzed by safflower UGT71E5 using UDP-glucose as the donor substrate. Use of a cosolvent (DMSO, ethanol, and acetonitrile; ≤50 vol %) or a water-immiscible solvent (n-dodecane, n-heptane, n-hexane, and 1-hexene) was ineffective due to enzyme activity and stability, both impaired ≥10-fold compared to a pure aqueous solvent. Complexation in 2-hydroxypropyl-ß-cyclodextrin enabled dissolution of 50 mM 15HCM while retaining the UGT71E5 activity (∼0.32 U/mg) and stability. Using UDP-glucose recycling, 15HCM was converted completely, and 15HCM ß-d-glucoside was isolated in 90% yield (∼150 mg). Collectively, this study highlights the requirement for a mild, enzyme-compatible strategy for aglycone solubility enhancement in glycosyltransferase catalysis applied to glycoside synthesis.

Soft-Tissue Mobilization and Pain Neuroscience Education for Chronic Nonspecific Low Back Pain with Central Sensitization: A Prospective Randomized Single-Blind Controlled Trial.

This study was conducted to demonstrate the therapeutic effect of soft-tissue mobilization (STM) combined with pain neuroscience education (PNE) for patients with chronic nonspecific low back pain with central sensitization. A total of 28 participants were recruited and randomly allocated to either the STM group (SMG) (n = 14) or the STM plus PNE group (BG; blended group) (n = 14). STM was applied twice a week for four weeks, with a total of eight sessions, and PNE was applied within four weeks, for a total of two sessions. The primary outcome was pain intensity, and the secondary outcomes were central sensitization, pressure pain, pain cognition, and disability. Measurements were made at baseline, after the test, and at 2-week and 4-week follow-ups. The BG showed significant improvement in pain intensity (p < 0.001), pressure pain (p < 0.001), disability (p < 0.001), and pain cognition (p < 0.001) compared to the SMG. This study demonstrated that STM plus PNE is more effective for all measured outcomes compared to STM alone. This finding suggests that the combination of PNE and manual therapy has a positive effect on pain, disability index, and psychological factors in the short term.

Exercise-Induced Fibroblast Growth Factor-21: A Systematic Review and Meta-Analysis.

This systematic review aimed to synthesize and quantify the results of the studies investigating the changes in fibroblast growth factor-21 (FGF-21) induced by exercise. We searched for studies that did not differentiate between patients and healthy adults but compared them before and after exercise and with and without exercise. For quality assessment, the risk-of-bias assessment tool for nonrandomized studies and the Cochrane risk-of-bias tool were used. A quantitative analysis was performed using the standardized mean difference (SMD) and random-effects model in RevMan 5.4. A total of 94 studies were searched in international electronic databases, and after screening, 10 studies with 376 participants were analyzed. Compared with no exercise, there was a significant increase in the FGF-21 levels from before to after exercise (SMD = 1.05, 95% confidence interval (CI), 0.21 to 1.89). The changes in FGF-21 levels in the exercise group showed a significant difference from the levels in the controls. The results of the random-effects model were as follows: SMD = 1.12; 95% CI, -0.13 to 2.37. While the data on acute exercise were not synthesized in this study, FGF-21 levels generally increased after chronic exercise compared with no exercise.

Therapeutic and Preventive Effect of Orally Administered Prebiotics on Atopic Dermatitis in a Mouse Model.

PURPOSE: Recently, interest is increasing in using prebiotics, which are nutrient ingredients of live microorganism that improve the intestinal environments by promoting the growth of beneficial gut microflora. Although numerous studies have demonstrated the beneficial effects of probiotics on atopic dermatitis (AD) development, few have examined preventive and therapeutic effects of prebiotics on the onset and progression of AD. METHODS: In this study, we investigated therapeutic and preventive effect of prebiotics, including ß-glucan and inulin, using an oxazolone (OX)-induced AD-like mouse model. Prebiotics were orally administered 2 weeks after the end of sensitization period (therapeutic study) and 3 weeks before the initial sensitization (prevention study). The physiological and histological alterations in the skin and gut of the mice were investigated. RESULTS: In the therapeutic study, the severity of skin lesions and inflammatory responses were effectively reduced after administering ß-glucan and inulin, respectively. The expression level of calprotectin was significantly decreased by approximately 2-fold (P < 0.05) in the skin and gut of prebiotics-treated mice compared to the control. In addition, epidermal thickness and the number of infiltrated immune cells were markedly reduced in the dermis of prebiotics-treated mice compared with to those in the OX-induced mice (P < 0.05). These findings were same as in the prevention study. Importantly, pre-administration of ß-glucan and inulin prevented the progression of AD by promoting the growth of good bacteria in the gut of OX-induced AD mice. However, the co-administration of ß-glucan and inulin did not show enhanced preventive effects on these alterations. CONCLUSIONS: Prebiotics has a therapeutic effect on AD in OX-induced AD mouse model. Moreover, our study suggests that prebiotics prevents the development of AD and this effect is associated with a change in gut microbiome.

Targeting IKKß Activity to Limit Sterile Inflammation in Acetaminophen-Induced Hepatotoxicity in Mice.

The kinase activity of inhibitory κB kinase ß (IKKß) acts as a signal transducer in the activating pathway of nuclear factor-κB (NF-κB), a master regulator of inflammation and cell death in the development of numerous hepatocellular injuries. However, the importance of IKKß activity on acetaminophen (APAP)-induced hepatotoxicity remains to be defined. Here, a derivative of caffeic acid benzylamide (CABA) inhibited the kinase activity of IKKß, as did IMD-0354 and sulfasalazine which show therapeutic efficacy against inflammatory diseases through a common mechanism: inhibiting IKKß activity. To understand the importance of IKKß activity in sterile inflammation during hepatotoxicity, C57BL/6 mice were treated with CABA, IMD-0354, or sulfasalazine after APAP overdose. These small-molecule inhibitors of IKKß activity protected the APAP-challenged mice from necrotic injury around the centrilobular zone in the liver, and rescued the mice from hepatic damage-associated lethality. From a molecular perspective, IKKß inhibitors directly interrupted sterile inflammation in the Kupffer cells of APAP-challenged mice, such as damage-associated molecular pattern (DAMP)-induced activation of NF-κB activity via IKKß, and NF-κB-regulated expression of cytokines and chemokines. However, CABA did not affect the upstream pathogenic events, including oxidative stress with glutathione depletion in hepatocytes after APAP overdose. N-acetyl cysteine (NAC), the only FDA-approved antidote against APAP overdose, replenishes cellular levels of glutathione, but its limited efficacy is concerning in late-presenting patients who have already undergone oxidative stress in the liver. Taken together, we propose a novel hypothesis that chemical inhibition of IKKß activity in sterile inflammation could mitigate APAP-induced hepatotoxicity in mice, and have the potential to complement NAC treatment in APAP overdoses.

Factors Influencing Training Transfer Among Infection Control Professionals Participating in Infectious Disease Training.

INTRODUCTION: Infectious disease training is considered vital in health care systems to improve knowledge, skills, and work performance of infection control professionals. However, the extent to which trainees effectively transfer knowledge, skills, and attitudes that they acquire through training has received little attention. This study aimed to identify factors influencing training transfer of infection control professionals receiving infectious disease training. METHODS: This cross-sectional study selected infection control professionals who completed an infectious disease training program provided by Korea Human Resources Development Institute for Health and Welfare. A self-reported questionnaire was used to collect data on sociodemographic variables, trainee characteristics, training design, work environment, and training transfer. Data analysis was conducted using SPSS (version 26.0). RESULTS: The mean age of the 139 participants was 41.45 years, and 77% were female participants. Regression analysis indicated that the following factors significantly influenced the training transfer of infection control professionals and thereby decrease morbidity and mortality: for trainee characteristics, transfer experience (ß = 0.205, P = 0.012) and motivation to learn (ß = 0.196, P =0.016); for training design, learning objectives (ß = 0.269, P = 0.021), goals (ß = 0.356, P =0.023), and methods (ß = 0.365, P = 0.020); and for the work environment, supervisor support (ß = 0.275, P =0.024) and colleague support (ß = 0.474, P = 0.022). CONCLUSION: Future training programs for improving training transfer should focus more on strategies to improve the motivation for training transfer. Trainees should be guided on (1) how to apply training knowledge in specific clinical contexts to improve their performance and (2) potential methods to get support from their supervisors and colleagues during training.

Therapeutic Application of Virtual Reality in the Rehabilitation of Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.

This review aimed to quantify the effect of therapeutic application of virtual reality (VR) on cognitive function in individuals with mild cognitive impairment (MCI). We searched for randomized controlled trials involving VR in the interventions provided to individuals with MCI. After searching four international electronic databases, we analyzed six studies involving 279 individuals with MCI. RevMan 5.4 was used for quality assessment and quantitative analysis. Therapeutic application of VR in individuals with MCI resulted in a significant improvement in cognitive function (mean difference = -1.46; 95% confidence interval: -2.53 to -0.39; heterogeneity: χ2 = 970.56, df = 18, I2 = 98%; and overall effect: Z = 2.67, p = 0.008). However, there was no significant improvement in the subcategories such as global cognition, working memory, executive function, memory function, and attention. In conclusion, feedback stimulation through VR has a potential value in improving cognitive function in individuals with MCI. However, on the basis of the results of the subcategories, a personalized VR program is required for the individual subcategories of cognitive function.

Efficacy of radial extracorporeal shockwave therapy in rehabilitation following arthroscopic rotator cuff repair: A STROBE compliant study.

Rotator cuff tear is a common cause of shoulder pain and disability. Arthroscopic rotator cuff repair (ARCR) is performed to treat a torn tendon. Postoperative joint immobilization is essential, but it is a problem that needs to be addressed in the rehabilitation process. This study aimed to evaluate the effects of radial extracorporeal shock wave therapy (rESWT) in patients who underwent ARCR and required active movement after the immobilization period. This study was an open-label, prospective, single-arm trial of 30 inpatients aged >18 years who underwent ARCR. A total of 6 rESWT sessions, along with the conventional rehabilitation program for ARCR patients, were provided at the hospital's sports rehabilitation center for 2 weeks. The application sites of rESWT are periscapular muscles (supraspinatus, infraspinatus, teres minor, and rhomboid). Evaluations were conducted 3 time points-baseline, immediately after the first session of rESWT, and after 2 weeks of intervention. The outcome measures were the numeric pain rating scale for pain, and shoulder flexion, scaption flexion, abduction, horizontal adduction, external rotation, and internal rotation for shoulder range of motion. For shoulder function, disabilities of the arm, shoulder and hand, shoulder pain and disability index, and simple shoulder test were used, and muscle strength was expressed by grip strength. supraspinatus and infraspinatus evaluated thickness, tone, and stiffness. The muscle strength (95% CI, -3.554 to -0.073) and supraspinatus tone (P = .017) showed significant changes immediately after the first session of rESWT. Further, there was significant improvement in ROM (P < .01); shoulder function (P < .01); and muscle strength (95% CI, -3.561 to -0.625), supraspinatus stiffness (95% CI, -67.455 to -26.345), and infraspinatus stiffness (P = .045) after 2 weeks of intervention. However, muscle thickness and tone were significantly improved only in supraspinatus (P = .044, P = .040). Rehabilitation with radial extracorporeal shock wave therapy additionally applied to the periscapular muscles in patients who started active movement in rehabilitation after arthroscopic rotator cuff repair is effective for shoulder function and muscle properties (muscle strength, thickness, tone, and stiffness). However, a randomized controlled trial is needed to further assess the effects of radial extracorporeal shock wave therapy alone.

Glyoxalase 1 as a Therapeutic Target in Cancer and Cancer Stem Cells.

Methylglyoxal (MG) is a dicarbonyl compound formed in cells mainly by the spontaneous degradation of the triose phosphate intermediates of glycolysis. MG is a powerful precursor of advanced glycation end products, which lead to strong dicarbonyl and oxidative stress. Although divergent functions of MG have been observed depending on its concentration, MG is considered to be a potential anti-tumor factor due to its cytotoxic effects within the oncologic domain. MG detoxification is carried out by the glyoxalase system. Glyoxalase 1 (Glo1), the ubiquitous glutathione-dependent enzyme responsible for MG degradation, is considered to be a tumor promoting factor due to it catalyzing the removal of cytotoxic MG. Indeed, various cancer types exhibit increased expression and activity of Glo1 that closely correlate with tumor cell growth and metastasis. Furthermore, mounting evidence suggests that Glo1 contributes to cancer stem cell survival. In this review, we discuss the role of Glo1 in the malignant progression of cancer and its possible use as a promising therapeutic target for tumor therapy. We also summarize therapeutic outcomes of Glo1 inhibitors as prospective treatments for the prevention of cancer.

Chemical inhibition of TRAF6-TAK1 axis as therapeutic strategy of endotoxin-induced liver disease.

The liver is exposed to gut-derived bacterial endotoxin via portal circulation, and recognizes it through toll-like receptor 4 (TLR4). Endotoxin lipopolysaccharide (LPS) stimulates the self-ubiquitination of ubiquitin ligase TRAF6, which is linked to scaffold with protein kinase TAK1 for auto-phosphorylation and subsequent activation. TAK1 activity is a signal transducer in the activating pathways of transcription factors NF-κB and AP-1 for production of various cytokines. Here, we hypothesized that TRAF6-TAK1 axis would be implicated in endotoxin-induced liver disease. Following exposure to endotoxin LPS, TLR4-mediated phosphorylation of TAK1 and transcription of cell-death cytokine TNF-α were triggered in Kupffer cells but not in hepatocytes as well as TNF receptor-mediated and caspase-3-executed apoptosis was occurred in D-galactosamine (GalN)-sensitized hepatocytes under co-culture with Kupffer cells. Treatment with pyridinylmethylene benzothiophene (PMBT) improved endotoxin LPS-induced hepatocyte apoptosis in GalN-sensitized C57BL/6 mice via suppressing NF-κB- and AP-1-regulated expression of TNF-α in Kupffer cells, and rescued the mice from hepatic damage-associated bleeding and death. As a mechanism, PMBT directly inhibited Lys 63-linked ubiquitination of TRAF6, and mitigated scaffold assembly between TRAF6 and the TAK1-activator adaptors TAB1 and TAB2 complex in Kupffer cells. Thereby, PMBT interrupted TRAF6 ubiquitination-induced activation of TAK1 activity in the TLR4-mediated signal cascade leading to TNF-α production. However, PMBT did not directly affect the apoptotic activity of TNF-α on GalN-sensitized hepatocytes. Finally, we propose chemical inhibition of TRAF6-TAK1 axis in Kupffer cells as a strategy for treating liver disease due to gut-derived endotoxin or Gram-negative bacterial infection.