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Langmuir : the ACS Journal of Surfaces... Mar 2024Amphiphilic diblock copolymers containing a block of 2-methacryloyloxyethyl phosphorylcholine (MPC) with unique properties to prevent nonspecific protein adsorption and...
Amphiphilic diblock copolymers containing a block of 2-methacryloyloxyethyl phosphorylcholine (MPC) with unique properties to prevent nonspecific protein adsorption and enhance lubrication in aqueous media and a block of dopamine methacrylamide (DOPMA) distinguished by excellent adhesion performance were synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization for the first time. The DOPMA monomer with an acetonide-protected catechol group (acetonide-protected dopamine methacrylamide (ADOPMA)) was used, allowing the prevention of undesirable side reactions during polymerization and oxidation during storage. The adsorption behavior of the diblock copolymers with protected and unprotected catechol groups on gold surfaces was probed using attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy, surface-enhanced infrared absorption spectroscopy (SEIRAS), and reflection-absorption infrared spectroscopy (RAIRS). The copolymers pMPC--pADOPMA demonstrated physisorption with rapid adsorption and ultrasound-assisted desorption, while the copolymers pMPC--DOPMA exhibited chemical adsorption with slower dynamics but a stronger interaction with the gold surface. SEIRAS and RAIRS allowed proving the reorientation of the diblock copolymers during adsorption, demonstrating the exposure of the pMPC block toward the aqueous phase.
PubMed: 38456424
DOI: 10.1021/acs.langmuir.3c03925 -
Monitoring the Long-Term Effectiveness of Miltefosine in Indian Post-Kala-Azar Dermal Leishmaniasis.The American Journal of Tropical... Apr 2024Post-kala-azar dermal leishmaniasis (PKDL), the dermal sequel to visceral leishmaniasis (VL), is characterized by hypopigmented macules (macular) and/or papules and...
Post-kala-azar dermal leishmaniasis (PKDL), the dermal sequel to visceral leishmaniasis (VL), is characterized by hypopigmented macules (macular) and/or papules and nodules (polymorphic). Post-kala-azar dermal leishmaniasis plays a significant role in disease transmission, emphasizing the need for monitoring chemotherapeutic effectiveness. Accordingly, this study aimed to quantify the parasite burden in PKDL patients after treatment with miltefosine by a quantitative polymerase chain reaction (qPCR). A Leishmania kinetoplastid gene-targeted qPCR was undertaken using DNA from skin biopsy specimens of patients with PKDL at three time points, i.e., at disease presentation (week 0, n = 157, group 1), upon completion of treatment (week 12, n = 39, group 2), and at any time point 6 months after completion of treatment (week ≥36, n = 54, group 3). A cycle threshold (Ct) <30 was considered the cutoff for positivity, and load was quantified as the number of parasites/µg genomic DNA (gDNA); cure was considered when samples had a Ct >30. The parasite load at disease presentation (group 1) was 10,769 (1,339-80,441)/µg gDNA (median [interquartile range]). In groups 2 and 3, qPCR results were negative in 35/39 cases (89.7%) and 48/54 cases (88.8%), respectively. In the 10/93 (10.8%) qPCR-positive cases, the parasite burdens in groups 2 and 3 were 2,420 (1,205-5,661)/µg gDNA and 22,195 (5,524-100,106)/µg gDNA, respectively. Serial monitoring was undertaken in 45 randomly selected cases that had completed treatment; all cases in groups 2 or 3 had a Ct >30, indicating cure. Overall, qPCR confirmed an 89.2% cure (as 83/93 cases showed parasite clearance), and the persistent qPCR positivity was attributed to nonadherence to treatment or unresponsiveness to miltefosine and remains to be investigated.
Topics: Humans; Leishmaniasis, Visceral; Leishmaniasis, Cutaneous; Leishmania; DNA; Leishmania donovani; Phosphorylcholine
PubMed: 38442428
DOI: 10.4269/ajtmh.23-0197 -
ACS Omega Feb 2024Graphene nanosheets are highly valued in the biomedical field due to their potential applications in drug delivery, biological imaging, and biosensors. Their biological...
Graphene nanosheets are highly valued in the biomedical field due to their potential applications in drug delivery, biological imaging, and biosensors. Their biological effects on mammalian cells may be influenced by cholesterols, which are crucial components in cell membranes that take part in many vital processes. Therefore, it is particularly important to investigate the effect of cholesterols on the transport mechanism of graphene nanosheets in the cell membrane as well as the final stable configuration of graphene, which may have an impact on cytotoxicity. In this paper, the molecular details of a graphene nanosheet interacting with a 1,2-dipalmitoyl--glycero-3-phosphorylcholine (DPPC) membrane with cholesterols were studied using molecular dynamics simulations. Results showed that the structure of the graphene nanosheet transits from the cut-in state in a pure DPPC membrane to being sandwiched between two DPPC leaflets when cholesterols reach a certain concentration. The underlying mechanism showed that cholesterols are preferentially adsorbed on the graphene nanosheet, which causes a larger disturbance to the nearby DPPC tails and thus guides the graphene nanosheet into the core of lipid bilayers to form a sandwiched structure. Our results are helpful for understanding the fundamental interaction mechanism between the graphene nanosheet and cell membrane and to explore the potential applications of the graphene nanosheet in biomedical sciences.
PubMed: 38434853
DOI: 10.1021/acsomega.3c08236 -
NPJ Regenerative Medicine Mar 2024Pathophysiologic inflammation, e.g., from HSV-1 viral infection, can cause tissue destruction resulting in ulceration, perforation, and ultimately blindness. We...
Pathophysiologic inflammation, e.g., from HSV-1 viral infection, can cause tissue destruction resulting in ulceration, perforation, and ultimately blindness. We developed an injectable Cornea-in-a-Syringe (CIS) sealant-filler to treat damaged corneas. CIS comprises linear carboxylated polymers of inflammation-suppressing 2-methacryloyloxyethyl phosphorylcholine, regeneration-promoting collagen-like peptide, and adhesive collagen-citrate glue. We also incorporated GF19, a modified anti-viral host defense peptide that blocked HSV-1 activity in vitro when released from silica nanoparticles (SiNP-GF19). CIS alone suppressed inflammation when tested in a surgically perforated and HSV-1-infected rabbit corneal model, allowing tissue and nerve regeneration. However, at six months post-operation, only regenerated neocorneas previously treated with CIS with SiNP-GF19 had structural and functional features approaching those of normal healthy corneas and were HSV-1 virus-free. We showed that composite injectable biomaterials can be designed to allow regeneration by modulating inflammation and blocking viral activity in an infected tissue. Future iterations could be optimized for clinical application.
PubMed: 38429307
DOI: 10.1038/s41536-024-00355-1 -
Emerging Infectious Diseases Mar 2024Disseminated leishmaniasis (DL) is an emergent severe disease manifesting with multiple lesions. To determine the relationship between immune response and clinical and...
Disseminated leishmaniasis (DL) is an emergent severe disease manifesting with multiple lesions. To determine the relationship between immune response and clinical and therapeutic outcomes, we studied 101 DL and 101 cutaneous leishmaniasis (CL) cases and determined cytokines and chemokines in supernatants of mononuclear cells stimulated with leishmania antigen. Patients were treated with meglumine antimoniate (20 mg/kg) for 20 days (CL) or 30 days (DL); 19 DL patients were instead treated with amphotericin B, miltefosine, or miltefosine and meglumine antimoniate. High levels of chemokine ligand 9 were associated with more severe DL. The cure rate for meglumine antimoniate was low for both DL (44%) and CL (60%), but healing time was longer in DL (p = 0.003). The lowest cure rate (22%) was found in DL patients with >100 lesions. However, meglumine antimoniate/miltefosine treatment cured all DL patients who received it; therefore, that combination should be considered as first choice therapy.
Topics: Humans; Leishmania braziliensis; Meglumine Antimoniate; Leishmaniasis, Cutaneous; Leishmania; Phosphorylcholine
PubMed: 38407142
DOI: 10.3201/eid3003.230786 -
Heliyon Feb 2024Surface modification of electrically neutral hydrophilic polymers is one of the most promising methods for preventing biofouling and biological contamination by proteins...
Surface modification of electrically neutral hydrophilic polymers is one of the most promising methods for preventing biofouling and biological contamination by proteins and bacteria. Surface modification of inorganic materials such as silica-based glass can render them more durable and thus help in achieving the sustainable development goals. This study reports a novel method for the simple and effective surface modification of glass surfaces with amphiphilic block copolymers possessing the silane coupling segment composed of 3-(methacryloyloxy)propyltris (trimethylsilyloxy) silane and 3-methacryloxypropyltrimethoxysilane. The ability of hydrophilic segments composed of either 2-methacryloyloxyethyl phosphorylcholine (MPC) or poly(ethylene glycol) methyl ether methacrylate (mOEGMA) to prevent bacterial adhesion was investigated. The target block copolymers were prepared by reversible addition-fragmentation chain transfer polymerization and the monomer units of the hydrophilic segments were controlled to be either 120 or 160. The polymers were modified on the substrate by dip-coating. Contact angle measurements indicated that the block copolymer with the PMPC hydrophilic segment formed a hydrophilic surface without pre-hydration, while those with the PmOEGMA hydrophilic segment-coated surface became hydrophilic upon immersion in water. The block copolymer-coated surfaces decreased adhesion, and a significant reduction was observed with the MPC-type block copolymer. The following surface design guidelines were thus concluded: (1) the block copolymer is superior to the random copolymer and (2) increasing the hydrophilic segment length further decreases bacterial adhesion.
PubMed: 38404882
DOI: 10.1016/j.heliyon.2024.e26347 -
Medicina (Kaunas, Lithuania) Feb 2024: Dry eye disease (DED) affects 5-50% of the global population and deeply influences everyday life activities. This study compared the efficacy, tolerability, and safety... (Randomized Controlled Trial)
Randomized Controlled Trial
: Dry eye disease (DED) affects 5-50% of the global population and deeply influences everyday life activities. This study compared the efficacy, tolerability, and safety of novel Respilac artificial tears containing lipidure and hypromellose (HPMC) with the widely used Nextal artificial tears, which are also HPMC-based, for the treatment of moderate DED in contact lenses (CL) wearers. : In a prospective, single-center, randomized investigation, 30 patients aged ≥18 years, diagnosed with moderate DED, and wearing CL were randomly assigned to the Respilac ( = 15) or Nextal group ( = 15). Patients self-administrated one drop of Respilac or Nextal in both eyes three times daily for 21 days. Changes in the endpoint (visual analogue scale (VAS) score for ocular tolerability, symptom assessment in dry eye (SANDE) score, non-invasive first break-up time (NIF-BUT) results, tear analysis value, meibography results, and CL tolerability results were assessed, comparing treatment groups and time-point evaluations. Adverse events (AEs) were also recorded and evaluated. : VAS scores decreased with time < 0.001) in both groups, showing no statistically significant difference among them ( = 0.13). Improvements were also detected from screening to end-of-treatment, which were indicated by the SANDE scores for severity and frequency ( < 0.001) and by tear analysis results ( < 0.001) with no observed difference between the Nextal and Respilac arms. NIF-BUT, meibography, and CL tolerability values were shown to be non-significantly affected by treatment and time. There were no AEs detected in this study cohort. : Respilac was confirmed to be effective, safe, and well-tolerated. Lipidure-based ophthalmic solution was shown not to be inferior to the currently used Nextal, however, showing improvements in DED symptoms. Within the existing literature, our study is one of the first to report that MPC plus HPMC-containing eye drops are an effective option for the treatment of moderate dry eye disease and desiccation damage prevention in contact lens wearers.
Topics: Humans; Adolescent; Adult; Lubricant Eye Drops; Hypromellose Derivatives; Prospective Studies; Dry Eye Syndromes; Contact Lenses; Tears
PubMed: 38399574
DOI: 10.3390/medicina60020287 -
Neurosurgery Feb 2024The pipeline embolization device (PED) Flex with Shield technology is a third-generation flow diverter used for intracranial aneurysm treatment designed to decrease...
BACKGROUND AND OBJECTIVES
The pipeline embolization device (PED) Flex with Shield technology is a third-generation flow diverter used for intracranial aneurysm treatment designed to decrease thrombogenicity through a phosphorylcholine coating. Herein, we aim to compare the rate of thromboembolic events in PED with Shield technology and PED without it through propensity score matching.
METHODS
We conducted a retrospective analysis of aneurysms treated with PED first-generation/PED Flex and PED with Shield between 2013 and 2023 at a single academic institution. Patients were matched through propensity score by controlling for confounding factors including age, smoking history, diabetes, previous subarachnoid hemorrhage, modified Rankin Scale pretreatment, location, aneurysm size, previous treatment, and clopidogrel or aspirin resistance. After matching, we evaluated for periprocedural and postoperative thromboembolic events. Data analysis was performed using Stata 14.
RESULTS
A total of 543 patients with 707 aneurysms treated in 605 procedures were included in the analysis. From these, 156 aneurysms were treated with PED with Shield (22.07%) and 551 (77.93%) without Shield technology. Propensity score matching resulted in 84 matched pairs. The rate of thromboembolic events was 3.57% for PED Shield and 10.71% for PED first-generation/PED Flex (P = .07), while retreatment rates were 2.38% for PED Shield and 8.32% for PED Flex (P = .09). Complete occlusion at first (P = .41) and last imaging follow-up (P = .71), in-stent stenosis (P = .95), hemorrhagic complications (P = .31), and functional outcomes (P = .66) were comparable for both groups.
CONCLUSION
This is the first study in the literature performing a propensity scored-matched analysis comparing PED with PED with Shield technology. Our study suggests a trend toward lower thromboembolic events for PED Shield, even after controlling for aspirin and clopidogrel resistance, and a trend toward lower aneurysm retreatment rates with PED Shield, without reaching statistical significance.
PubMed: 38391195
DOI: 10.1227/neu.0000000000002883 -
Pharmaceutical Research Mar 2024Panax notoginseng saponins (PNS) are commonly used first-line drugs for treating cerebral thrombosis and stroke in China. However, the synchronized and targeted delivery...
BACKGROUND
Panax notoginseng saponins (PNS) are commonly used first-line drugs for treating cerebral thrombosis and stroke in China. However, the synchronized and targeted delivery of active ingredients in traditional Chinese medicine (TCM) poses a significant challenge for modern TCM formulations.
METHODS
Bovine serum albumin (BSA) was modified using 2-methacryloyloxyethyl phosphorylcholine (MPC), an analog of acetylcholine, and subsequently adsorbed the major PNS onto the modified albumin to produce MPC-BSA@PNS nanoparticles (NPs). This novel delivery system facilitated efficient and synchronized transport of PNS across the blood-brain barrier (BBB) through active transport mediated by nicotinic acetylcholine receptors.
RESULTS
In vitro experiments demonstrated that the transport rates of R, R, R, and R across the BBB were relatively synchronous in MPC-BSA@PNS NPs compared to those in the PNS solution. Additionally, animal experiments revealed that the brain-targeting efficiencies of R + R + R in MPC-BSA@PNS NPs were 2.02 and 7.73 times higher than those in BSA@PNS NPs and the free PNS group, respectively.
CONCLUSIONS
This study presents a simple and feasible approach for achieving the targeted delivery of complex active ingredient clusters in TCM.
Topics: Animals; Saponins; Panax notoginseng; Acetylcholine; Brain; Albumins
PubMed: 38383935
DOI: 10.1007/s11095-024-03670-w -
Cardiovascular Research Mar 2024The adaptive immune response plays an important role in atherosclerosis. In response to a high-fat/high-cholesterol (HF/HC) diet, marginal zone B (MZB) cells activate an...
AIMS
The adaptive immune response plays an important role in atherosclerosis. In response to a high-fat/high-cholesterol (HF/HC) diet, marginal zone B (MZB) cells activate an atheroprotective programme by regulating the differentiation and accumulation of 'poorly differentiated' T follicular helper (Tfh) cells. On the other hand, Tfh cells activate the germinal centre response, which promotes atherosclerosis through the production of class-switched high-affinity antibodies. We therefore investigated the direct role of Tfh cells and the role of IL18 in Tfh differentiation in atherosclerosis.
METHODS AND RESULTS
We generated atherosclerotic mouse models with selective genetic deletion of Tfh cells, MZB cells, or IL18 signalling in Tfh cells. Surprisingly, mice lacking Tfh cells had increased atherosclerosis. Lack of Tfh not only reduced class-switched IgG antibodies against oxidation-specific epitopes (OSEs) but also reduced atheroprotective natural IgM-type anti-phosphorylcholine (PC) antibodies, despite no alteration of natural B1 cells. Moreover, the absence of Tfh cells was associated with an accumulation of MZB cells with substantially reduced ability to secrete antibodies. In the same manner, MZB cell deficiency in Ldlr-/- mice was associated with a significant decrease in atheroprotective IgM antibodies, including natural anti-PC IgM antibodies. In humans, we found a positive correlation between circulating MZB-like cells and anti-OSE IgM antibodies. Finally, we identified an important role for IL18 signalling in HF/HC diet-induced Tfh.
CONCLUSION
Our findings reveal a previously unsuspected role of MZB cells in regulating atheroprotective 'natural' IgM antibody production in a Tfh-dependent manner, which could have important pathophysiological and therapeutic implications.
Topics: Humans; Mice; Animals; Immunoglobulin M; Interleukin-18; B-Lymphocytes; Atherosclerosis; Cholesterol; T-Lymphocytes, Helper-Inducer
PubMed: 38381113
DOI: 10.1093/cvr/cvae027