SPR Study Research Articles

Exploring the binding interactions of NOP receptor with designed natural phytochemical-neuropeptide conjugates: an in silico and SPR study

The Nociceptin/orphanin FQ peptide (NOP) receptor is considered a member of the opioid receptor subfamily of G-protein coupled receptors (GPCRs) which has been shown to be present in many parts of the central nervous system (CNS). It plays biologically diverse roles in pain modulation, immune response and in neurodegenerative diseases. In this work, phytochemical conjugates of two known neuropeptides, melanocyte inhibition factor (MiF-1) and mammalian amidated neuropeptide NPFF with pain modulating ability were developed. The binding interactions of those conjugates with NOP receptor was examined as an approach to develop novel natural compounds that can modulate NOP receptor activity. The selected phytochemicals are well-known for their antioxidant abilities and are derived either from natural alkaloids (betanin), polyphenols (gallic acid and sinapic acid) or terpenes (pomolic acid). Each of the phytochemicals selected are antioxidants which may play a role in mitigating diseases. Three conjugates of betanin were designed with each peptide by conjugating each of the three carboxylic acid groups of betanin with the peptides, while all others were mono-conjugates. Our results indicated that the betanin conjugates with both peptides showed strong binding interactions while the pomolate-peptide conjugates showed moderate binding. In general, NPFF and its conjugates showed stronger binding with the receptor. Docking and molecular dynamics studies revealed that binding interactions occurred at the binding pocket encompassing the transmembrane helices TM1, TM3 and TM7 in most cases, with the ligands binding deep within the hydrophobic core. The binding interactions were further confirmed experimentally through SPR analysis, which also showed higher binding with the betanin conjugates. MMGBSA studies indicated that the binding energies of MiF-1 conjugates were higher compared to neat MiF-1. However, in the case of NPFF, while the betanin conjugates showed enhancement, in some cases the binding energies were found to be slightly reduced compared to neat NPFF. Overall our studies reveal that such natural phytochemical derivatives that can bind to the NOP receptor when conjugated to the mammalian amidated neuropeptide NPFF and the short sequence of melanocyte inhibiting factor MiF-1 may be potentially developed for further laboratory studies for potential pharmaceutical applications.

Synthesis of multivalent sialyllactose-conjugated PAMAM dendrimers: Binding to SARS-CoV-2 spike protein and influenza hemagglutinin

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) and influenza viruses have spread around the world at an unprecedented rate. Despite multiple vaccines, new variants of SARS-CoV-2 and influenza have caused a remarkable level of pathogenesis. The development of effective antiviral drugs to treat SARS-CoV-2 and influenza remains a high priority. Inhibiting viral cell surface attachment represents an early and efficient means to block virus infection. Sialyl glycoconjugates, on the surface of human cell membranes, play an important role as host cell receptors for influenza A virus and 9-O-acetyl-sialylated glycoconjugates are receptors for MERS, HKU1 and bovine coronaviruses. We designed and synthesized multivalent 6′-sialyllactose-counjugated polyamidoamine dendrimers through click chemistry at room temperature concisely. These dendrimer derivatives have good solubility and stability in aqueous solutions. SPR, a real-time analysis quantitative method for of biomolecular interactions, was used to study the binding affinities of our dendrimer derivatives by utilizing only 200 micrograms of each dendrimer. Three SARS-CoV-2 S-protein receptor binding domain (wild type and two Omicron mutants) bound to multivalent 9-O-acetyl-6′-sialyllactose-counjugated and 6′-sialyllactose-counjugated dendrimers bound to a single H3N2 influenza A virus's HA protein (A/Hong Kong/1/1968), the SPR study results suggest their potential anti-viral activities.

A small-molecule inhibitor of Keap1-Nrf2 interaction attenuates sepsis by selectively augmenting the antibacterial defence of macrophages at infection sites.

Macrophages at infection sites are considered as the promising therapeutic targets to prevent sepsis development. The Nrf2/Keap1 system acts as a critical modulator of the antibacterial activity of macrophages. Recently, Keap1-Nrf2 protein-protein interaction (PPI) inhibitors have emerged as safer and stronger Nrf2 activators; however, their therapeutic potential in sepsis remains unclear. Herein, we report a unique heptamethine dye, IR-61, as a Keap1-Nrf2 PPI inhibitor that preferentially accumulates in macrophages at infection sites. A mouse model of acute lung bacterial infection was used to investigate the biodistribution of IR-61. SPR study and CESTA were used to detect the Keap1 binding behaviour of IR-61 invitro and in cells. Established models of sepsis in mice were used to determine the therapeutic effect of IR-61. The relationship between Nrf2 levels and sepsis outcomes was preliminarily investigated using monocytes from human patients. Our data showed that IR-61 preferentially accumulated in macrophages at infection sites, enhanced bacterial clearance, and improved outcomes in mice with sepsis. Mechanistic studies indicated that IR-61 potentiated the antibacterial function of macrophages by activating Nrf2 via direct inhibition of the Keap1-Nrf2 interaction. Moreover, we observed that IR-61 enhanced the phagocytic ability of human macrophages, and the expression levels of Nrf2 in monocytes might be associated with the outcomes of sepsis patients. Our study demonstrates that the specific activation of Nrf2 in macrophages at infection sites is valuable for sepsis management. IR-61 may prove to be a Keap1-Nrf2 PPI inhibitor for the precise treatment of sepsis. This work was supported by the National Natural Science Foundation of China (Major program 82192884), the Intramural Research Project (Grants: 2018-JCJQ-ZQ-001 and 20QNPY018), and the Chongqing National Science Foundation (CSTB2022NSCQ-MSX1222).

Pixantrone confers radiosensitization in KRAS mutated cancer cells by suppression of radiation-induced prosurvival pathways

Radioresistance towards radiation therapy has generated the need for the development of radiosensitizers as a potential drug. KRAS mutation brings radioresistance in tumor cells. The present work proves sensitization of cancer cells towards radiotherapy through inhibition of KRAS activation. Acquiring a drug repurposing approach, the in-silico screening revealed that pixantrone, an antineoplastic drug, possesses a high affinity towards KRAS G12C and G12D subtypes. The SPR study suggests that maximum affinity of pixantrone was observed with KRAS G12C>WT>G12D and G12S. Pixantrone potentially inhibited the KRAS activation in stable transfectants G12C and G12D cell lines and radiosensitized distinct KRAS mutant subtype cells. The combination of pixantrone with radiation causes enhanced dsDNA breaks along with enhanced ATM expression, and increased late apoptosis. The preclinical studies on NCr-fox1nu xenograft mice showed potent inhibition of tumor progression and prolonged survival of mcie due to the radiosensitizing effect of pixantrone. Radiation-induced activation of key effector proteins of RAS downstream pathways, like MAPK and PI3K/Akt/mTOR pathways, were downregulated in tumor cells upon combination treatment. Interestingly, a robust upregulation of senescence marker p21 was observed in the tumor cells in combination treatment. These findings reveal a convergence between KRAS signaling, pixantrone treatment, and radiation conferring tumor cell death.

Natural triterpenoids from licorice potently inhibit SARS-CoV-2 infection

IntroductionThe COVID-19 global epidemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a great public health emergency. Discovering antiviral drug candidates is urgent for the prevention and treatment of COVID-19. ObjectivesThis work aims to discover natural SARS-CoV-2 inhibitors from the traditional Chinese herbal medicine licorice. MethodsWe screened 125 small molecules from Glycyrrhiza uralensis Fisch. (licorice, Gan-Cao) by virtual ligand screening targeting the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. Potential hit compounds were further evaluated by ELISA, SPR, luciferase assay, antiviral assay and pharmacokinetic study. ResultsThe triterpenoids licorice-saponin A3 (A3) and glycyrrhetinic acid (GA) could potently inhibit SARS-CoV-2 infection, with EC50 of 75 nM and 3.17 µM, respectively. Moreover, we reveal that A3 mainly targets the nsp7 protein, and GA binds to the spike protein RBD of SARS-CoV-2. ConclusionIn this work, we found GA and A3 from licorice potently inhibit SARS-CoV-2 infection by affecting entry and replication of the virus. Our findings indicate that these triterpenoids may contribute to the clinical efficacy of licorice for COVID-19 and could be promising candidates for antiviral drug development.

In-situ electrochemical SPR study of gold surface smoothing by repetitive cathodic deposition and anodic dissolution of copper in an ionic liquid

Abstract We performed in-situ analysis of the initial process of copper electrodeposition in an ionic liquid (IL), 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide (C4mimTFSA), using electrochemical surface plasmon resonance (ESPR), where the SPR resonance angle (Δθ) was recorded simultaneously with cyclic voltammograms (CVs) at the gold interface of C4mimTFSA. Δθ shifted at the potentials where faradaic current appears in the CVs, indicating that SPR probes the redox processes of copper between Cu2+, Cu+, and Cu metal. In stark contrast to the fact that the CVs are not cycle dependent, the amount of the Δθ shift due to the copper electrodeposition decreased with increasing the CV cycle. A model reflectivity analysis using the Bruggeman effective medium approximation predicted that this decrease in Δθ is due to the decrease in the roughness of the gold surface, and it was actually confirmed by ex-situ atomic force microscopy observation. Since the dissolution of gold was found to be negligible from the atomic absorption measurement of IL after the ESPR measurements, the roughness decrease of the gold surface is likely due to the surface diffusion of gold atoms promoted during copper electrodeposition and dissolution processes. It was found that ESPR can track the surface roughness change of the gold electrode in an in-situ manner in the order of A.

Toward a treatment of diabesity: In vitro and in vivo evaluation of uncharged bromophenol derivatives as a new series of PTP1B inhibitors

Protein tyrosine phosphatase 1B (PTP1B) has been considered as a validated biological target for type 2 diabetes treatment, but past endeavors to develop inhibitors of PTP1B into drugs have been unsuccessful. Two challenging aspects are selective inhibition and cell permeability. A structure-based strategy was employed to develop uncharged bromophenols as a new series of PTP1B inhibitors. The most potent compound 22 (LXQ46) inhibited PTP1B with an IC50 value of 0.190 μM, and showed remarkable selectivity over other protein tyrosine phosphatases (PTPs, 20–200 folds). In the SPR study, increasing concentrations of compound 22 led to concentration-dependent increases in binding responses, indicating that compound 22 could bind to the surface of PTP1B via noncovalent means. By treating insulin-resistant C2C12 myotubes with compound 22, enhanced insulin and leptin signaling pathways were observed. Long-term oral administration of compound 22 reduced the blood glucose level of diabetic BKS db mice. The glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) in BKS db mice showed that oral administration of compound 22 could increase insulin sensitivity. In addition, long-term oral administration of compound 22 could protect mice from obesity, which was not the result of toxicity. Our pharmacokinetics results from the rat-based assays showed that orally administered compound 22 was absorbed rapidly from the gastrointestinal tract, extensively distributed to the tissues, and rapidly eliminated from the body. All these results indicate that compound 22 could serve as a qualified agent to treat type II diabetes.

Modification of phage display technique for improved screening of high-affinity binding peptides

The phage display technique is a combinatorial technology in which random peptides are displayed on the surface of the phage; it is widely used to identify high-affinity peptides that bind to a target protein. However, this technique presents several problems due to non-specific binding of the phages and steric hindrance caused by blocking agents. To overcome these problems, we tested two modified methods and compared their screening performance with that of the conventional method. We used poly-His-tagged human epidermal growth factor receptor 2 (HER2) as a target protein and silica-coated magnetic particles (MPs) with an immobilized nickel-nitrilotriacetic acid ligand as a solid matrix. Modified method #1 (#M1) included two negative selection steps against a blocking agent (bovine serum albumin) and nude Ni-NTA MPs, after the positive selection step using immobilized HER2 on MPs in the absence of BSA. Modified method #2 (#M2) allowed the binding of phages and HER2 in solution prior to immobilizing HER2 on the MP surface. The negative selection procedure was the same between them. The binding affinity of the phages screened by #M1 and #M2 was evaluated by phage ELISA. Two phages from #M2 (#M2-4 and 5) showed the highest binding, and between them #M2-5 was selected for affinity maturation by inserting a hairpin-structured peptide between the two #M2-5 peptides. SPR study showed the HER2-binding affinity was indeed improved by ca. 2000-fold to become comparable with that of the intact antibody (trastuzumab). The modified biopanning methods combined with the dimerization maturation can be an effective way to develop antibody-mimicking peptides for affinity binding.

SPR study for analysis of a water-soluble glycopolymer interface and molecular recognition properties

A glycopolymer with different mannose incorporation ratios was synthesized via a reversible addition fragmentation chain transfer with acrylamide. The polymers were immobilized onto a gold substrate by the thiol terminate. The glycopolymer layer structures and the glycopolymer–protein interactions were analyzed using a surface plasmon resonance technique. The glycopolymers formed pancake-like structures under dry conditions and were swollen in water. The interaction between the glycopolymer and the protein was enhanced by the cluster effect of the mannose units.

Kinetics and binding geometries of the complex between β2-microglobulin and its antibody: An AFM and SPR study

β2-Microglobulin (B2M) is a human protein involved in the regulation of immune response and represents a useful biomarker for several diseases. Recently, anti-B2M monoclonal antibodies have been introduced as innovative therapeutic agents. A deeper understanding of the molecular interaction between the two partners could be of utmost relevance for both designing array-based analytical devices and improving current immunotherapies. A visualization at the nanoscale performed by Atomic Force Microscopy revealed that binding of B2M to the antibody occurred according to two preferred interaction geometries. Additionally, Atomic Force Spectroscopy and Surface Plasmon Resonance provided us with detailed information on the binding kinetics and the energy landscape of the complex, both at the single molecule level and in bulk conditions. Combination of these complementary techniques contributed to highlight subtle differences in the kinetics behaviour characterizing the complexes. Collectively, the results may deserve significant interest for designing, development and optimization of novel generations of nanobiosensor platforms.

Ursolic acid derivatives as bone anabolic agents targeted to tryptophan hydroxylase 1 (Tph-1)

Tryptophan hydroxylase 1 (Tph-1) initiates the biosynthesis of peripheral serotonin. As peripheral serotonin suppresses bone formation, inhibitor of Tph-1 provides a useful tool to discover anabolic agents for osteoporosis. In the present study, series of ursolic acid (UA) derivatives were synthesized, and their inhibitory activity on serotonin biosynthesis and cytotoxicity were evaluated. Among the derivatives, 8d with potent inhibitory activity on serotonin was applied for further research. The data revealed that 8d significantly inhibited protein and mRNA expressions of Tph-1, and an SPR study indicated that 8d directly interacted to Tph-1 with a binding affinity of KD=15.09μM. Oral administration of 8d significantly prevented bone loss via suppressing serotonin biosynthesis without estrogenic side-effects in ovariectomized (OVX) rats.

Anatomical and Functional Results of Primary Pars Plana Vitrectomy in Rhegmatogenous Retinal Detachment

It was the aim of this retrospective study to analyse the anatomical success rate and functional outcome of patients with rhegmatogenous retinal detachments treated primarily by pars plana vitrectomy (PPV). 157 of 200 eyes (79%, 89 phakic (57%), 67 pseudophakic (43%), 1 aphakic) with rhegmatogenous retinal detachment were treated by primary pars plana vitrectomy. 132 cases (84%) completed 6 months, 131 (83%) 12 months, and 108 cases (69%) 24 months of follow-up. Selection of surgical methods was guided by recommendations from the SPR study. Different from these recommendations, phakic eyes were treated by primary PPV if the chance of successful scleral buckling was estimated to be < 90%. Initial retinal attachment was achieved in all eyes. In 4 eyes peripheral tractional detachment presented during silicon removal. A second surgical intervention for the treatment of re-detachment became necessary in 8 eyes during follow-up. The rate of permanent single-intervention (except silicon removal) attachment was 92.4%. Finally the retina was completely attached in all eyes. Visual acuity improved from a preoperative level of logMAR 1.01 to 0.48 at month 6, 0.40 at month 12 and 0.33 at month 24. Mean final visual acuity at month 24 was 0.32 in phakic eyes and 0.35 in pseudophakic eye (difference not significant). Significant differences in visual acuity were found in relation to the preoperative status of the fovea. The results of this case series, together with the previous published outcome of a cohort treated in the identical study period by scleral buckling, indicate that the outcome of retinal detachment surgery in an average cohort of patients can be expected to be much better than suggested by results of the SPR study.

Cyclic RGDyk-conjugated LMWH-taurocholate derivative as a targeting angiogenesis inhibitor

LMWH-taurocholate derivative (LHT7) has been reported as a novel angiogenesis inhibitor, due to its ability to bind to several kinds of growth factors, which play critical roles in tumor angiogenesis. In this study, we have highlighted the enhanced antiangiogenic activity of LHT7, by using cyclic RGDyk (cRGD), a targeting moiety that was chemically conjugated to LHT7 via amide bond. The SPR study revealed that cRGD-LHT7 bound to αvβ3 integrin as strongly as cRGD, and it bound to VEGF as strongly as LHT7. Importantly, in vitro anti-angiogenesis studies revealed that cRGD-LHT7 had a significant inhibition effect on HUVEC tubular formation. Finally, cRGD-LHT7 showed a greater inhibitory efficiency on the tumor growth in the U87MG xenograft model than the original LHT7, which was owed to its ability to target the tumor cells. All of these findings demonstrated that cRGD-LHT7 targeted αvβ3 integrin-positive cancer cells and endothelial cells, resulting in a greater anti-angiogenesis effect on the solid tumors.

Results of Primary Buckling Procedures Indicated with Regard to Recommendations of the SPR Study in Cases with Rhegmatogenous Retinal Detachment

It was the aim of this study to analyse the functional gain and anatomical success rate in a long-term observation of patients with rhegmatogenous retinal detachments treated primarily with scleral buckling (SB) indicated on the basis of results published in the SPR study. 43 of 200 eyes (21.5 %, 41 patients) with rhegmatogenous retinal detachment were selected for scleral buckling as a primary surgical intervention. 38 patients (93 %) completed 6 months, 35 patients (85 %) 12 months and 26 patients (63 %) 24 months of follow-up. Selection of surgical methods was guided by results from the SPR study. Cases were treated by scleral buckling if the chance of primary success was estimated to be at least 90 %. Primary retinal attachment was achieved in 42 of 43 eyes (98 %). The retina in one eye without primary success was attached by pp-vitrectomy and gas endotamponade. No further redetachments occurred until month 12. Two eyes developed regional retinal traction in the periphery resulting from mild PVR (1 × after 16 months, 1 × after 35 months). Both were permanently attached after pp vitrectomy. At the end of the follow-up all eyes presented complete retinal attachment. Visual acuity improved from a preoperative level of logMAR 0.39 to 0.19 at month 6, 0.16 at month 12 and 0.11 at month 24 (p < 0.03). Cases with partial or complete foveal detachment reached between month 12 and month 24 the same level of visual acuity than those without foveal involvement (p = 0.57). The results of this case series clearly indicate that scleral buckling is still an excellent choice of the treatment for approximately one fourth of all patients with rhegmatogenous retinal detachment and may lead to very good long-term results.

Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment study (SPR study): Risk assessment of anatomical outcome. SPR study report no. 7

The 'Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment study' (SPR study) is a randomized multicentre trial comparing primary vitrectomy (PV) and scleral buckling surgery (SB) for rhegmatogenous retinal detachment (RRD). This subanalysis was conducted to identify risk factors associated with anatomical outcomes. Relating the anatomical success results at the 1-year follow-up visit to pre- and intraoperative findings using multivariate statistical methods. In the phakic subtrial, anatomical success was negatively associated with the number of breaks (p < 0.0001), break extension > 1 clock hour (p = 0.0005) and intraoperative use of cryotherapy (p = 0.0484). It was positively associated with retinal breaks with irregular edges (p = 0.0353) and subretinal fluid drainage (p = 0.0155). In the pseudophakic/aphakic subtrial, anatomical success was negatively associated with the number of retinal breaks (p = 0.0004) and previous YAG capsulotomy (p = 0.0256), and the combined effect of the surgical procedure and intraoperative use of laser (p = 0.0229). Primary anatomical success is an important result for patients undergoing RRD surgery. Our data demonstrate that the final anatomical outcome is related to a higher preoperative number of breaks and cryotherapy in phakic eyes. Additional risk factors varied between phakic and pseudophakic subgroups. Our findings may be used to facilitate the prognosis of future patients with RRD.

Prognostic factors for anatomical and functional results after retinal detachment surgery. The SPR study

AbstractPurpose In the "Scleral buckling vs. primary vitrectomy in rhegmatogenous retinal detachment study (SPR study)" two different surgical methods for the treatment of retinal detachment (RD) were compared in a randomised prospective multicentre clinical trial. This secondary analysis was conducted to investigate possible associations between pre‐ and intraoperative factors with the functional and anatomical outcomes.Methods Univariate and multivariate analysis of 48 pre‐ and intraoperative factors and their association with anatomical outcome, functional outcome and the number of secondary surgical interventions.Results In phakic patients, a significant correlation of successful outcome could be associated with number of retinal breaks, large breaks, cryotherapy, duration of symptoms, baseline visual acuity, central RD, total RD, drainage during buckling surgery and chain formation of breaks. In pseudophakic patients, factors identified were number of breaks, capsular fibrosis, Yag‐laser capsulotomy, retinal laser photocoagulation, and inferior RD.Conclusion The most important risk factor for functional and anatomical failure was a higher number of retinal breaks. Other risk factors varied between the phakic and pseudophakic patients as well as between functional and anatomical outcomes. These findings are of clinical importance for identification of patients with a higher risk for failure and for the planning of future trials on RD surgery.

Anti-proliferative effects of O-acyl-low-molecular-weight heparin derivatives on bovine pulmonary artery smooth muscle cells.

Heparin (HP) inhibits the growth of several cell types in vitro including bovine pulmonary artery (BPA) smooth muscle cells (SMCs). In initial studies we discovered that an O-hexanoylated low-molecular-weight (LMW) HP derivative having acyl groups with 6-carbon chain length was more potent inhibitor of BPA-SMCs than the starting HP. We prepared several O-acylated LMWHP derivatives having 4-, 6-, 8-, 10-, 12-, and 18- carbon acyl chain lengths to determine the optimal acyl chain length for maximum anti-proliferative properties of BPA-SMCs. The starting LMWHP was prepared from unfractionated HP by sodium periodate treatment followed by sodium borohydride reduction. The tri-n-butylammonium salt of this LMWHP was O-acylated with butanoic, hexanoic, octanoic, decanoic, dodecanoic, and stearyl anhydrides separately to give respective O-acylated LMWHP derivatives. Gradient polyacrylamide gel electrophoresis (PAGE) was used to examine the average molecular weights of those O-acylated LMWHP derivatives. NMR analysis indicated the presence of one O-acyl group per disaccharide residue. Measurement of the inhibition of BPA-SMCS as a function of O-acyl chain length shows two optima, at a carbon chain length of 6 (O-hexanoylated LMWHP) and at a carbon chain length 12-18 (O-dodecanoyl and O-stearyl LMWHPs). A solution competition SPR study was performed to test the ability of different O-acylated LMWHP derivatives to inhibit fibroblast growth factor (FGF) 1 and FGF2 binding to surface-immobilized heparin. All the LMWHP derivatives bound to FGF1 and FGF2 but each exhibited slightly different binding affinity.

Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment study (SPR Study): predictive factors for functional outcome. Study report no. 6

To identify risk factors associated with best-corrected visual acuity (BCVA) 1 year after initial surgery following primary vitrectomy (PV) and scleral buckling surgery (SB) for rhegmatogenous retinal detachment (RRD). Relating the final BCVA at the 1-year follow-up visit to pre- and intraoperative findings in the "randomized, prospective, multicenter clinical trial comparing scleral buckling versus primary vitrectomy for repair of rhegmatogenous retinal detachment" (SPR Study) using multivariate statistical methods. In the phakic subtrial, final BCVA is associated with the number of breaks (p = 0.0259), duration of symptoms (p = 0.0476), baseline BCVA (p = 0.0002), retinal detachment central to major vessels arcades (p = 0.0088), total detachment (p = 0.0027), and chain formation of breaks (p = 0.0129). In the pseudophakic/aphakic subtrial, final BCVA is related to the number of retinal breaks (p = 0.0010), secondary cataract or central capsular fibrosis (p = 0.0141), intraoperative laser photocoagulation (p = 0.0373), and inferior detachment with breaks below the 4 and 8 o'clock positions (p = 0.0173). Final BCVA is the most important outcome for patients undergoing RRD surgery. Our results demonstrate that the final BCVA is related to a higher preoperative number of breaks in both subtrials. Additional risk factors varied between phakic and pseudophakic subgroups.

How to choose the best surgical procedure?

Abstract Purpose Dealing to the localization and sealing retinal breaks, the surgical success rate for the cure of rhegmatogenous retinal detachment greatly changed with the introduction of scleral buckling (SB), intraocular gas injection, and pars plana vitrectomy (PPV). Methods In localized cases, pneumatic retinopexy and scleral buckling surgery (SB) remains the most popular surgical methods. Complicated cases with PVR grade B or C, giant tears, or macular holes are most commonly treated with primary pars plana vitrectomy. A large group of rhegmatogenous RDs with medium severity that comprise about 30% of all primary rhegmatogenous RDs in the Scleral Buckling versus Primary Vitrectomy in Rhegmatogenous Retinal Detachment recruitment study, were treated by SB and PPV. Advances in vitrectomy instrumentation and wideangle imaging systems have increased the popularity of PPV. Results The decision by the surgeon to use scleral buckling rather than PPV depends on a number of factors, including the lens status, size and location of breaks, patient compliance, and individual experience. Initial PPV may be successful for phakic patients. However, the SPR study shows a benefit of SB in phakic eyes with respect to BCVA improvement. Although no difference in BCVA was demonstrated in the pseudophakic trial, PPV was recommend for pseudophakic RD based on a better anatomical outcome. Conclusion There was a significant trend towards more frequently employing primary PPV (with or without SB) for the management of primary RRD. A significant improvement in the primary success rates for RD, were shown for all retinal surgical modalities applied for the treatment of rhegmatogenous retinal detachment.

Synthesis of Galabiose-chitosan Conjugate as Potent Inhibitor of Streptococcus suis Adhesion

The aim of this work is to construct a safe and effective drug candidate against Streptococcus suis infection. A panel of chitosan-based polymer conjugates with branched galabiose (Galalpha1-4Gal) side chains was synthesized as inhibitors of S. suis adhesion. The synthesis was achieved by using an aldehyde-functionalized galabiose derivative to graft it onto chitosan amino groups. Structural compositions of the conjugates were verified by 1H NMR spectroscopy and CHN elemental analyses. Potent inhibitory activities of the conjugates against S. suis adhesion to human erythrocytes were determined at low nanomolar concentration by HAI assay. An SPR study revealed a high affinity binding (Kd=39.6 nM) of the conjugate with BSI-B4 lectin. By using biocompatible chitosan as the scaffold for presenting S. suis -specific galabiose units, as well as the concise route tailored for the conjugate syntheses, the present study provides a practical way for explorations of new anti- S. suis therapies.