The recombinant human fibroblast growth factor-18 (sprifermin) Improves Tendon-to-Bone Healing by promoting chondrogenesis In a Rat Rotator Cuff Repair Model

Background: Rotator cuff healing is improved by reconstructing the fibrocartilaginous structure of the tendon-to-bone enthesis. Fibroblast growth factor (FGF)-18 (sprifermin) is a well-known growth factor that improves articular cartilage repair via its anabolic effect. This study aimed to investigate the effect of recombinant human FGF-18 (rhFGF-18) on the chondrogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro and tendon-to-bone healing in a rat model of rotator cuff repair.
Methods: Histological and reverse transcription-quantitative real-time polymerase chain reaction analyses of chondral pellets cultured with different concentrations of rhFGF-18 were performed. Bilateral detachment and repair of the supraspinatus tendon were performed on rats. The rats were administered 0.2 mL sodium alginate (SA) hydrogel with (rhFGF-18/SA group, n = 12) or without (SA group, n = 12) 20 μg rhFGF-18 into the repaired side. The simple repair group (n = 12) served as a control. At 4 and 8 weeks post-surgery, histological analysis and biomechanical tests were performed.
Results: After chondrogenesis induction, compared with the control group, 10ng/mL rhFGF-18 increased pellets volume significantly (P = 0.002), with improved histological staining. It was noted that 10 ng/mL rhFGF-18 upregulated the mRNA expression (relative ratio to control) of aggrecan (2.59 ± 0.29, P < 0.001), SRY-box transcription factor 9 (1.88 ± 0.05, P < 0.001), and type II collagen (1.46 ± 0.18, P = 0.009). At 4 and 8 weeks post-surgery, more fibrocartilage and cartilaginous extracellular matrix was observed in rhFGF-18/SA-treated rats. The semiquantitative data from picrosirius red staining test were 31.1 ± 4.5 vs. 61.2 ± 4.1 at 4 weeks (P < 0.001) and 61.5 ± 2.8 vs. 80.5 ± 10.5 at 8 weeks (P = 0.002) (control vs. rhFGF-18/SA). Ultimate failure load (25.42 ± 3.61 N vs. 18.87 ± 2.71 N at 4 weeks and 28.63 ± 5.22 N vs. 22.15 ± 3.11 N at 8 weeks; P = 0.006 and P = 0.03, respectively) and stiffness (18.49 ± 1.38 N/mm vs. 14.48 ± 2.01 N/mm at 8 weeks, P = 0.01) were higher in the rhFGF-18/SA group than in the control group.
Conclusion: rhFGF-18 promoted chondrogenesis in the hBMSCs in vitro. rhFGF-18/SA improved tendon-to-bone healing in the rats by promoting regeneration of the fibrocartilage enthesis. rhFGF-18 (sprifermin) may be beneficial for improving tendon-to-bone healing after rotator cuff repair.

A pharmacokinetic study to comparatively evaluate the bioequivalence and safety of a humanized recombinant monoclonal antibody targeting human epidermal growth factor receptor-2 with the reference Herceptin in healthy Chinese subjects

Purpose: This study aimed to compare the safety, tolerability, pharmacokinetics (PK), and bioequivalence of a test humanized recombinant monoclonal antibody targeting human epidermal growth factor receptor-2 (HER-2) with the reference Herceptin®.
Materials and methods: The trial consisted of two parts (part I and part II). Part I was an open-label, sequential-cohort dose-escalation study, where 16 healthy subjects were either intravenously infused with QLHER2 (test) at single doses escalating from 0.2 to 6 mg/kg (0.2, 1, 2, 4, and 6 mg/kg) or given 4 mg/kg Herceptin (reference) for evaluating the safety, tolerability, and PK of QLHER2. Part II was a randomized, double-blind, parallel-group study to evaluate the bioequivalence of QLHER2 and Herceptin in 60 subjects.
Results: Following a 1.5-h intravenous infusion of single ascending doses of QLHER2 (1, 2, 4, or 6 mg/kg) in part I, Cmax and Tmax were 19.43-120.01 μg/mL and 68.91-157.87 h, respectively. AUC0-t and CL were 1.91-34.21 h·μg/mL and 0.54-0.12 mL/h/kg, indicating lower clearance at higher doses, with a greater than proportional increase in AUC0-t and t1/2 of 68.91-157.87 h. In part II, serum concentrations were comparable between QLHER2 and Herceptin over a 70-day sampling period, and the QLHER2/Herceptin ratios of Cmax and AUC0-t were 105.90% [90% confidence interval (CI): 95.69%-117.26%] and 95.79% (90% CI: 87.74%-106.40%), respectively.
Conclusion: The 90% CI value of Cmax and AUC0-t for QLHER2/Herceptin ratio ranged between 80.0%-125.00%, indicating that QLHER2 was bioequivalent to Herceptin. These results support further evaluation of QLHER2. Trial registration number: ChiCTR2000041577 and ChiCTR2100041802. Date of registration: 30th December, 2020 and 5th January 2021.

Recombinant Apyrase (AZD3366) Against Myocardial Reperfusion Injury

Purpose: Recombinant apyrase (AZD3366) increases adenosine production and ticagrelor inhibits adenosine reuptake. We investigated whether intravenous AZD3366 before reperfusion reduces myocardial infarct size (IS) and whether AZD3366 and ticagrelor have additive effects.
Methods: Sprague-Dawley rats underwent 30 min ischemia. At 25 min of ischemia, animals received intravenous AZD3366 or vehicle. Additional animals received intravenous CGS15943 (an adenosine receptor blocker) or intraperitoneal ticagrelor. At 24 h reperfusion, IS was assessed by triphenyltetrazolium chloride. Other rats were subjected to 30 min ischemia followed by 1 h or 24 h reperfusion. Myocardial samples were assessed for adenosine levels, RT-PCR, and immunoblotting.
Results: AZD3366 and ticagrelor reduced IS. The protective effect was blocked by CGS15943. The effect of AZD3366 + ticagrelor was significantly greater than AZD3366. One hour after infarction, myocardial adenosine levels significantly increased with AZD3366, but not with ticagrelor. In contrast, 24 h after infarction, adenosine levels were equally increased by AZD3366 and ticagrelor, and levels were higher in the AZD3366 + ticagrelor group. One hour after reperfusion, AZD3366 and ticagrelor equally attenuated the increase in interleukin-15 (an early inflammatory marker after ischemic cell death) levels, and their combined effects were additive. AZD3366, but not ticagrelor, significantly attenuated the increase in RIP1, RIP3, and P-MLKL (markers of necroptosis) 1 h after reperfusion. AZD3366, but not ticagrelor, significantly attenuated the increase in IL-6 and GSDMD-N (markers of pyroptosis) 1 h after reperfusion. At 24 h of reperfusion, both agents equally attenuated the increase in these markers, and their effects were additive.
Conclusions: AZD3366 attenuated inflammation, necrosis, necroptosis, and pyroptosis and limited IS. The effects of AZD3366 and ticagrelor were additive.

Recombinant Humanp21 Recombinant Protein

92-035 ProSci 0.05 mg 821.4 EUR

TWEAK, recombinant / TNFSF12, recombinant (Human)

054-85 PHOENIX PEPTIDE 10 μg 261.36 EUR

TAGLN Recombinant Protein (Rat) (Recombinant- Tag)

RP232205 ABM 100 ug Ask for price

TAGLN2 Recombinant Protein (Rat) (Recombinant Tag)

RP232208 ABM 100 ug Ask for price

TAGLN3 Recombinant Protein (Rat) (Recombinant Tag)

RP232211 ABM 100 ug Ask for price

TAGLN3 Recombinant Protein (Rat) (Recombinant Tag)

RP232214 ABM 100 ug Ask for price

TAGAP Recombinant Protein (Human) (Recombinant- Tag)

RP030880 ABM 100 ug Ask for price

TAGLN Recombinant Protein (Human) (Recombinant- Tag)

RP030883 ABM 100 ug Ask for price

TAGLN Recombinant Protein (Human) (Recombinant- Tag)

RP030886 ABM 100 ug Ask for price

TAGAP Recombinant Protein (Human) (Recombinant- Tag)

RP043930 ABM 100 ug Ask for price

TAGAP Recombinant Protein (Mouse) (Recombinant- Tag)

RP177155 ABM 100 ug Ask for price

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RP177161 ABM 100 ug Ask for price

CTAGE1 Recombinant Protein (Human) (Recombinant- Tag)

RP008266 ABM 100 ug Ask for price

CTAGE5 Recombinant Protein (Human) (Recombinant- Tag)

RP008269 ABM 100 ug Ask for price

CTAGEP Recombinant Protein (Human) (Recombinant- Tag)

RP008275 ABM 100 ug Ask for price

TAGLN2 Recombinant Protein (Human) (Recombinant Tag)

RP030889 ABM 100 ug Ask for price

TAGLN2 Recombinant Protein (Human) (Recombinant Tag)

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CTAG1B Recombinant Protein (Human) (Recombinant- Tag)

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Homologous recombination technology generated recombinant pseudorabies virus expressing EGFP facilitates to evaluate its susceptibility to different cells and screen antiviral compounds

Pseudorabies virus (PRV) is considered as an emerging zoonotic pathogen since its isolation from a human case. Meanwhile, the disease caused by PRV infection has led huge economic losses to Chinese pig industry since 2011. In this study, we constructed a recombinant PRV stably expressing the enhanced green fluorescent protein (EGFP) by homologous recombination technology for evaluating its susceptibility to different human cell lines and screening antiviral compounds. Stably expressed EGFP by this designed rPRVHuN-EGFP virus was confirmed in the infected cells, moreover, the growth kinetics of which was similar to that of wild type strain.
Importantly, the application of this rPRV allowed us to easily verify its infectivity in all tested human cell lines, although the infection efficiencies were lower than that in PK15 cells. Meanwhile, the antiviral activities of harmine and PHA767491 were also conveniently validated in vitro, as directly reflected by the reduced EGFP signals. These results demonstrate that this recombinant PRV virus should be a useful tool for basic virology researches and antiviral agent screening.

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