The global prevalence of diabetes mellitus (DM) and its complications has been showing an upward trend in the past few decades, posing an increased economic burden to society and a serious threat to human life and health. Therefore, it is urgent to investigate the effectiveness of complementary and alternative therapies for DM and its complications. Luteolin is a kind of polyphenol flavonoid with widely existence in some natural resources, as a safe dietary supplement, it has been widely studied and reported in the treatment of DM and its complications. This review demonstrates the therapeutic potential of luteolin in DM and its complications, and elucidates the action mode of luteolin at the molecular level. It is characterized by anti-inflammatory, antioxidant, and neuroprotective effects. In detail, luteolin can not only improve endothelial function, insulin resistance and β-cell dysfunction, but also inhibit the activities of dipeptidyl peptidase-4 and α-glucosidase. However, due to the low water solubility and oral bioavailability of luteolin, its application in the medical field is limited. Therefore, great importance should be attached to the joint application of luteolin with current advanced science and technology. And more high-quality human clinical studies are needed to clarify the effects of luteolin on DM patients.
Humans ; Luteolin/pharmacology* ; Diabetes Mellitus/drug therapy* ; Diabetes Complications/drug therapy* ; Animals ; Antioxidants/therapeutic use*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

Humans ; Myocardial Reperfusion Injury/genetics* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac ; Apoptosis ; Myocardial Ischemia

Objective:To explore the clinical effect on reconstruction of the soft tissue defects after resection of mucous cysts of distal interphalangeal joint (DIP) with transfer of the flap of dorsal branch of proper palmar digital artery.Methods:From September 2021 to September 2023, 8 patients (8 digits) with mucous cysts on DIP were treated in the Department of Hand and Microsurgery, the Affiliated Hospital of Binzhou Medical University. All 8 cases were females, aged 55-65 years old, with an average age of 60 years old. The cyst was located in the thumb in 1 case, in the index finger in 3 cases, in the middle finger in 3 cases, and in the ring finger in 1 case. After extensive resection of the mucous cysts, the size of soft tissue defects was at 0.8 cm×0.6 cm-1.7 cm×0.9 cm. Pedicled with the dorsal branch of proper palmar digital artery, the flaps adjacent to the defects were designed to cover the wounds. The size of the flaps was 1.2 cm×1.0 cm-2.0 cm×1.2 cm. Donor sites of the flap were covered by the full thickness skin grafts of medial upper arm. The postoperative follow-up was conducted by the combination of outpatient revisits and telephone reviews to observe the survival of the flap, and the functional recovery was evaluated according to the Evaluation Standard of Upper Limb Functional of Hand Surgery of Chinese Medical Association.Results:All flaps survived well after surgery. Postoperative follow-up ranged from 4 to 12 months, with a mean of 10 months. At the final follow-up, there was no recurrence of mucous cyst and all symptoms disappeared. All flaps healed well, with good appearance, soft texture and without obvious difference in colour from the surrounding skin. All skin grafts healed in one stage. The range of motion of the affected DIP was 0°-70°, and the TPD was at 7-8 mm, both caused no impact on daily life. The outcomes were excellent according to the evaluation criteria set by the Evaluation Standard of Upper Limb Functional of Hand Surgery of Chinese Medical Association.Conclusion:The flap pedicled with dorsal branch of proper palmar digital artery has obvious advantages with less damage and simple operation in the treatment of a mucous cyst of DIP. It is an ideal surgical procedure.

Humans ; Myocardial Reperfusion Injury/genetics* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac ; Apoptosis ; Myocardial Ischemia

Osteoporosis can be induced by various factors including prolonged glucocorticoid usage, diminished estrogen levels, secondary hyperparathyroidism, and alterations in the microenvironment of bone tissue. The bone metabolism imbalance(osteogenic-lipogenic imbalance) plays a crucial role in the development of osteoporosis. This imbalance is primarily driven by an increase in the differentiation of bone marrow mesenchymal stem cells into adipocytes and a decrease in their differentiation into osteoblasts, thus forming the core of the osteogenic-lipogenic imbalance observed in osteoporosis. The bone morphogenesis protein(BMP) plays a crucial role in the regulation of the osteogenic-lipid balance in osteoporosis. This regulatory function is accomplished through both the Smad-dependent and Smad-independent pathways. This review centers on the Smad-dependent and Smad-independent pathways facilitated by BMP, offering a comprehensive overview of the potential mechanisms through which BMP-2, 4, 6, 7, and 9 contribute to the regulation of osteogenesis and lipid metabolism in osteoporosis via these pathways. In order to present novel insights for the identification of efficacious targets for clinical anti-osteoporosis medications.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Aim To investigate the mechanism of icar-itin(ICT)on D-galactose(D-gal)-induced TM4 ser-toli cell junctional function damage in vitro.Methods TM4 cells were divided into the normal control group and D-gal treatment group with different concentra-tions.The expression changes of TM 4 cell junction function-related proteins(ZO-1,Occludin,β-catenin and Cx43)and ERα/FAK signaling pathway-related proteins(ERα,FAK and pY397-FAK)were detected by Western blot.The concentration of ICT was screened by MTT method.TM4 cells were divided into normal control group,D-gal treatment group,and D-gal treatment+different concentrations of ICT group.The expression levels of the above proteins were detected by Western blot.Molecular docking was used to study the interaction between ERα and ICT,meanwhile predict the affinity between them.Finally,TM4 cells were di-vided into normal control group,D-gal treatment group,ERα inhibitor group,D-gal+ICT group,and ERα inhibitor+ICT group.The expression levels of the above proteins were detected by Western blot.Re-sults Compared with the normal control group,the ex-pression of junctional function-related proteins(ZO-1,Occludin,β-catenin and Cx43)and ERα/FAK signa-ling pathway-related proteins(ERα,FAK and pY397-FAK)were significantly down-regulated.After treat-ment with ICT,the expression of above proteins were significantly up-regulated.The docking results of ERα and ICT molecules revealed the formation of two hydro-gen bonds between Asp351 amino acid residue of ERα and ICT,with bond distances measuring 3.4? and 2.4?.Additionally,the docking binding energy be-tween them was found to be lower than-7 kcal·mol-1.After TM4 cells were treated with ERα inhibi-tor,the expression of above proteins and ERα/FAK signaling pathway-related proteins were significantly down-regulated,while the expression levels of the a-bove proteins did not change significantly after being given ICT protected group.Conclusions D-gal can cause damage to the junctional function of TM4 cells,and ICT can improve this damage,which may be related to the up-regulation of ERα/FAK signaling pathway.