Efficacy and safety of burosumab compared with conventional therapy in patients with X-linked hypophosphatemia: A systematic review.

Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We conducted a systematic review to compare the efficacy and safety of burosumab versus conventional therapy (phosphorus and calcitriol) on XLH treatment. After a comprehensive literature search on MEDLINE/PubMed and Embase, we found nine studies for inclusion in the analysis. Risk of bias was assessed, and a random-effects model was used to determine the effect size. Clinical, biochemical, and radiological parameters of disease severity before and after treatment were analyzed and expressed in standardized mean difference (SMD). Burosumab resulted in normalization of phosphate homeostasis with an increase in renal tubular phosphate reabsorption and significant resolution of skeletal lesions (change in Thacher's total rickets severity score SMD: -1.46, 95% confidence interval [CI]: -1.76 to -1.17, p < 0.001, improvement in deformities, and decline in serum alkaline phosphatase levels [SMD: 130.68, 95% CI: 125.26-136.1, p < 0.001)]. Conventional therapy led to similar improvements in all these parameters but to a lower degree. In adults, burosumab normalized phosphorus levels (SMD: 1.23, 95% CI: 0.98-1.47, p < 0.001) with resultant clinical improvement. Burosumab treatment was well tolerated, with only mild treatment-related adverse effects. The present review indicates a potential role for burosumab in improving rickets, deformities, and growth in children with XLH. Given its superior efficacy and safety profile, burosumab could be an effective therapeutic option in children. We suggest further studies comparing burosumab versus conventional therapy in children and adults with XLH.

Disturbed flow regulates protein disulfide isomerase A1 expression via microRNA-204.

Redox processes can modulate vascular pathophysiology. The endoplasmic reticulum redox chaperone protein disulfide isomerase A1 (PDIA1) is overexpressed during vascular proliferative diseases, regulating thrombus formation, endoplasmic reticulum stress adaptation, and structural remodeling. However, both protective and deleterious vascular effects have been reported for PDIA1, depending on the cell type and underlying vascular condition. Further understanding of this question is hampered by the poorly studied mechanisms underlying PDIA1 expression regulation. Here, we showed that PDIA1 mRNA and protein levels were upregulated (average 5-fold) in the intima and media/adventitia following partial carotid ligation (PCL). Our search identified that miR-204-5p and miR-211-5p (miR-204/211), two broadly conserved miRNAs, share PDIA1 as a potential target. MiR-204/211 was downregulated in vascular layers following PCL. In isolated endothelial cells, gain-of-function experiments of miR-204 with miR mimic decreased PDIA1 mRNA while having negligible effects on markers of endothelial activation/stress response. Similar effects were observed in vascular smooth muscle cells (VSMCs). Furthermore, PDIA1 downregulation by miR-204 decreased levels of the VSMC contractile differentiation markers. In addition, PDIA1 overexpression prevented VSMC dedifferentiation by miR-204. Collectively, we report a new mechanism for PDIA1 regulation through miR-204 and identify its relevance in a model of vascular disease playing a role in VSMC differentiation. This mechanism may be regulated in distinct stages of atherosclerosis and provide a potential therapeutic target.

Efficacy and safety of burosumab compared with conventional therapy in patients with X-linked hypophosphatemia: A systematic review

ABSTRACT Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We conducted a systematic review to compare the efficacy and safety of burosumab versus conventional therapy (phosphorus and calcitriol) on XLH treatment. After a comprehensive literature search on MEDLINE/PubMed and Embase, we found nine studies for inclusion in the analysis. Risk of bias was assessed, and a random-effects model was used to determine the effect size. Clinical, biochemical, and radiological parameters of disease severity before and after treatment were analyzed and expressed in standardized mean difference (SMD). Burosumab resulted in normalization of phosphate homeostasis with an increase in renal tubular phosphate reabsorption and significant resolution of skeletal lesions (change in Thacher's total rickets severity score SMD: −1.46, 95% confidence interval [CI]: −1.76 to −1.17, p < 0.001, improvement in deformities, and decline in serum alkaline phosphatase levels [SMD: 130.68, 95% CI: 125.26-136.1, p < 0.001)]. Conventional therapy led to similar improvements in all these parameters but to a lower degree. In adults, burosumab normalized phosphorus levels (SMD: 1.23, 95% CI: 0.98-1.47, p < 0.001) with resultant clinical improvement. Burosumab treatment was well tolerated, with only mild treatment-related adverse effects. The present review indicates a potential role for burosumab in improving rickets, deformities, and growth in children with XLH. Given its superior efficacy and safety profile, burosumab could be an effective therapeutic option in children. We suggest further studies comparing burosumab versus conventional therapy in children and adults with XLH.

Silver nanoparticle as an alternate to antibiotics in cattle semen during cryopreservation.

The proposed study was to determine if the silver nanoparticles can be used as potential antimicrobial agents and can replace the use of conventional antibiotics in semen without affecting the motility and fertility of semen. The silver nanoparticles prepared by chemical reduction method were confirmed by determination of the wavelength of surface plasmon resonance peak and further characterized using Zetasizer by determining their size, polydispersity index, and zeta potential. The nanoparticles were assessed for antibacterial activity and their concentration was optimized for use in semen extender for cryopreservation. Cryopreserved semen was further evaluated for seminal parameters, antioxidant parameter, and microbial load. Prepared silver NPs showed a plasmon resonance peak at 417 nm wavelength. NPs were found to possess antibacterial activity and were supplemented in semen extender @ 125 and 250 µg/ml for semen cryopreservation. There was a significant increase in pre and post-freezing motility and other seminal parameters. The microbial load of frozen-thawed semen of control and supplemented groups were well within the permissible limits. Lipid peroxidation levels were reduced in NPs supplemented groups, and reactive oxygen species (ROS) levels were significantly reduced in semen supplemented with 125 µg/ml NPs. Thus it can be conclude that silver NPs can be successfully used as a substitute for antibiotics in cattle bull semen cryopreservation with good antimicrobial activity and no adverse effects on sperm characteristics.

Characterization of plant growth-promoting, antifungal, and enzymatic properties of beneficial bacterial strains associated with pulses rhizosphere from Bundelkhand region of India.

The present study was conducted to characterize the native plant growth-promoting rhizobacteria (PGPRs) from the pulse rhizosphere of the Bundelkhand region of India. Twenty-four bacterial isolates belonging to nineteen species (B. amyloliquefaciens, B. subtilis, B. tequilensis, B. safensis, B. haynesii, E. soli, E. cloacae, A. calcoaceticus, B. valezensis, S. macrescens, P. aeruginosa, P. fluorescens, P. guariconensis, B. megaterium, C. lapagei, P. putida, K. aerogenes, B. cereus, and B. altitudinis) were categorized and evaluated for their plant growth-promoting potential, antifungal properties, and enzymatic activities to identify the most potential strain for commercialization and wider application in pulse crops. Phylogenetic identification was done on the basis of 16 s rRNA analysis. Among the 24 isolates, 12 bacterial strains were gram positive, and 12 were gram negative. Among the tested 24 isolates, IIPRAJCP-6 (Bacillus amyloliquefaciens), IIPRDSCP-1 (Bacillus subtilis), IIPRDSCP-10 (Bacillus tequilensis), IIPRRLUCP-5 (Bacillus safensis), IIPRCDCP-2 (Bacillus subtilis), IIPRAMCP-1 (Bacillus safensis), IIPRMKCP-10 (Bacillus haynesii), IIPRANPP-3 (Bacillus amyloliquefaciens), IIPRKAPP-5 (Enterobacter soli), IIPRAJCP-2 (Enterobacter cloacae), IIPRDSCP-11 (Acinetobacter calcoaceticus), IIPRDSCP-9 (Bacillus valezensis), IIPRMKCP-3 (Seratia macrescens), IIPRMKCP-1 (Pseudomonas aeruginosa), IIPRCKPP-3 (Pseudomonas fluorescens), IIPRMKCP-9 (Pseudomonas guariconensis), IIPRMKCP-8 (Bacillus megatirium), IIPRMWCP-9 (Cedecea lapagei), IIPRKUCP-10 (Pseudomonas putida), IIPRAMCP-4 (Klebsiella aerogenes), IIPRCKPP-7 (Enterobacter cloacae), IIPRAMCP-5 (Bacillus cereus), IIPRSHEP-6 (Bacillus subtilis), IIPRRSBa89 (Bacillus altitudinis) bacterial isolates, IIPRMKCP-9, IIPRAJCP-6, IIPRMKCP-10, IIPRAMCP-5, IIPRSHEP-6, and IIPRMKCP-3 showed the maximum antagonistic activity against Fusarium oxysporum f. sp. ciceris (FOC), Fusarium oxysporum f. sp. lentis (FOL), and Fusarium udum (FU) causing wilt disease of chickpea, lentil, and pigeonpea, respectively, and maximum plant growth-promoting enzyme (phosphatase), plant growth hormone (IAA), and siderophore production show promising results under greenhouse conditions. This study is the first report of bacterial diversity in the pulse-growing region of India.

Raman characterization of single-crystalline Ga0.96Mn0.04As:Zn nanowires realized by ion-implantation.

Recent progress in the realization of magnetic GaAs nanowires (NWs) doped with Mn has attracted a lot of attention due to their potential application in spintronics. In this work, we present a detailed Raman investigation of the structural properties of Zn doped GaAs (GaAs:Zn) and Mn-implanted GaAs:Zn (Ga0.96Mn0.04As:Zn) NWs. A significant broadening and redshift of the optical TO and LO phonon modes are observed for these NWs compared to as-grown undoped wires, which is attributed to strain induced by the Zn/Mn doping and to the presence of implantation-related defects. Moreover, the LO phonon modes are strongly damped, which is interpreted in terms of a strong LO phonon-plasmon coupling, induced by the free hole concentration. Moreover, we report on two new interesting Raman phonon modes (191 and 252 cm-1) observed in Mn ion-implanted NWs, which we attribute to Eg (TO) and A1g (LO) vibrational modes in a sheet layer of crystalline arsenic present on the surface of the NWs. This conclusion is supported by fitting the observed Raman shifts for the SO phonon modes to a theoretical dispersion function for a GaAs NW capped with a dielectric shell.

Reduction of steroid-induced intraocular pressure elevation in sheep by tissue plasminogen activator.

PURPOSE: To investigate whether tissue plasminogen activator (tPA) can prevent and/or reverse steroid-induced IOP elevation in an ovine model. METHODS: Three animal groups were subjected to bilateral steroid-induced IOP elevation using thrice daily topical ocular prednisolone administration. In the first group (N = 8), one eye each of two sheep was injected intravitreally with 100 µg, 200 µg, 500 µg, or 1 mg human recombinant tPA, while contralateral eyes received vehicle. In the second group (N = 2), one eye was injected intravitreally with tPA (100 µg), while contralateral eyes received vehicle containing L-arginine. In the third group (N = 4), each animal received intravitreal tPA in one eye concurrently with initiation of bilateral steroid administration. IOP was monitored for the duration of the experiment. Tissues from eyes of the third group were used to determine relative gene expression. RESULTS: In the first and second groups, IOP decreased by 9.7 (±2.8) and 9.7 (±1.6) mm Hg, respectively, 24 hours after tPA administration. In the third group, tPA-treated eyes did not develop IOP elevation with ΔIOP of 11.8 (±1.3) mm Hg 8 days later. In all tPA-treated eyes, IOP remained low until the end of the study. mRNA levels in the trabecular meshwork were decreased for plasminogen activator tissue (PLAT), increased for matrix-metalloproteinase 1 (MMP-1), and stable for plasminogen activator inhibitor 1 (PAI-1), MMP-2, MMP-9, and MMP-13 in tPA-treated eyes compared with contralateral controls. PAI-1 mRNA levels in ciliary processes also remained similar. CONCLUSIONS: Recombinant human tPA is effective in both preventing and reversing steroid-induced IOP elevation in sheep. Tissue plasminogen activator may be useful as a therapeutic agent in steroid-induced glaucoma.