Recent evidence has suggested that synovial inflammation and macrophage polarization were involved in the pathogenesis of osteoarthritis (OA). Additionally, high-molecular-weight hyaluronic acid (HMW-HA) was often used clinically to treat OA. GRP78, an endoplasmic reticulum (ER) stress chaperone, was suggested to contribute to the hyperplasia of synovial cells in OA. However, it was still unclear whether HMW-HA affected macrophage polarization through GRP78. Therefore, we aimed to identify the effect of HMW-HA in primary synovial cells and macrophage polarization and to investigate the role of GRP78 signaling. We used IL-1β to treat primary synoviocytes to mimic OA, and then treated them with HMW-HA. We also collected conditioned medium (CM) to culture THP-1 macrophages and examine the changes in the phenotype. IL-1β increased the expression of GRP78, NF-κB (p65 phosphorylation), IL-6, and PGE2 in primary synoviocytes, accompanied by an increased macrophage M1/M2 polarization. GRP78 knockdown significantly reversed the expression of IL-1β-induced GRP78-related downstream molecules and macrophage polarization. HMW-HA with GRP78 knockdown had additive effects in an IL-1β culture. Finally, the synovial fluid from OA patients revealed significantly decreased IL-6 and PGE2 levels after the HMW-HA treatment. Our study elucidated a new form of signal transduction for HMW-HA-mediated protection against synovial inflammation and macrophage polarization and highlighted the involvement of the GRP78-NF-κB signaling pathway.

The receptor tyrosine kinase Axl and its ligand growth arrest-specific protein 6 (Gas6) are involved in the diabetic vascular disease. The aim of this study was to explore the role of Gas6/Axl system in high glucose (HG)-induced endothelial dysfunction.

Study Objectives: Diabetes mellitus per se and its related therapy have been frequently associated with an increased risk of developing dementia. However, studies that explored the risk of dementia from the use of the novel oral antidiabetic medication dipeptidyl peptidase 4 inhibitor (DPP-4i) have been limited, especially in Asian populations. The present study aimed to determine the effect of DPP-4i on the subsequent risk of dementia among patients with type 2 diabetes (T2D) in Taiwan. Methods: This study utilized data from the Longitudinal Health Insurance Database between 2008 and 2015. We enrolled 2903 patients aged ≥50 years, who were on DPP-4i for a diagnosis of T2D and had no dementia. A total of 11,612 subjects were included and compared with a propensity score-matched control group who did not use DPP-4i (non-DPP-4i group). Survival analysis was performed to estimate and compare the risk of dementia—including Alzheimer’s disease, vascular dementia, and other dementia types—between the two groups. Results: Both groups had a mean age of 68 years, had a preponderance of women (61.8%), and were followed up for a mean duration of 7 years. The risk of all-cause dementia was significantly lower in the DPP-4i group than in the non-DPP-4i group (hazard ratio (HR) 0.798; 95% confidence interval (CI) 0.681–0.883; p < 0.001), with a class effect. This trend was particularly observed for vascular dementia (HR 0.575; 95% CI 0.404–0.681; p < 0.001), but not in Alzheimer’s disease (HR 0.891; 95% CI 0.712–1.265; p = 0.297). The Kaplan–Meier analysis showed that the preventive effect on dementia was positively correlated with the cumulative dose of DPP-4i. Conclusions: DPP-4i decreased the risk of dementia with a class effect, especially vascular dementia, but not in Alzheimer’s disease. Our results provide important information on the drug choice when managing patients with T2D in clinical practice.

Thyrotoxic periodic paralysis (TPP) is a fairly common manifestation of hyperthyroidism in Asian populations, with an incidence of about 1.9% in thyrotoxic patients, but it is rarely diagnosed among Caucasians and blacks in the Western world. The diagnosis often can be made on the basis of the clinical manifestations alone. Sometimes, periodic paralysis precedes hyperthyroidism or occurs in silent hyperthyroidism. As a result, physicians may easily overlook it even when life-threatening hypokalemia is present. The pathophysiology of this disorder is still not well understood. Correction of the thyrotoxic state is the definitive treatment. Potassium supplementation, propranolol, and spironolactone may be helpful both in the acute state and in preventing attacks.

Patients with diabetes are at increased risk of cancer development and osteoporosis. Metformin is an effective agent for diabetes management. Epidemiological studies have identified an association between metformin use and cancer prevention. This article outlines the potential for metformin to attenuate the rate of osteoporosis in diabetic patients with carcinoma in situ (CIS). From the National Health Insurance Research Database of Taiwan, 7827 patients with diabetes with CIS who were receiving metformin therapy were selected, along with 23,481 patients as 1:3 sex-, age- and index year-matched controls, who were not receiving metformin therapy. A Cox proportional hazard analysis was used to compare the rate of osteoporosis during an average of 15-year follow-up. Of the subjects who were enrolled, 801 (2.56%) had osteoporosis, including 168 from the metformin group (2.15%) and 633 from the without metformin group (2.70%). The metformin group presented a lower rate of osteoporosis at the end of follow-up (p = 0.009). The Cox proportional hazard regression analysis revealed a lower rate of osteoporosis for the metformin group (adjusted hazard ratio of 0.820; 95% confidence interval = 0.691–0.972, p = 0.022). Diabetic patients with CIS under metformin therapy presented lower osteoporosis rate than those who were not receiving metformin therapy.

Background: Evidence of low-dose aspirin as the primary prevention strategy for cardiovascular disease (CVD) in diabetes are unclear. This study was designed to evaluate the effect of low-dose aspirin use for the primary prevention of CVD in diabetes. Methods: We collected randomized controlled trials of low-dose aspirin for the primary prevention of CVD in adults with diabetes lasting at least 12 months from Medline, Embase, and the Cochrane Library up to 10 November 2018. Two reviewers extracted data and appraised the reporting quality according to a predetermined protocol (CRD4201811830). This review was conducted using Cochrane standards, trial sequential analysis, and the Grading of Recommendation. The primary outcomes were major adverse cardiovascular events (MACE, including non-fatal myocardial infarction, ischemia stroke, and cardiovascular death) and an incidence of major hemorrhage (major intracranial hemorrhage and major gastrointestinal bleeding). Results: In this primary prevention (number = 29,814 participants) meta-analysis, low-dose aspirin use reduced the risk of MACE by 9% and increased the risk of major hemorrhage by 24%. The benefits were only observed in subjects of age ≥ 60 years while reducing the same risk of MACE. In efficacy, it reduced the risk of stroke but not myocardial infarction. No increase in all-cause mortality or cardiovascular death was observed. Conclusions: We suggested the use of low-dose aspirin as the primary prevention strategy for CVD in diabetes, particularly in an older population. The absolute benefits were largely counterbalanced by the bleeding hazard.