Therapeutic Effect Of Combined Use Research Articles

Therapeutic effect and mechanism of combined use of FGF21 and insulin on diabetic nephropathy

Although FGF21 ameliorates diabetic nephropathy (DN), the efficacy is not satisfactory. Studies demonstrate that FGF21 combined with Insulin exhibits reciprocal sensitization on glucose and lipid metabolism in mice with type 2 diabetes. However, therapeutic effect of combined use of FGF21 and Insulin on DN has not been reported. Therefore, this study explored therapeutic effect and mechanism of combined use of FGF21 and Insulin on DN. Our results showed that compared with Insulin or FGF21 alone, FGF21 combined with Insulin further ameliorated blood glucose, HbAlc, OGTT, renal function, liver function, blood lipid, histopathological changes, oxidative stress and AGEs in the mice of DN (BKS-Leprem2Cd479/Gpt). Moreover, FGF21 combined with Insulin further reduced expressions of IL-1β, IL-6, TNF-α via promoting M1 type macrophage into M2 type macrophage. Results of real-time PCR and Western blot showed that FGF21 combined with Insulin upregulated the expressions of autophagy related genes LC3-Ⅱ and BCL-1. Mesangial cells play an important role in the pathological changes of DN mice. However, the effect of FGF21 on mesangial cells has not been reported. In this study, d-glucose was used in high glucose (HG) model in mesangial cells. The results showed that FGF21 significantly reduced the levels of OS, AGEs and cell overproliferation. Meanwhile, FGF21 significantly ameliorated autophagy level via upregulating the phosphorylation of AMPK and downregulating phosphorylation of mTOR. These effects were reversed in siRNA-β-klotho transfected mesangial cells. In conclusion, our results demonstrate that combination FGF21 with Insulin exhibits a better therapeutic effect on DN compared with FGF21 or Insulin alone. This study provides a theoretical basis for combined used of FGF21 and Insulin as a new treatment for DN and further provides theoretical support for application of FGF21 in treatment of DN.

Therapeutic effect of an anti-human-TNF-alpha antibody and itraconazole on feline infectious peritonitis.

Feline infectious peritonitis (FIP) is a fatal disease in wild and domestic cat species. Although several drugs are expected to be useful as treatments for FIP, no drugs are available in clinical practice. In this study, we evaluated the therapeutic effect of combined use of adalimumab (an anti-human-TNF-alpha monoclonal antibody, ADA) and itraconazole (ICZ), which are presently available to veterinarians. The neutralizing activity of ADA against fTNF-alpha-induced cytotoxicity was measured in WEHI-164 cells. Ten specific pathogen-free (SPF) cats were inoculated intraperitoneally with type I FIPV KU-2. To the cats that developed FIP, ADA (10 mg/animal) was administered twice between day 0 and day 4 after the start of treatment. ICZ (50 mg/head, SID) was orally administered daily from day 0 after the start of treatment. ADA demonstrated dose-dependent neutralizing activity against rfTNF-alpha. In an animal experiment, 2 of 3 cats showed improvements in FIP clinical symptoms and blood chemistry test results, an increase in the peripheral blood lymphocyte count, and a decrease in the plasma alpha 1-AGP level were observed after the beginning of treatment. One of the cats failed to respond to treatment and was euthanized, although the viral gene level in ascites temporarily decreased after the start of treatment. ADA was found to have neutralizing activity against rfTNF-alpha. The combined use of ADA and ICZ showed a therapeutic effect for experimentally induced FIP. We consider these drugs to be a treatment option until effective anti-FIPV drugs become available.

Therapeutic effect of combined use of interferon alpha-1b, interleukin-2 and thalidomide on reversing minimal residual disease in acute myeloid leukemia

目的探讨干扰素α-1b、白细胞介素2联合沙利度胺（“干白沙”方案）对急性髓系白血病（AML）患者微小残留病（MRD）的影响。方法对2016年7月至2018年6月收治的18例（17例来自郑州大学附属肿瘤医院，1例来自平顶山市第一人民医院）处于血液学完全缓解但MRD阳性的AML患者应用不同剂量的“干白沙”方案，监测其MRD水平变化。结果18例患者接受常规剂量“干白沙”方案1~2个月，7例患者MRD转阴，3例患者MRD水平明显下降，3例MRD水平升高，5例复发。MRD水平升高的3例患者接受加量的“干白沙”方案，2例MRD转阴，1例MRD水平下降。“干白沙”方案干预治疗MRD阳性AML总有效率为72.2%。根据治疗前MRD水平分组，MRD≥1.0%的患者有效率为57.1%（4/7），MRD<1.0%的患者有效率为81.8%（9/11）。结论“干白沙”方案可使血液学完全缓解但MRD阳性的AML患者MRD转阴或下降，增加方案药物剂量后疗效增加，疗效与治疗前MRD水平可能呈负相关。

Therapeutic effect of combined use of FGF1-loaded nano-liposomes and ultrasound-targeted microbubble destruction technique on treating rats with experimental diabetic cardiomyopathy

Objective: The therapeutic effect of acid fibroblast growth factor 1(FGF1) on rats with diabetic cardiomyopathy (DCM) was evaluated by using nano-liposomes combined with ultrasound-targeted microbubble destruction technique (UTMD). Methods: The FGF1-loaded nano-liposomes were prepared by water-in-water emulsion method combined with lyophilization technique.TypeⅠdiabetes model was induced by intraperitoneal injection of streptozotocin (STZ, 70 mg/kg) in 60 male SD rats.Sixteen weeks later, diabetic rats were randomly divided into: placebo group (saline treatment), FGF1 group, FGF1-loaded nano-liposomes group, and FGF1-loaded nano-liposomes plus UTMD group (n=15 each). After two weeks of intervention followed by 2 weeks intervention stop, all rats underwent cardiac catheterization, and the left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP) and the maximal increase/decrease rate of left ventricular pressure (LV±dp/dtmax) were measured.Then, the rats were sacrificed and myocardial tissue were obtained for Masson trichrome staining, TUNEL apoptotic staining and CD31 immunohistochemistry staining to quantify myocardial collagen fraction (CVF), cardiac myocyte apoptotic index and myocardial microvascular density (MVD). Results: (1)Scanning electron microscope results revealed good morphology and FGF1 encapsulation efficiency (84.3±2.8)% with high stability and dispensability of FGF1 loaded nano-liposomes.(2)The hemodynamic evaluation showed that LVESP, LV + dp/dt(max) and LV -dp/dt(max) were all significantly higher, while LVEDP was significantly lower in the FGF1-loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group(all P<0.05). (3)The Masson trichrome staining demonstrated that CVF was significantly higher in all DCM groups than in control group and was significantly lower in the FGF1-loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group (all P<0.05). (4)The CD31 immunohistochemical staining results showed that MVD was significantly lower in all DCM groups than in control group and was significantly higher in the FGF1-loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group (all P<0.05). (5)The TUNEL results showed that apoptotic index was significantly higher in all DCM groups than in control group and was significantly lower in the FGF1-loaded nano-liposome + UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group (all P<0.05). Conclusion: FGF1 nano-liposomes combining with UTMD technique can significantly improve cardiac functions and attenuate myocardial CVF and apoptosis and enhance myocardial MVD in DCM rats.

Effect of continuous combined therapy with vitamin K 2 and vitamin D 3 on bone mineral density and coagulofibrinolysis function in postmenopausal women

Objectives: To investigate the therapeutic effect of combined use of vitamin K 2 and D 3 on vertebral bone mineral density in postmenopausal women with osteopenia and osteoporosis. Subjects and methods: We enrolled 172 women with vertebral bone mineral density <0.98 g/cm 2 (osteopenia and osteoporosis) as measured by dual-energy X-ray absorptiometry. In this study, we employed the criteria for diagnosis of osteopenia and osteoporosis using dual energy X-ray absorptiometry proposed by the Japan Society of Bone Metabolism in 1996. Subjects were randomized into four groups (each having 43 subjects in vitamin K 2 therapy group, vitamin D 3 therapy group, vitamin K 2 and D 3 combined therapy group, or a control group receiving dietary therapy alone) and treated with respective agents for 2 years, with bone mineral density was measured prior to therapy and after 6, 12, 18, and 24 months of treatment. The bone metabolism markers analyzed were serum type 1 collagen carboxyterminal propeptide (P1CP), serum intact osteocalcin, and urinary pyridinoline. Tests of blood coagulation function consisted of measurement of activated partial thromboplastin time (APTT) and analysis of concentrations of antithrombin III (AT III), fibrinogen, and plasminogen. Results: Combined therapy with vitamin K 2 and D 3 for 24 months markedly increased bone mineral density (4.92±7.89%), while vitamin K 2 alone increased it only 0.135±5.44%. The bone markers measured, revealed stimulation of both bone formation and resorption activity. We observed an increase in coagulation and fibrinolytic activity that was within the normal range, suggesting that balance was maintained in the fibrinolysis–coagulation system. Conclusions: Continuous combination therapy with vitamin K 2 and D 3 may be useful for increasing vertebral bone mass in postmenopausal women. Furthermore, the increase in coagulation function observed during this therapy was within the physiological range, and no adverse reactions were observed.