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Keywords = Carriere Distalizer

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15 pages, 1269 KB  
Article
Linear DNA–Chitosan Nanoparticles: Formulation Challenges and Transfection Efficiency in Lung Cell Line
by Chiara Migone, Angela Fabiano, Ylenia Zambito, Rebecca Piccarducci, Laura Marchetti, Chiara Giacomelli, Claudia Martini and Anna Maria Piras
Appl. Biosci. 2025, 4(2), 29; https://doi.org/10.3390/applbiosci4020029 - 6 Jun 2025
Viewed by 942
Abstract
Linear DNA constructs are used in gene delivery and therapy application due to their capacity of integration into the mammalian genome, offering stable transgene expression. Compared to circular plasmids, linear DNA also has the advantage that its dimension and steric hindrance are directly [...] Read more.
Linear DNA constructs are used in gene delivery and therapy application due to their capacity of integration into the mammalian genome, offering stable transgene expression. Compared to circular plasmids, linear DNA also has the advantage that its dimension and steric hindrance are directly correlated to the length of the nucleotide chain. These considerations make linear DNA an effective choice for gene delivery pilot studies, where formulations and transfection efficiency calculations are studied considering the nucleic acid dimensions. Meanwhile, the development of DNA–chitosan nanoparticles (NPs) has gained significant interest for their potential in nucleic acid delivery, especially as non-viral gene delivery systems and for embedding linear DNA fragments, as well as gene delivery to the lung. This study explored an easy polyelectrolyte complexing preparation of linear DNA-loaded chitosan nanoparticles. Among the different formulations of nanoparticles prepared, the optimal one exhibited a size of approximately 290 nm, an encapsulation efficiency of 86% and a zeta potential of 25 mV. Additionally, this study examined how the concentration of DNA in solution influenced nanoparticle formation, encapsulation efficiency and particle size. In particular, transient transfection of the chitosan–linear DNA fragment complex, encoding for green fluorescent protein (GFP), was conducted in human pulmonary distal lung cells (NCI-H441 cells), demonstrating successful cellular internalization and protein expression. These studies highlight the potential of DNA–chitosan NPs in nucleic acid delivery, particularly for pulmonary applications. Future works will focus on formulating the achieved carrier into an inhalable dosage form to improve its translational application. Full article
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12 pages, 290 KB  
Article
GAS5 rs145204276 Ins/Del Polymorphism Is Associated with CRC Susceptibility in a Romanian Population
by Cecil Sorin Mirea, Michael Schenker, Bianca Petre-Mandache, Mihai-Gabriel Cucu, Georgiana-Cristiana Camen, Ionică Daniel Vîlcea, Bogdan Cristian Albu, Cosmin Vasile Obleagă, Mihai Călin Ciorbagiu, Ioana Streață, Răzvan Mihail Pleșea, Anca-Lelia Riza and Florin Burada
Int. J. Mol. Sci. 2025, 26(7), 3078; https://doi.org/10.3390/ijms26073078 - 27 Mar 2025
Viewed by 642
Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality, influenced by both genetic and epigenetic factors. Long non-coding RNAs (lncRNAs) such as GAS5 and CASC8 have been implicated in cancer susceptibility. This study aimed to assess the association of GAS5 [...] Read more.
Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality, influenced by both genetic and epigenetic factors. Long non-coding RNAs (lncRNAs) such as GAS5 and CASC8 have been implicated in cancer susceptibility. This study aimed to assess the association of GAS5 rs145204276 ins/del and CASC8 rs10505477 A>G polymorphisms with CRC risk in a Romanian population. A case-control study was conducted, including 156 CRC patients and 195 healthy controls. Genotyping for GAS5 and CASC8 polymorphisms was performed using real-time PCR, and the association with CRC risk was evaluated using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). The carriers of GAS5 rs145204276 del allele was significantly associated with increased CRC risk (OR: 2.13, 95% CI: 1.24–3.63, p = 0.005) in a dominant model. In the subgroup analysis, the association of GAS5 rs145204276 ins/del polymorphism was restricted to distal colon cancer cases (OR: 2.98, 95% CI: 1.57–5.66, p = 0.001), advanced tumor stages (III + IV) (OR: 2.54, 95% CI: 1.31–4.91, p = 0.007), and poorly differentiated tumors (G3) (OR: 3.98, 95% CI: 1.49–10.59, p = 0.009). No significant correlation was found for the CASC8 rs10505477 A>G polymorphism. GAS5 rs145204276 polymorphism may influence CRC susceptibility, particularly in distal tumors and advanced stages. However, CASC8 rs10505477 polymorphism showed no association with CRC risk in this Romanian cohort. Full article
11 pages, 1261 KB  
Article
Nephrogenic Diabetes Insipidus Affecting Three Males in Two Generations—Case Report and Review of the Literature
by Ramona Stroescu, Adela Chiriţă-Emandi, Maria Puiu, Flavia Chisavu, Ruxandra Steflea, Gabriela Doroş and Mihai Gafencu
Children 2025, 12(2), 195; https://doi.org/10.3390/children12020195 - 6 Feb 2025
Cited by 1 | Viewed by 1240
Abstract
Background: Nephrogenic diabetes insipidus (NDI) is defined as the inability of the kidney to concentrate urine owing to the insensitivity of the distal nephron to the antidiuretic hormone, arginine vasopressin. NDI is a heterogeneous rare autosomal dominant or X-linked disease. Objective: We present [...] Read more.
Background: Nephrogenic diabetes insipidus (NDI) is defined as the inability of the kidney to concentrate urine owing to the insensitivity of the distal nephron to the antidiuretic hormone, arginine vasopressin. NDI is a heterogeneous rare autosomal dominant or X-linked disease. Objective: We present a family with nephrogenic diabetes affecting three males in two generations. Methods: We report two boys with NDI: a 4-month-old infant who was treated for fever, vomiting, and failure to thrive, and his 10-year-old uncle (the mother’s brother), who was admitted concurrently for consuming 11 L of fluid per day. According to family history, the mother’s sibling passed away at the age of two from severe hypernatremic dehydration. Results: The infant’s clinical and laboratory evaluation revealed a 7.8 mL/kg/h urine output, hypernatremic hyperchloremic alkalosis, extremely low urine density (1002), and elevated copeptin level. In contrast, the uncle’s clinical and laboratory evaluation revealed marked polyuria, low urine density, and elevated copeptin, all of which were suggestive of diabetes insipidus. After starting hydrochlorothiazide treatment (2 mg/kg/body), the infant’s urine production reduced (2.85 mL/kg/h); however, severe hypokalemia and alkalosis followed. Spironolactone, an aldosterone antagonist, were added, with good therapeutic response. Hydrochlorothiazide was administered to the uncle, and his daily fluid intake decreased to 3–4 L. Given the family history, Sanger sequencing for the AVPR2 variant was performed on the boys and the infant’s mother. Analysis showed hemizygous likely pathogenic variant c.335G>A p. (Cys112Tyr) in the 2 boys and heterozygous (carrier) status of the mother. Within the same family, we observed phenotypic heterogeneity: one child died at the age of two, another lived well into ten years without therapy, and a four month-old baby could have had a poor outcome without specific treatment. Conclusions: NDI is a rare and possibly fatal genetic disorder with heterogeneous manifestations. In families with a history of NDI, molecular genetic testing is crucial for family planning. Full article
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23 pages, 6957 KB  
Article
Exploring Thinopyrum spp. Group 7 Chromosome Introgressions to Improve Durum Wheat Performance under Intense Daytime and Night-Time Heat Stress at Anthesis
by Gloria Giovenali, Maria Lia Di Romana, Alessandra Capoccioni, Vinicio Riccardi, Ljiljana Kuzmanović and Carla Ceoloni
Plants 2024, 13(18), 2605; https://doi.org/10.3390/plants13182605 - 18 Sep 2024
Viewed by 1535
Abstract
Durum wheat (DW) is one of the major crops grown in the Mediterranean area, a climate-vulnerable region where the increase in day/night (d/n) temperature is severely threatening DW yield stability. In order to improve DW heat tolerance, the introgression of chromosomal segments derived [...] Read more.
Durum wheat (DW) is one of the major crops grown in the Mediterranean area, a climate-vulnerable region where the increase in day/night (d/n) temperature is severely threatening DW yield stability. In order to improve DW heat tolerance, the introgression of chromosomal segments derived from the wild gene pool is a promising strategy. Here, four DW-Thinopyrum spp. near-isogenic recombinant lines (NIRLs) were assessed for their physiological response and productive performance after intense heat stress (IH, 37/27 °C d/n) had been applied for 3 days at anthesis. The NIRLs included two primary types (R5, R112), carriers (+) of a differently sized Th. ponticum 7el1L segment on the DW 7AL arm, and two corresponding secondary types (R69-9/R5, R69-9/R112), possessing a Th. elongatum 7EL segment distally inserted into the 7el1L ones. Their response to the IH stress was compared to that of corresponding non-carrier sib lines (−) and the heat-tolerant cv. Margherita. Overall, the R112+, R69-9/R5+ and R69-9/R112+ NIRLs exhibited a tolerant behaviour towards the applied stress, standing out for the maintenance of leaf relative water content but also for the accumulation of proline and soluble sugars in the flag leaf and the preservation of photosynthetic efficiency. As a result, all the above three NIRLs (R112+ > R69-9/R5+ > R69-9/R112+) displayed good yield stability under the IH, also in comparison with cv. Margherita. R112+ particularly relied on the strength of spike fertility/grain number traits, while R69-9/R5+ benefited from efficient compensation by the grain weight increase. This work largely confirmed and further substantiated the value of exploiting the wild germplasm of Thinopyrum species as a useful source for the improvement of DW tolerance to even extreme abiotic stress conditions, such as the severe heat treatment throughout day- and night-time applied here. Full article
(This article belongs to the Special Issue Abiotic Stress Responses in Plants)
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12 pages, 1341 KB  
Article
Association of OPRD1 Gene Variants with Changes in Body Weight and Psychometric Indicators in Patients with Eating Disorders
by Laura González-Rodríguez, Luz María González, Angustias García-Herráiz, Sonia Mota-Zamorano, Isalud Flores and Guillermo Gervasini
J. Clin. Med. 2024, 13(17), 5189; https://doi.org/10.3390/jcm13175189 - 1 Sep 2024
Viewed by 1183
Abstract
Objectives: This study aimed to investigate whether genetic variations in the OPRD1 gene affect psychopathological symptoms and personality dimensions in eating disorders (ED) patients and/or contribute to ED risk. Methods: The study involved 221 female patients with anorexia nervosa (AN), 88 [...] Read more.
Objectives: This study aimed to investigate whether genetic variations in the OPRD1 gene affect psychopathological symptoms and personality dimensions in eating disorders (ED) patients and/or contribute to ED risk. Methods: The study involved 221 female patients with anorexia nervosa (AN), 88 with bulimia nervosa (BN), and 396 controls. Sixteen tag-single nucleotide polymorphisms (SNPs) in OPRD1 were identified. Psychometric evaluations were conducted using the Symptom Checklist 90 Revised (SCL-90R) and the Eating Disorders Inventory Test-2 (EDI-2). p-values obtained by regression models were corrected for multiple testing by the False Discovery Rate (FDR) method. Results: In AN patients, genotypes rs204077TT and rs169450TT were linked to lower body-mass index (BMI) values (FDR-q = 0.035 and 0.017, respectively), as was rs2234918 in a log-additive model (BMI: 18.0 ± 0.28, 17.22 ± 0.18 and 16.59 ± 0.39 for TT, TC and CC carriers, FDR-q = 0.012). Additionally, AN patients carrying the rs72665504AA genotype had higher scores in interpersonal distrust (FDR-q = 0.030), whilst BN carriers of rs513269TT and rs2873795TT showed lower scores in ineffectiveness (FDR-q = 0.041 and FDR-q = 0.021). In the AN group, BMI correlated with variability in a distal haplotype (rs508448/rs204077/rs223491, FDR-q = 0.028), which was also associated with the global positive symptom total (PST) index of SCL-90R (FDR-q = 0.048). Associations were more noticeable in BN patients; again, the distal region of the gene was linked to EDI-2 total scores (FDR-q = 0.004–0.048 for the four last haplotypes) and two global SCL-90R indices (GSI: FDR-q = 0.011 and positive symptom distress index (PSDI): FDR-q = 0.003 for the last s204077/rs2234918/rs169450 combination). No associations with ED risk were observed. Conclusions: Genetic variation in the OPRD1 gene, particularly in its distal region, is associated with BMI and psychopathological comorbidities in ED patients. Full article
(This article belongs to the Special Issue Diagnosis, Treatment, and Prognosis of Neuropsychiatric Disorders)
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12 pages, 919 KB  
Article
Evaluating the Effects of Carriere Motion Appliance and Twin Block Appliances in Class II Correction—A Retrospective Study
by Gilad Har Zion, Eyal Katzhendler, Amal Bader Farraj, Miryam Rabin and Shmuel Einy
Dent. J. 2024, 12(5), 119; https://doi.org/10.3390/dj12050119 - 23 Apr 2024
Cited by 2 | Viewed by 3057
Abstract
This retrospective study compared Class II orthodontic non-extraction treatment using Carriere Motion Appliance (CMA) and Twin Block (TB) appliances. Methods: The treatment of 38 patients was assessed. Pre- and post-treatment cephalometric radiographs were analyzed to evaluate skeletal, dental, and soft tissue treatment outcomes [...] Read more.
This retrospective study compared Class II orthodontic non-extraction treatment using Carriere Motion Appliance (CMA) and Twin Block (TB) appliances. Methods: The treatment of 38 patients was assessed. Pre- and post-treatment cephalometric radiographs were analyzed to evaluate skeletal, dental, and soft tissue treatment outcomes and efficacy. Results: Both appliances effectively corrected the Class II molar relationship. When measured at the distal aspect of the first molar, TB achieved 4.22 mm, while CMA had a 2.55 mm correction. When measured in the mesial aspect, the CMA achieved a 3.9 mm correction. The changes in SNB and ANB were statistically significant only in the TB group. The CMA appliance demonstrated statistically significantly less protrusion of the mandibular incisors and less upper incisor retrusion without vertical changes compared to the TB appliance. The TB demonstrated statistically significant lower lip protrusion compared to the CMA. Conclusion: The CMA corrects Class II malocclusions only by exerting a dentoalveolar influence and does not demonstrate the added effects associated with TB, such as elongation of lower facial height (LFH) and less loss of lower anchorage. Nonetheless, the correction in the TB group comprised both dentoalveolar and skeletal components. The CMA promotes a multidirectional upper and lower molar movement, and despite our 2D cephalometric analysis, we were able to estimate the extent of upper molar derotation. Full article
(This article belongs to the Special Issue Current Research Topics in Orthodontics)
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13 pages, 2437 KB  
Article
Natural Killer Cell Dysfunction in Premenopausal BRCA1 Mutation Carriers: A Potential Mechanism for Ovarian Carcinogenesis
by Shaun Haran, Kantaraja Chindera, May Sabry, Nafisa Wilkinson, Rupali Arora, Agnieszka Zubiak, Thomas E. Bartlett, Iona Evans, Allison Jones, Daniel Reisel, Chiara Herzog, Twana Alkasalias, Mark Newman, Jaeyeon Kim, Angelique Flöter Rådestad, Kristina Gemzell-Danielsson, Adam N. Rosenthal, Louis Dubeau, Mark W. Lowdell and Martin Widschwendter
Cancers 2024, 16(6), 1186; https://doi.org/10.3390/cancers16061186 - 18 Mar 2024
Cited by 1 | Viewed by 3380
Abstract
Background: Tissue-specificity for fimbrial fallopian tube ovarian carcinogenesis remains largely unknown in BRCA1 mutation carriers. We aimed to assess the cell autonomous and cell-nonautonomous implications of a germline BRCA1 mutation in the context of cancer immunosurveillance of CD3 CD56+ natural killer [...] Read more.
Background: Tissue-specificity for fimbrial fallopian tube ovarian carcinogenesis remains largely unknown in BRCA1 mutation carriers. We aimed to assess the cell autonomous and cell-nonautonomous implications of a germline BRCA1 mutation in the context of cancer immunosurveillance of CD3 CD56+ natural killer (NK) cells. Methods: Premenopausal BRCA1 mutation carriers versus age-matched non-carriers were compared. Daily urinary 5β-pregnanediol levels were used to determine progesterone metabolomics across an ovarian cycle. Using peripherally acquired NK cells the cell-mediated cytotoxicity of tumor targets (OVCAR-3, K-562) was determined using live cellular impedance (xCELLigence®) and multicolor flow cytometry. Hypoxia-inducible factor 1-alpha (HIF-1α) immunohistochemistry of cancer-free fallopian tube specimens allowed a comparison of proximal versus distal portions. Utilizing these findings the role of environmental factors relevant to the fimbrial fallopian tube (progesterone, hypoxia) on NK cell functional activity were studied in an ovarian phase-specific manner. Results: BRCA1 mutation carriers demonstrate a differential progesterone metabolome with a phase-specific reduction of peripheral NK cell functional activity. Progesterone exposure further impairs NK cell-mediated cytotoxicity in a dose-dependent manner, which is reversed with the addition of mifepristone (1.25 µM). The fimbrial fallopian tube demonstrated significantly higher HIF-1α staining, particularly in BRCA1 mutation carriers, reflecting a site-specific ‘hypoxic niche’. Exposure to hypoxic conditions (1% O2) can further impair tumor cytotoxicity in high-risk carriers. Conclusions: Phase-specific differential NK cell activity in BRCA1 mutation carriers, either systemically or locally, may favor site-specific pre-invasive carcinogenesis. These cumulative effects across a reproductive lifecycle in high-risk carriers can have a detrimental effect further supporting epidemiological evidence for ovulation inhibition. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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6 pages, 867 KB  
Communication
The Mechanics of Maxillary Molar Distal Movement Using Class II Carriere Motion Appliance: A Finite Element Study
by Yukiko Yokoi, John K. Kaku, Tatsuo Takaya and Norimasa Okafuji
Appl. Sci. 2024, 14(4), 1514; https://doi.org/10.3390/app14041514 - 13 Feb 2024
Cited by 1 | Viewed by 2366
Abstract
To clarify the mechanics of tooth movement produced by a unique distalizer, Class II Carriere Motion appliance (CMA), in which the maxillary canine is connected to the maxillary first molar with a stiff bar, long-term tooth movement was simulated by the finite element [...] Read more.
To clarify the mechanics of tooth movement produced by a unique distalizer, Class II Carriere Motion appliance (CMA), in which the maxillary canine is connected to the maxillary first molar with a stiff bar, long-term tooth movement was simulated by the finite element method (FEM). The FEM models of the maxillary canine, premolars, and first molar were made based on a dental study model. The periodontal ligament (PDL) was constructed on the root and assumed to be a nonlinear elastic material. The teeth and the alveolar bone were assumed to be rigid bodies. The tooth moved by accumulating the initial movement produced by the elastic deformation of the PDL. When retraction force was applied to the canine from the mandibular dentition, the canine tipped or rotated clockwise and extruded due to the vertical component of the retraction force. The molar and premolars also tipped and moved distally, but hardly extruded because the vertical force did not act on them. As a result of these tooth movements, the canine protruded from the dentition. An interproximal space was created between the canine and the lateral incisor. These movement patterns were similar to those in other clinical studies using the CMA. Full article
(This article belongs to the Special Issue Advances in Orthodontic Treatment)
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11 pages, 1849 KB  
Article
Three-Dimensional Force Characterizations in Maxillary Molar Distalization: A Finite Element Study
by Jianing Wang, Anastasia Tsolaki, John C. Voudouris, Thyagaseely Sheela Premaraj, Sundaralingam Premaraj, Linxia Gu and Pengfei Dong
Appl. Sci. 2023, 13(12), 7195; https://doi.org/10.3390/app13127195 - 16 Jun 2023
Cited by 2 | Viewed by 2471
Abstract
Class II malocclusion is a very common condition in orthodontic patients. The reaction force and moment on the teeth induced by a maxillary segmental distalizer (MSD) are essential for understanding tooth movement, tipping, and rotation. This work quantified the three-dimensional (3D) reaction force [...] Read more.
Class II malocclusion is a very common condition in orthodontic patients. The reaction force and moment on the teeth induced by a maxillary segmental distalizer (MSD) are essential for understanding tooth movement, tipping, and rotation. This work quantified the three-dimensional (3D) reaction force and moment on canine and molar teeth induced by three different MSDs: the JVBarre (JVB), Carriere Motion 3D (CM3D), and CM3D Clear. A patient-specific mandibular model was reconstructed based on cone-beam computed tomography (CBCT) images. Each of the three MSDs was implanted using finite element analysis (FEA). The reaction force and moment were obtained. The results show that the JVB induced less extrusion force (15% less), tipping (90% less), and rotational moment (70% less) on the canine, compared with the other two CM3Ds. However, the JVB induced a relatively larger extrusion force, tipping, and rotational moment on the molar due to the hook location changing from the end to the middle of the bar. These observations were consistent with the 3D stress distribution of the MSDs. The mechanical understanding from this work may shed light on the optimal design of MSDs. Full article
(This article belongs to the Special Issue Advances in Mechanics of Biomaterials)
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14 pages, 2784 KB  
Article
A New Digital Method to Quantify the Effects Produced by Carriere Motion Appliance
by Aldara Rosalía Nercellas Rodríguez, Pedro Colino Gallardo, Álvaro Zubizarreta-Macho, Carlos Colino Paniagua, Alfonso Alvarado Lorenzo and Alberto Albaladejo Martínez
J. Pers. Med. 2023, 13(5), 859; https://doi.org/10.3390/jpm13050859 - 20 May 2023
Cited by 2 | Viewed by 3182
Abstract
The aim of this study was to analyze a novel digital technique to quantify the distal tooth displacement and derotation angle produced by the Carriere Motion Appliance (CMA). Twenty-one patients with a class II molar and canine relationship underwent orthodontic treatment with CMA. [...] Read more.
The aim of this study was to analyze a novel digital technique to quantify the distal tooth displacement and derotation angle produced by the Carriere Motion Appliance (CMA). Twenty-one patients with a class II molar and canine relationship underwent orthodontic treatment with CMA. All patients were exposed before (STL1) and after the CMA placement (STL2), submitted to a digital impression, and afterwards, data were uploaded to specific cephalometric software to allow automatic mesh network alignment of the STL digital files. Subsequently, the distal tooth displacement of the upper canines and first upper molars, as well as the derotation angle of the first upper molars were analyzed using the Pearson correlation coefficient (ρ). Repeatability and reproducibility were analyzed using Gage R&R statistical analysis. An increase in canine displacement was correlated with an increase in contralateral canine displacement (ρ = 0.759; p < 0.000). An increase in canine displacement was correlated with an increase in molar displacement (ρ = 0.715; p < 0.001). An increase in upper first molar displacement was correlated with an increase in the contralateral upper first molar displacement (ρ = 0.609; p < 0.003) and the canine displacement (ρ = 0.728; p < 0.001). The distal tooth displacement showed a repeatability of 0.62% and reproducibility of 7.49%, and the derotation angle showed a repeatability of 0.30% and reproducibility of 0.12%. The novel digital measurement technique is a reproducible, repeatable, and accurate method for quantifying the distal tooth displacement of the upper canine and first upper molar, as well as the derotation angle of the first upper molars after using CMA. Full article
(This article belongs to the Special Issue Recent Advances in Dental Practice)
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23 pages, 17845 KB  
Article
Sulfide Trace Element Signatures and S- and Pb-Isotope Geochemistry of Porphyry Copper and Epithermal Gold-Base Metal Mineralization in the Elatsite–Chelopech Ore Field (Bulgaria)
by Elitsa Stefanova, Stoyan Georgiev, Irena Peytcheva, Peter Marchev, Albrecht von Quadt, Raya Raicheva, Ianko Gerdjikov, Kalin Kouzmanov, Adrian Boyce and Torsten Vennemann
Minerals 2023, 13(5), 630; https://doi.org/10.3390/min13050630 - 30 Apr 2023
Cited by 4 | Viewed by 4140
Abstract
The Elatsite–Chelopech ore field in the northern part of the Panagyurishte district in Central Bulgaria comprises numerous spatially associated porphyry copper and epithermal gold deposits and prospects. In addition to the mineralization and alteration features, trace elements, lead and sulfur isotope signatures of [...] Read more.
The Elatsite–Chelopech ore field in the northern part of the Panagyurishte district in Central Bulgaria comprises numerous spatially associated porphyry copper and epithermal gold deposits and prospects. In addition to the mineralization and alteration features, trace elements, lead and sulfur isotope signatures of sulfide minerals from porphyry copper, base metal and gold-base metal deposits/prospects have been studied. LA-ICP-MS analyses of pyrite, arsenopyrite and sulfosalt minerals validate them as major carriers for Au, Ag, Sb, Se and Co. Pyrite from the three types of mineralization has specific geochemical characteristics. Pyrite from the porphyry copper deposits/prospects has generally lower total trace element content compared to pyrite from the epithermal prospects, except for Se, Co and Ni. Pyrite from the base metal and gold-base metal veins is enriched in As, Au, Ag, Sb and Pb. In pyrite from the base metal deposits, Co and Ni have contents comparable to the pyrite from the porphyry copper deposits, while pyrite from the gold-base metal veins shows lower Co and Ni. Arsenopyrite from these deposits shows similar features. Similarly, sphalerite from the gold-base metal veins also has lower Co content compared to sphalerite from the base metal veins but higher In and Cu contents. In addition to the close spatial relationships between the Elatsite and Gorna Kamenitsa porphyry Cu deposits and Negarstitsa-West and Dolna Kamenitsa base metal prospects, as well as similarities in the mineralization and alteration styles, the lead isotopic (206Pb/204Pb = 18.61–18.68, 207Pb/204Pb = 15.64–15.65 for porphyry and 206Pb/204Pb = 18.55–18.67, 207Pb/204Pb = 15.64–15.68 for base metal) and sulfur isotopic (δ34S values of −3 to +1‰ for porphyry and δ34S values of −1.7 to +3.5‰ for base metal) signatures of sulfides support the idea of a genetic link between these two types of deposits. The porphyry and base-metal mineralization result from a common major ore-forming event during the Late Cretaceous, corresponding to deep/higher-temperature and shallower/distal/lower-temperature environments, respectively. In particular, more radiogenic lead (206Pb/204Pb = 18.41–18.47, 207Pb/204Pb = 15.67–15.76) and slightly different sulfur isotopic compositions (δ34S values of +3.5 to +10.6‰) of sulfides from the distal gold-base metal veins of Kordunsko Dere, Svishti Plaz and Shipkite might be a consequence of the interaction of the ore-forming fluids with an external older crustal and isotopically positive S source. Alternatively, a different fluid source/event for the formation of these gold-base metal veins may be suggested. Full article
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15 pages, 4127 KB  
Article
Cupriavidus necator-Produced Polyhydroxybutyrate/Eudragit FS Hybrid Nanoparticles Mitigates Ulcerative Colitis via Colon-Targeted Delivery of Cyclosporine A
by Juho Lee, Aruzhan Saparbayeva, Shwe Phyu Hlaing, Dongmin Kwak, Hyunwoo Kim, Jihyun Kim, Eun Hee Lee and Jin-Wook Yoo
Pharmaceutics 2022, 14(12), 2811; https://doi.org/10.3390/pharmaceutics14122811 - 15 Dec 2022
Cited by 9 | Viewed by 2380
Abstract
Polyhydroxybutyrate (PHB) has emerged as a novel material for replacing various plastics used in the medical field. However, its application as a drug-delivery carrier for colitis-targeted delivery has not been explored. In this study, we used biosynthesized PHB combined with Eudragit FS (EFS) [...] Read more.
Polyhydroxybutyrate (PHB) has emerged as a novel material for replacing various plastics used in the medical field. However, its application as a drug-delivery carrier for colitis-targeted delivery has not been explored. In this study, we used biosynthesized PHB combined with Eudragit FS (EFS) and cyclosporine A (CSA) to develop pH-responsive controlled CSA-releasing nanoparticles (CSA-PENPs) for colitis-targeted drug delivery and demonstrated its enhanced therapeutic efficacy in a dextran sulfate sodium (DSS)-induced murine colitis model. PHB was successfully biosynthesized in the bacterium Cupriavidus necator, as demonstrated by 1H-NMR and FT-IR analyses. CSA-PENPs were fabricated via the oil-in-water emulsion solvent evaporation method. Owing to the potent pH-responsive and sustained drug release properties provided by PHB and EFS, CSA-PENPs could deliver a sufficient amount of CSA to inflamed tissues in the distal colon; in contrast, CSA-loaded EFS nanoparticles displayed premature burst release before reaching the target site. Due to enhanced CSA delivery to colitis tissues, CSA-PENPs exhibited potent anti-inflammatory effects in the DSS-induced murine colitis model. Overall, CSA-PENPs could be a promising drug-delivery system for treating ulcerative colitis. Full article
(This article belongs to the Special Issue Transforming Textbook Concepts into Novel Drug Delivery Systems)
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22 pages, 5236 KB  
Article
In Vitro and In Vivo Evaluation of Hydroxypropyl-β-cyclodextrin-grafted-poly(acrylic acid)/poly(vinyl pyrrolidone) Semi-Interpenetrating Matrices of Dexamethasone Sodium Phosphate
by Nyla Ajaz, Anum Abbas, Rabia Afshan, Muhammad Irfan, Syed Haroon Khalid, Sajid Asghar, Muhammad Usman Munir, Waleed Y. Rizg, Kamlah Ali Majrashi, Sameer Alshehri, Mohammed Alissa, Mohammed Majrashi, Deena M. Bukhary, Ghulam Hussain, Fauzia Rehman and Ikram Ullah Khan
Pharmaceuticals 2022, 15(11), 1399; https://doi.org/10.3390/ph15111399 - 14 Nov 2022
Cited by 9 | Viewed by 3691
Abstract
In this paper, we fabricated semi-interpenetrating polymeric network (semi-IPN) of hydroxypropyl-β-cyclodextrin-grafted-poly(acrylic acid)/poly(vinyl pyrrolidone) (HP-β-CD-g-poly(AA)/PVP) by the free radical polymerization technique, intended for colon specific release of dexamethasone sodium phosphate (DSP). Different proportions of polyvinyl pyrrolidone (PVP), acrylic acid (AA), and hydroxypropyl-beta-cyclodextrin [...] Read more.
In this paper, we fabricated semi-interpenetrating polymeric network (semi-IPN) of hydroxypropyl-β-cyclodextrin-grafted-poly(acrylic acid)/poly(vinyl pyrrolidone) (HP-β-CD-g-poly(AA)/PVP) by the free radical polymerization technique, intended for colon specific release of dexamethasone sodium phosphate (DSP). Different proportions of polyvinyl pyrrolidone (PVP), acrylic acid (AA), and hydroxypropyl-beta-cyclodextrin (HP-β-CD) were reacted along with ammonium persulphate (APS) as initiator and methylene-bis-acrylamide (MBA) as crosslinker to develop a hydrogel system with optimum swelling at distal intestinal pH. Initially, all formulations were screened for swelling behavior and AP-8 was chosen as optimum formulation. This formulation was capable of releasing a small amount of drug at acidic pH (1.2), while a maximum amount of drug was released at colonic pH (7.4) by the non-Fickian diffusion mechanism. Fourier transformed infrared spectroscopy (FTIR) revealed successful grafting of components and development of semi-IPN structure without any interaction with DSP. Thermogravimetric analysis (TGA) confirmed the thermal stability of developed semi-IPN. X-ray diffraction (XRD) revealed reduction in crystallinity of DSP upon loading in the hydrogel. The scanning electron microscopic (SEM) images revealed a rough and porous hydrogel surface. The toxicological evaluation of semi-IPN hydrogels confirmed their bio-safety and hemocompatibility. Therefore, the prepared hydrogels were pH sensitive, biocompatible, showed good swelling, mechanical properties, and were efficient in releasing the drug in the colonic environment. Therefore, AP-8 can be deemed as a potential carrier for targeted delivery of DSP to treat inflammatory bowel diseases. Full article
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8 pages, 776 KB  
Article
Quantitative Sensory Testing in Late-Onset ATTRv Presymptomatic Subjects: A Single Center Experience
by Stefano Tozza, Daniele Severi, Giovanni Palumbo, Vincenzo Provitera, Lucia Ruggiero, Raffaele Dubbioso, Rosa Iodice, Maria Nolano and Fiore Manganelli
Biomedicines 2022, 10(11), 2877; https://doi.org/10.3390/biomedicines10112877 - 10 Nov 2022
Cited by 11 | Viewed by 1948
Abstract
Backgrounds Hereditary transthyretin amyloidosis (ATTRv) presymptomatic subjects undergo multidisciplinary evaluation to detect, as early as possible, a subclinical involvement of multisystem disease. Quantitative sensory testing (QST) that investigates and discriminates the function of C, Aδ and Aβ fibers is included as an instrumental [...] Read more.
Backgrounds Hereditary transthyretin amyloidosis (ATTRv) presymptomatic subjects undergo multidisciplinary evaluation to detect, as early as possible, a subclinical involvement of multisystem disease. Quantitative sensory testing (QST) that investigates and discriminates the function of C, Aδ and Aβ fibers is included as an instrumental test to monitor nerve fiber function. The purpose of this study was to evaluate the role of QST in the context of the multidisciplinary evaluation in late onset carriers. Methods Four-teen presymptomatic (namely carriers) were enrolled. Subjects underwent thermal [cold and warm detection threshold (CDT, WDT), cold and heat pain (CP and HP)] and tactile QST in four body sites: foot dorsum, distal lateral leg, distal thigh, hand dorsum. Results Overall, presymptomatic subject showed a significant difference in all thermal QST findings compared to the control group. All subjects had at least one altered thermal QST finding; the sites more frequently altered were foot and leg, whilst the thermal modalities which were more frequently abnormal were CDT, WDT and CP. Conclusions Our study highlights the importance of performing thermal QST in subjects carrying TTR mutation, given the high frequency of abnormal findings. Notably, performing both innocuous and painful stimulation in foot and/or leg increases the chance of detecting nerve fiber dysfunction. Moreover, the investigation of the hand may provide useful information in monitoring disease progression before the Predicted Age of Disease Onset (PADO). Full article
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13 pages, 2151 KB  
Article
Molecular Cytogenetic Characterization of Novel 1RS.1BL Translocation and Complex Chromosome Translocation Lines with Stripe Rust Resistance
by Zhi Li, Zhenglong Ren, Feiquan Tan, Peigao Luo and Tianheng Ren
Int. J. Mol. Sci. 2022, 23(5), 2731; https://doi.org/10.3390/ijms23052731 - 1 Mar 2022
Cited by 6 | Viewed by 2420
Abstract
Rye is the most important source for the genetic improvement of wheat. In this study, two stable wheat-rye primary 1RS.1BL translocation lines, RT855-13 and RT855-14, were selected and identified by acid polyacrylamide gel electrophoresis (A-PAGE), co-dominant PCR, and multi-color fluorescence in situ hybridization [...] Read more.
Rye is the most important source for the genetic improvement of wheat. In this study, two stable wheat-rye primary 1RS.1BL translocation lines, RT855-13 and RT855-14, were selected and identified by acid polyacrylamide gel electrophoresis (A-PAGE), co-dominant PCR, and multi-color fluorescence in situ hybridization (MC-FISH) from the progeny of the crossing of the wheat cultivar Mianyang11 and a Chinese rye Weining. When more than two independent, simple reciprocal translocations are involved in a carrier, they are defined as complex chromosome translocations (CCT). The MC-FISH results also indicated that CCT occurred in RT855-13; namely that, besides 1RS.1BL translocation chromosomes, there are other two pairs of balanced reciprocal translocations. It was demonstrated that the interchange between a distal segment of 4B and long arm of 3D occurred in the RT855-13. The novel translocation chromosomes in wheat were recorded as 3DS.4BSDS and 3DL-4BSPS.4BL. Reports about CCT as a genetic resource in plant breeding programs are scarce. Both lines expressed high resistance to Puccinia striiformis f. sp. tritici, which are prevalent in China and are virulent on Yr9, and the CCT line RT855-13 retained better resistance as adult plants compared with RT855-14 in the field. Both lines, especially the CCT line RT855-13, exhibited better agronomic traits than their wheat parent, Mianyang11, indicating that both translocation lines could potentially be used for wheat improvement. The results also indicated that the position effects of CCT can lead to beneficial variations in agronomic and resistant traits, making them a valuable genetic resource to wheat breeding programs. Full article
(This article belongs to the Special Issue Genetics and Breeding of Wheat)
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