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1.
Int Immunopharmacol ; 126: 111253, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38007850

RESUMO

OBJECTIVE: Diabetic nephropathy (DN) is the main cause of end-stage renal disease, and there are no targeted treatment options at present. The efficacy of the new immunosuppressive drug (5R)-5-hydroxytriptolide (LLDT8) in improving kidney inflammation has been demonstrated in multiple studies. The present study was intended to investigate the preventive and therapeutic effects of LLDT8 on DN and to reveal its potential pharmacological mechanisms. METHODS: The effects of LLDT8 on liver and kidney functions, and urine microprotein of Streptozotocin (STZ) induced DN mice were detected. The protective effect of LLDT8 on the kidney tissue was observed by pathological staining and transmission electron microscopy. Cell culture experiments were performed to detect the effects of LLDT8 on the expression of chemokines and epithelial-mesenchymal transition (EMT) in high glucose-induced TCMK1 cells using real-time polymerase chain reaction (RT-PCR) and western blot (WB) techniques and to detect the influence of LLDT8 on the secretion of pro-inflammatory and pro-fibrotic factors in high glucose-induced RAW264.7 cells. RESULTS: In animal experiments, treatment with high-dose LLDT8 (0.25 mg/kg/2d) reduced 24 h urinary albumin excretion, improved structural kidney damage, and delayed fibrosis progression in DN mice. Immunofluorescence results showed that LLDT8 intervention reduced macrophage infiltration in kidney tissues of DN mice. PCR and WB results of kidney tissues showed reduced expressions of chemokines CCL2 and M-CSF1 in the LLDT8 intervention group compared to the DN group. In cellular assays, LLDT8 treatment reduced chemokine secretion in high glucose-induced TCMK1 cells, but had no effect on EMT of TCMK1 cells. LLDT8 treatment reduced the secretion of pro-inflammatory and pro-fibrotic factors in high glucose-induced RAW264.7 cells. CONCLUSIONS: The present study suggests that LLDT8 could effectively inhibit the secretion of pro-inflammatory and pro-fibrotic factors by macrophages, which could alleviate high glucose-induced renal tissue injury and slow down the process of tissue fibrosis and DN.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Camundongos , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Rim/patologia , Glucose/metabolismo , Macrófagos , Fibrose
2.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-995887

RESUMO

Objective:To investigate the clinical outcomes of homodigital reversed dorsal digital artery island flap innervated by the dorsal digital nerve to repair degloving injury of distal thumb.Methods:From July 2016 to June 2019, a total of 15 cases (15 thumbs) with degloving injury of distal part were admitted to the Department of Hand Surgery, the Second Hospital of Tangshan. Nine males and six females were involved, with an average age of 49 years (range, 41 to 69 years). There were twist injury in eight cases and crush injury in seven cases, with four cases of distal phalanx fracture. The defect dimensions after debridement ranged from 3.5 cm×1.8 cm to 4.6 cm×2.4 cm, and the dimension of the flaps ranged from 3.8 cm×2.1 cm to 5.0 cm×2.7 cm. All defects were repaired using homodigital reversed dorsal digital artery island flap innervated by the dorsal digital nerve. The survival, appearance and sensory recovery of the flaps and function of the injured fingers were observed at the follow-up after operation.Results:All the flaps survived without wound infection and blood supply disorder. The follow-up times ranged from 9 to 22 months (mean, 16 months). There was satisfactory appearance of the flaps with similar color and texture to the surrounding tissue. Fracture healing ranged from 4 to 6 weeks. At final follow-up, the values of static 2-PD test of the flaps ranged from 5 to 10 mm (mean, 7.8 mm). The results of range of motion of injured thumb joints were excellent in nine cases and good in five cases. There was slight linear scar left at the donor area of dorsal thumb.Conclusions:The innervated reversed dorsal digital artery island flap has a simple procedure and minimal donor-site cost, which is especially suitable for elderly patients who refuse to free toe transfers.

3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-873585

RESUMO

@#The objectives of the study were to screen prostaglandin E2 receptor 4 antagonist from active compounds of Baeckea frutescens L. and to explore its anti-rheumatoid arthritis effect.The HEK293T-EP4 cell antagonist screening model was established in vitro. Homogeneous time-resolved fluorescence (HTRF) technique was used to screen the active compounds of Baeckea frutescens L..SPF grade ICR male mice were randomly divided into control group, model group, methotrexate group, and Baeckea frutescens L.compound BF-2 (100, 50 and 25 mg/kg) groups. The collagen-induced arthritis (CIA) mouse model was established in vivo. The swelling volume of the toes of mice was measured, and the pathological examination was analyzed by staining with hematoxylin and eosin.SPF grade ICR mice, male, were randomly divided into control group, BF-2 (100, 50 and 25 mg/kg) group, and aspirin group.The acetic acid-induced body writhing test was observed.The EP4 in vitro antagonist screening model was successfully established.The preliminary screening results found that BF-2, BF-20, BF-11 and BF-12 had strong EP4 antagonistic activity [(102.11 ± 3.45)%, (90.31 ± 3.59)%, (75.72 ± 1.79)% and (76.84 ± 1.64)%], and BF-2 had the strongest antagonistic activity (IC50 = 0.99 ± 0.08 μg/mL).BF-2 could significantly inhibit the toe swelling of CIA mice, and relieve the degradation of articular cartilage matrix and inflammatory cell infiltration.At the same time, compared with the control group, the writhing times of the mice in each dose of BF-2 were significantly reduced.In this study, BF-2 of Baeckea frutescens L.was selected as an EP4 antagonist, which has potential anti-rheumatoid arthritis activity.

4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-523092

RESUMO

With the development of science and technology,cosmetic tooth medical science becomes a new developing subject.This article discusses the professional qualities needed as a cosmetic tooth doctor,the pschological characteristics of patients and its corresponding countermeasures from the point of view of medical ethics to obtain satisfactory result for both doctor and patient.

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