Establishment of a type 1 diabetes structured education programme suitable for Chinese patients: type 1 diabetes education in lifestyle and self adjustment (TELSA).

BACKGROUND: Various guidelines recommend that all adults diagnosed with type 1 diabetes (T1D) should be offered an evidence based, structured education programme (SEP) to optimize self-management care. China has a 13,000 annual increase in newly diagnosed T1D cases, of which 65% are adults. However, there is yet no validated SEP targeted to T1D patients in China. The purpose of this study is to establish a structured T1D self-management education programme-'Type 1 Diabetes Education in Lifestyle and Self Adjustment' (TELSA) that is adapted to medical and cultural practices in China. METHODS: TELSA programme was developed based on the ADDIE model, following three steps: i) Semi-structured interviews were administered to 10 healthcare professionals (HCPs) and 13 T1D patients. Different topic guides, focusing on 4 dimensions including goals, contents, format of delivery, and quality assurance, were designed for either HCPs or patients. The interviews were recorded and analysed with thematic analysis. ii) Extracted themes were modified according to Delphi consultation. iii) Preliminary courses were conducted as pilot study to evaluate the effects of TELSA and optimization of the curriculum was finalized accordingly. RESULTS: A total of 18 themes in 4 dimensions of the programme design were identified in the final version: i) goals: 'behaviour modification' and 'outcome improvement'; ii) contents: 'living with T1D', 'self-monitoring of blood glucose', 'knowing insulin', 'insulin dose adjustment', 'carbohydrates and carbohydrate counting', 'hypoglycaemia', 'complications of diabetes', 'managing psychological issues', 'physical activity', and 'question-and-answer'; iii) format: 'multidisciplinary team combined with peer support', 'face-to-face education followed by remote learning', and '2-day programme held on weekends'; and iv) quality assurance: 'after-class quiz', 'patients' feedback', and 'long-term evaluation on effectiveness'. CONCLUSIONS: A type 1 diabetes structured education programme in China was set up and shown to be applicable under local medical, social, and cultural environment. TRIAL REGISTRATION: NCT03610984. Date of registration: August 2, 2018.

Explore the variation of MMP3, JNK, p38 MAPKs, and autophagy at the early stage of osteoarthritis.

Osteoarthritis is a chronic disease characterized by cartilage degeneration and chondrocyte apoptosis. Mitogen-activated protein kinase (MAPK) signaling pathway plays a key role in regulating OA process. Autophagy has an important effect on the OA process, and it is believed to be regulated by MAPKs. To reveal the mechanism and the effect of JNK and p38 MAPKs on matrix metalloproteinase 3 (MMP3) and autophagy in OA, the study established OA model in rabbits, used the measurement of the Osteoarthritis Research Society International scoring system to evaluate OA model, and conducted general observation, histological observation, and Western blotting of JNK, phosphorylate-JNK (P-JNK), p38, phosphorylate-p38 (P-p38), MMP3, and light-chain 3 (LC3)-II/LC3-I to explore the variation of JNK, p38 MAPKs, and autophagy at the early stage of OA. With OA progressing at the early stage, MMP3, P-p38, and P-JNK were gradually upregulated from the baseline to the peak in study groups when compared with the control group; JNK and p38 variated of turbulence without statistical difference; and LC3-II/LC3-I had a decreasing tendency from the 0- to 15-day group. This study identifies that compromised autophagy may be related to the OA progress and that JNK and p38 MAPKs have positive regulation on MMP3 and negative regulation on autophagy. It also implicates a new therapeutic strategy for OA and other degenerate diseases based on selective MAPK inhibitors, reduction of MMP3, and autophagy.

A New Approach of Short Wave Protection against Middle Cerebral Artery Occlusion/Reperfusion Injury via Attenuation of Golgi Apparatus Stress by Inhibition of Downregulation of Secretory Pathway Ca(2+)-ATPase Isoform 1 in Rats.

BACKGROUND: Short wave (SW), a pattern of electromagnetic therapy, achieves an oscillating electromagnetic field. It has been reported that it may have a potential effect on cerebral injury. The present study was designed to investigate the potential role and possible mechanism of SW in focal cerebral ischemia/reperfusion (I/R) injury in rats. Secretory pathway Ca(2+)/Mn(2+) ATPase isoform 1 is a major component of Golgi apparatus stress. It has been reported as representative of Golgi apparatus stress. METHODS: Up to 120 minutes of middle cerebral artery occlusion (MCAO) and reperfusion injury was induced in male Sprague-Dawley rats. Different sessions of SW daily were administered over head after reperfusion from day 1 to day 7. Functional recovery scores, survival rates, infarct volume analysis, electron microscope test, and western blotting studies were used to analyze the therapy. RESULTS: SW protected against neuronal death and apoptosis in cornu ammon 1 region of hippocampus by reducing neuronal deficit, infarct volume, and ultrastructure. SW partly inhibited upregulation of caspase3. In addition, the expression of secretory pathway Ca(2+)-ATPase isoform 1 (SPCA1) was upregulated by SW. CONCLUSIONS: Our data indicate that SW can be protected against focal cerebral I/R injury, and the influence on Golgi apparatus stress might provide us a new perspective in further study. To the authors' knowledge, this is the first report using SW to increase expression of SPCA1 indicating modulate Golgi apparatus stress in MCAO and reperfusion model.

Muscle activation patterns and gait changes in unilateral knee osteoarthritis patients: a comparative study with healthy controls.

The objective of this study was to investigate the differences in muscle activation and kinematic parameters between patients with unilateral knee osteoarthritis (OA) and healthy individuals. Additionally, the study aimed to determine the correlation between muscle activation and kinematic parameters with knee OA symptoms. Participants with unilateral knee OA (n = 32) and healthy individuals (n = 32) completed the gait test. Electromyography (EMG) and motion capture were employed to collect muscle activation data and kinematic parameters. Spearman's correlation coefficient was used to analysis the correlation between BMI, symptomatic side EMG parameters, kinematic parameters, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Furthermore, a multiple linear regression analysis of WOMAC pain was also conducted. The peak root mean square, integrated electromyography, and co-activation index (CCI) were increased bilaterally in the unilateral knee OA group compared to the healthy group. Furthermore, these values were higher on the symptomatic side than on the asymptomatic side. Compared with the healthy group, the knee OA group had lower gait speed, decreased stride length and cadence on bilateral sides, longer total stance time and double-stance time, and shorter single stance time and swing time. The maximum knee flexion angle of the swing phase on the symptomatic side of the knee OA group was smaller than that on the asymptomatic side and healthy group. Changes in EMG and gait parameters on the symptomatic side correlated with WOMAC scores. The main factors influencing WOMAC pain were the CCI values of the lateral femoral and biceps femoris muscles and gait speed. Muscle activation and kinematic parameters in the lower limbs of patients with unilateral knee OA were altered bilaterally during walking. These alterations on the symptomatic side were associated with knee OA-related pain. ChiCTR2200064958. Date of registration: 2022-10-24. Key Points • Unilateral symptomatic knee OA leads to bilateral alterations in muscle activation and gait parameters. • Symptomatic muscle activation and gait parameter changes in knee OA patients are associated with knee OA symptoms. • Correcting abnormal muscle activation conditions and gait training may reduce knee OA-related pain.

Exosomal miR-150 derived from BMSCs inhibits TNF-α-mediated osteoblast apoptosis in osteonecrosis of the femoral head by GREM1/NF-κB signaling.

Aim: The purpose of this study was to investigate the functions of exosomal miR-150 derived from bone marrow mesenchymal stem cells in osteonecrosis of the femoral head (ONFH). Materials & methods: Cell viability and apoptosis were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. Alizarin red staining was performed to detect calcium deposits. A rat model was established to assess the effects of exosomal miR-150 on ONFH in vivo. Results: Exosomes or exosomal miR-150 derived from bone marrow mesenchymal stem cells inhibited TNF-α-induced osteoblast apoptosis and promoted osteogenic differentiation and autophagy. Exosomal miR-150 suppressed apoptosis and induced autophagy in TNF-α-treated osteoblasts by regulating the GREM1/NF-κB axis. Exosomal miR-150 also improved the pathological features of ONFH in vivo. Conclusion: Exosomal miR-150 alleviates ONFH by mediating the GREM1/NF-κB axis. This study provides a potential therapeutic strategy for ONFH.

Osteonecrosis of the femoral head (ONFH) is an orthopedic disease that frequently occurs in young adults aged less than 50 years. At present, there is no widely accepted curative surgical procedure or drug therapy for this disease. Bone marrow mesenchymal stem cells (BMSCs) play a key role in the progression of ONFH. BMSC-derived exosomes refer to small membrane vesicles that can transfer proteins, miRNAs and mRNAs, which are closely related to the development of ONFH. This study showed that exosomal miRNA-150 derived from BMSCs inhibited TNF-α-induced osteoblast apoptosis and promoted osteogenic differentiation and autophagy by regulating the GREM1/NF-κB axis. In addition, exosomal miRNA-150 alleviated the symptoms of ONFH in rats.

MAPK inhibitors protect against early­stage osteoarthritis by activating autophagy.

Osteoarthritis (OA) is a chronic, age­related osteoarthropathy that causes a considerable decline in quality of life, as well as economic losses due to its high incidence and poor prognosis. Mitogen­activated protein kinases (MAPKs) regulate multiple cellular processes, including proliferation, differentiation and apoptosis, in certain diseases, such as cancer, diabetes and Alzheimer's disease. The present study aimed to investigate the regulatory role of the MAPK signaling pathway in early­stage OA. A rabbit model of early­stage OA was induced by treatment with the enzyme papain. U0126 [an extracellular signal­regulated kinase (ERK) inhibitor], SP600125 [a Jun NH2­terminal kinase (JNK) inhibitor] and SB203580 (a p38 inhibitor) were administered to the rabbits via intra­articular injection. The severity of OA was assessed by histological examination using H&E, toluidine blue and safranin­O/fast green staining, as well by analyzing the glycosaminoglycan (GAG) content and determining the OA Research Society International (OARSI) score. Western blotting was used to detect the protein expression levels of matrix metalloproteinase­3 (MMP3), ERK, phosphorylated (p)­ERK, p38, p­p38, JNK, p­JNK, Beclin1, UNC­51­like kinase 1 (ULK1) and microtubule­associated protein 1 light chain 3 (LC3)II/I. U0126, SP600125 or SB203580 treatment significantly decreased the OARSI scores and significantly increased the GAG levels in the cartilaginous tissues of OA model rabbits. These results indicated that the MAPK inhibitors reduced the severity of OA­induced injury at the early stage. Western blotting results demonstrated that MAPK inhibition significantly decreased the protein expression levels of MMP3 in OA cartilage. The protective effect of MAPK inhibitors in OA was mediated via the activation of autophagy, as demonstrated by the increased protein expression levels of LC3II/I, ULK1 and Beclin1. Overall, the data indicated that MAPK inhibitors may exert a protective effect against OA by restoring compromised autophagy. Furthermore, the present study suggested that MAPK inhibitors may represent a potential pharmacological strategy for treating OA in the future.

Genetic ablation of TAZ induces HepG2 liver cancer cell apoptosis through activating the CaMKII/MIEF1 signaling pathway.

BACKGROUND AND OBJECTIVE: Transcriptional coactivator with PDZ-binding motif (TAZ) has been found to be associated with tumor progression. Mitochondrial homeostasis regulates cancer cell viability and metastasis. However, the roles of TAZ and mitochondrial homeostasis in liver cancer viability have not been explored. The aim of our study was to investigate the influence of TAZ on HepG2 liver cancer cell apoptosis. MATERIALS AND METHODS: HepG2 liver cancer cell was used in the present study, and shRNA against TAZ was transfected into HepG2 cell to knockdown TAZ expression. Mitochondrial function was analyzed using Western blotting, immunofluorescence assay, and flow cytometry. Pathway blocker was used to confirm the role of CaMKII pathway in TAZ-mediated cancer cell death. RESULTS: Our results indicated that TAZ deletion induced death in HepG2 cell via apoptosis. Biological analysis demonstrated that mitochondrial stress, including mitochondrial bioenergetics disorder, mitochondrial oxidative stress, and mitochondrial apoptosis, were activated by TAZ deletion. Furthermore, we found that TAZ affected mitochondrial stress by triggering mitochondrial elongation factor 1 (MIEF1)-related mitochondrial dysfunction. The loss of MIEF1 sustained mitochondrial function and promoted cancer cell survival. Molecular investigation illustrated that TAZ regulated MIEF1 expression via the CaMKII signaling pathway. Blockade of the CaMKII pathway prevented TAZ-mediated MIEF1 upregulation and improved cancer cell survival. CONCLUSION: Taken together, our results highlight the key role of TAZ as a master regulator of HepG2 liver cancer cell viability via the modulation of MIEF1-related mitochondrial stress and the CaMKII signaling pathway. These findings define TAZ and MIEF1-related mitochondrial dysfunction as tumor suppressors that act by promoting cancer apoptosis via the CaMKII signaling pathway, with potential implications for new approaches to liver cancer therapy.

Identification and Analysis of Blood Gene Expression Signature for Osteoarthritis With Advanced Feature Selection Methods.

Osteoarthritis (OA) is a complex disease that affects articular joints and may cause disability. The incidence of OA is extremely high. Most elderly people have the symptoms of osteoarthritis. The physiotherapy of OA is time consuming, and the chances of full recovery from OA are very minimal. The most effective way of fighting OA is early diagnosis and early intervention. Liquid biopsy has become a popular noninvasive test. To find the blood gene expression signature for OA, we reanalyzed the publicly available blood gene expression profiles of 106 patients with OA and 33 control samples using an automatic computational pipeline based on advanced feature selection methods. Finally, a compact 23-gene set was identified. On the basis of these 23 genes, we constructed a Support Vector Machine (SVM) classifier and evaluated it with leave-one-out cross-validation. Its sensitivity (Sn), specificity (Sp), accuracy (ACC), and Mathew's correlation coefficient (MCC) were 0.991, 0.909, 0.971, and 0.920, respectively. Obviously, the performance needed to be validated in an independent large dataset, but the in-depth biological analysis of the 23 biomarkers showed great promise and suggested that mRNA surveillance pathway and multicellular organism growth played important roles in OA. Our results shed light on OA diagnosis through liquid biopsy.

Clinical application of ICF key codes to evaluate patients with dysphagia following stroke.

This study was aimed to identify and evaluate the International Classification of Functioning (ICF) key codes for dysphagia in stroke patients. Thirty patients with dysphagia after stroke were enrolled in our study. To evaluate the ICF dysphagia scale, 6 scales were used as comparisons, namely the Barthel Index (BI), Repetitive Saliva Swallowing Test (RSST), Kubota Water Swallowing Test (KWST), Frenchay Dysarthria Assessment, Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). Multiple regression analysis was performed to quantitate the relationship between the ICF scale and the other 7 scales. In addition, 60 ICF scales were analyzed by the least absolute shrinkage and selection operator (LASSO) method. A total of 21 ICF codes were identified, which were closely related with the other scales. These included 13 codes from Body Function, 1 from Body Structure, 3 from Activities and Participation, and 4 from Environmental Factors. A topographic network map with 30 ICF key codes was also generated to visualize their relationships. The number of ICF codes identified is in line with other well-established evaluation methods. The network topographic map generated here could be used as an instruction tool in future evaluations. We also found that attention functions and biting were critical codes of these scales, and could be used as treatment targets.

Secretory pathway Ca(2+)-ATPase isoform 1 knockdown promotes Golgi apparatus stress injury in a mouse model of focal cerebral ischemia-reperfusion: In vivo and in vitro study.

The present study was designed to investigate the potential role of secretory pathway Ca(2+)-ATPase isoform 1(SPCA1) in experimental focal cerebral ischemia-reperfusion injury. Cerebral ischemia-reperfusion was induced by transient middle cerebral artery occlusion (MCAO) for 2h s in Sprague-Dawley rats, and then the expression levels of SPAC1 mRNA and protein were determined. Results showed that SPCA1 level was transiently increased 1 day after reperfusion in peri-infarction area, while markedly increased in infarction core on 3day and 7 day after reperfusion. Then a SPCA1 lentivirus was used to achieve knockdown of SPCA1 gene: Ca(2+) transporting type 2C, member 1 (ATP2C1) gene. It has been observed that SPCA1 knockdown by lentivirus markedly increased cerebral infarction volume in vivo. Meanwhile, SPCA1 knockdown also facilitated per-oxidative production, including nitric oxide (NO) and 3-nitrotyrosine (3-NT) and decreased the expression of total superoxide dismutase (SOD) and manganese superoxide dismutase (MnSOD). Moreover, in vitro study showed that SPCA1 knockdown increased hydrogen peroxide (H2O2)-induced lactate dehydrogenase (LDH) leakage dose-dependently, and elevated caspase3 level in neuro-2a (N2a) cells. In addition, SPCA1 knockdown increased H2O2-induced production of nitric oxide and 3-NT dose-dependently, and reversed the increased activity of total SOD and MnSOD in neuro-2a cells. In conclusion, the present study indicated that SPCA1 could suppress over active Golgi apparatus (GA) stress thus attenuate cerebral ischemia-reperfusion injury.