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Advanced Science (Weinheim,... Sep 2023Cartilage damage affects millions of people worldwide. Tissue engineering strategies hold the promise to provide off-the-shelf cartilage analogs for tissue...
Cartilage damage affects millions of people worldwide. Tissue engineering strategies hold the promise to provide off-the-shelf cartilage analogs for tissue transplantation in cartilage repair. However, current strategies hardly generate sufficient grafts, as tissues cannot maintain size growth and cartilaginous phenotypes simultaneously. Herein, a step-wise strategy is developed for fabricating expandable human macromass cartilage (macro-cartilage) in a 3D condition by employing human polydactyly chondrocytes and a screen-defined serum-free customized culture (CC). CC-induced chondrocytes demonstrate improved cell plasticity, expressing chondrogenic biomarkers after a 14.59-times expansion. Crucially, CC-chondrocytes form large-size cartilage tissues with average diameters of 3.25 ± 0.05 mm, exhibiting abundant homogenous matrix and intact structure without a necrotic core. Compared with typical culture, the cell yield in CC increases 2.57 times, and the expression of cartilage marker collagen type II increases 4.70 times. Transcriptomics reveal that this step-wise culture drives a proliferation-to-differentiation process through an intermediate plastic stage, and CC-chondrocytes undergo a chondral lineage-specific differentiation with an activated metabolism. Animal studies show that CC macro-cartilage maintains a hyaline-like cartilage phenotype in vivo and significantly promotes the healing of large cartilage defects. Overall, an efficient expansion of human macro-cartilage with superior regenerative plasticity is achieved, providing a promising strategy for joint regeneration.
Topics: Animals; Humans; Cartilage, Articular; Chondrocytes; Tissue Engineering; Cell Differentiation; Regeneration
PubMed: 37395375
DOI: 10.1002/advs.202301833 -
Cureus Jul 2023Hyperthyroidism is more common in women and the sensitivity of thyroid function changes during pregnancy. Excess levels of thyroid hormones and thioamides have a major... (Review)
Review
Hyperthyroidism is more common in women and the sensitivity of thyroid function changes during pregnancy. Excess levels of thyroid hormones and thioamides have a major impact on maternal and fetal outcomes. Our aim was to perform an extensive literature review and provide relevant details concerning the analytical and clinical aspects of the potential effects of the two main drugs used (methimazole and propylthiouracil) in newborns. A thorough literature review was conducted using PubMed and Google Scholar databases. In total, 10 relevant studies were identified and data from these studies were extracted and then extrapolated into results after analysis. Three out of four studies that used methimazole and carbimazole, one and two, respectively, showed adverse fetal outcomes requiring surgical management for congenital anomalies like aplasia cutis, patent vitellointestinal duct, and gastroschisis. Out of the three studies that used propylthiouracil, one baby underwent surgery for bilateral pyelectasis, vesicovaginal fistula, anal stenosis, and polydactyly. The findings of the aforementioned studies provide enough evidence to imply that the use of methimazole and carbimazole to treat antenatal hyperthyroidism has worse fetal outcomes than the use of propylthiouracil. Also, given the paucity of data in the existing literature regarding propylthiouracil's effects on newborns, further studies in this demographic are needed.
PubMed: 37551246
DOI: 10.7759/cureus.41505 -
Cureus Apr 2024Polydactyly-myopia syndrome is a rare genetic condition characterized by the co-occurrence of polydactyly and myopia. Herein, we present the case of a 28-year-old Muslim...
Polydactyly-myopia syndrome is a rare genetic condition characterized by the co-occurrence of polydactyly and myopia. Herein, we present the case of a 28-year-old Muslim male, born of consanguineous parents, who presented with complaints of diminished vision since childhood. Ophthalmologic examination revealed severe myopia with characteristic fundus changes indicative of high myopia. Additionally, the patient exhibited polydactyly in all limbs, with a positive family history of both polydactyly and myopia. This case underscores the importance of recognizing and managing rare syndromes to provide appropriate genetic counseling and clinical care. Further research is warranted to elucidate the underlying genetic mechanisms and optimize therapeutic strategies for polydactyly-myopia syndrome. Awareness of this syndrome among healthcare providers is essential to facilitate early diagnosis and intervention for affected individuals and their families.
PubMed: 38745815
DOI: 10.7759/cureus.58235 -
The Journal of Hand Surgery, European... Dec 2023Ulnar dimelia is a very rare unilateral congenital upper limb anomaly (CULA) affecting the whole extremity. Treatment remains difficult because of the complexity and... (Review)
Review
Ulnar dimelia is a very rare unilateral congenital upper limb anomaly (CULA) affecting the whole extremity. Treatment remains difficult because of the complexity and multi-level involvement. Twenty-four cases with duplicated ulna, absent radius and polydactyly from seven European centres were reviewed according to a structured list of parameters. At first consultation, median age 8 months (1-178), the shoulder movement was good in 17 patients or poor in six, and the median passive elbow range of motion was 20° (0°-90°). The resting wrist position was flexed in 22/24 patients. Following stretching and splinting, elbow surgery included resection of the lateral proximal ulna in 11 patients and muscle transfers in six to improve passive movement and increase active elbow motion, respectively. Tendon transfers were performed in eight wrists and a pollicization or pseudo-pollicization in 23 patients. Overall, patients demonstrate acceptable function postoperatively. Guidelines for treatment of this severe CULA are presented. IV.
Topics: Humans; Hand Deformities, Congenital; Ulna; Polydactyly; Wrist Joint; Upper Extremity; Radius
PubMed: 37684016
DOI: 10.1177/17531934231196418 -
Neurology India 2023
Topics: Child; Humans; Polydactyly; Seizures
PubMed: 37929493
DOI: 10.4103/0028-3886.388066 -
Frontiers in Endocrinology 2023Primary cilia are microtubule-based organelles that are widespread on the cell surface and play a key role in tissue development and homeostasis by sensing and... (Review)
Review
Primary cilia are microtubule-based organelles that are widespread on the cell surface and play a key role in tissue development and homeostasis by sensing and transducing various signaling pathways. The process of intraflagellar transport (IFT), which is propelled by kinesin and dynein motors, plays a crucial role in the formation and functionality of cilia. Abnormalities in the cilia or ciliary transport system often cause a range of clinical conditions collectively known as ciliopathies, which include polydactyly, short ribs, scoliosis, thoracic stenosis and many abnormalities in the bones and cartilage. In this review, we summarize recent findings on the role of primary cilia and ciliary transport systems in bone development, we describe the role of cilia in bone formation, cartilage development and bone resorption, and we summarize advances in the study of primary cilia in fracture healing. In addition, the recent discovery of crosstalk between integrins and primary cilia provides new insights into how primary cilia affect bone.
Topics: Cilia; Flagella; Biological Transport; Kinesins; Dyneins
PubMed: 37886641
DOI: 10.3389/fendo.2023.1259650 -
PLoS Biology Dec 2023Ciliopathies are associated with wide spectrum of structural birth defects (SBDs), indicating important roles for cilia in development. Here, we provide novel insights...
Ciliopathies are associated with wide spectrum of structural birth defects (SBDs), indicating important roles for cilia in development. Here, we provide novel insights into the temporospatial requirement for cilia in SBDs arising from deficiency in Ift140, an intraflagellar transport (IFT) protein regulating ciliogenesis. Ift140-deficient mice exhibit cilia defects accompanied by wide spectrum of SBDs including macrostomia (craniofacial defects), exencephaly, body wall defects, tracheoesophageal fistula (TEF), randomized heart looping, congenital heart defects (CHDs), lung hypoplasia, renal anomalies, and polydactyly. Tamoxifen inducible CAGGCre-ER deletion of a floxed Ift140 allele between E5.5 to 9.5 revealed early requirement for Ift140 in left-right heart looping regulation, mid to late requirement for cardiac outflow septation and alignment, and late requirement for craniofacial development and body wall closure. Surprisingly, CHD were not observed with 4 Cre drivers targeting different lineages essential for heart development, but craniofacial defects and omphalocele were observed with Wnt1-Cre targeting neural crest and Tbx18-Cre targeting epicardial lineage and rostral sclerotome through which trunk neural crest cells migrate. These findings revealed cell autonomous role of cilia in cranial/trunk neural crest-mediated craniofacial and body wall closure defects, while non-cell autonomous multi-lineage interactions underlie CHD pathogenesis, revealing unexpected developmental complexity for CHD associated with ciliopathies.
Topics: Animals; Mice; Cilia; Heart Defects, Congenital; Embryonic Development; Carrier Proteins; Skull; Ciliopathies
PubMed: 38079449
DOI: 10.1371/journal.pbio.3002425 -
BMC Medical Genomics Dec 2023Short-rib polydactyly syndrome (SRPS) refers to a group of lethal skeletal dysplasias that can be difficult to differentiate between subtypes or from other non-lethal...
BACKGROUND
Short-rib polydactyly syndrome (SRPS) refers to a group of lethal skeletal dysplasias that can be difficult to differentiate between subtypes or from other non-lethal skeletal dysplasias such as Ellis-van Creveld syndrome and Jeune syndrome in a prenatal setting. We report the ultrasound and genetic findings of four unrelated fetuses with skeletal dysplasias.
METHODS
Systemic prenatal ultrasound examination was performed in the second or third trimester. Genetic tests including GTG-banding, single nucleotide polymorphism (SNP) array and exome sequencing were performed with amniocytes or aborted fetal tissues.
RESULTS
The major and common ultrasound anomalies for the four unrelated fetuses included short long bones of the limbs and narrow thorax. No chromosomal abnormalities and pathogenic copy number variations were detected. Exome sequencing revealed three novel variants in the DYNC2H1 gene, namely NM_001080463.2:c.6809G > A p.(Arg2270Gln), NM_001080463.2:3133C > T p.(Gln1045Ter), and NM_001080463.2:c.337C > T p.(Arg113Trp); one novel variant in the IFT172 gene, NM_015662.3:4540-5 T > A; and one novel variant in the WDR19 gene, NM_025132.4:c.2596G > C p.(Gly866Arg). The genotypes of DYNC2H1, IFT172 and WDR19 and the phenotypes of the fetuses give hints for the diagnosis of short-rib thoracic dysplasia (SRTD) with or without polydactyly 3, 10, and 5, respectively.
CONCLUSION
Our findings expand the mutation spectrum of DYNC2H1, IFT172 and WDR19 associated with skeletal ciliopathies, and provide useful information for prenatal diagnosis and genetic counseling on rare skeletal disorders.
Topics: Pregnancy; Female; Humans; DNA Copy Number Variations; Ellis-Van Creveld Syndrome; Prenatal Diagnosis; Osteochondrodysplasias; Polydactyly; Ciliopathies; Cytoskeletal Proteins; Adaptor Proteins, Signal Transducing
PubMed: 38062428
DOI: 10.1186/s12920-023-01753-y -
Cureus Oct 2023Laurence-Moon-Bardet Biedl syndrome (LMBBS) is a rare autosomal recessive genetic disorder that is most frequently found in children born from consanguineous marriages....
Laurence-Moon-Bardet Biedl syndrome (LMBBS) is a rare autosomal recessive genetic disorder that is most frequently found in children born from consanguineous marriages. The most prominent clinical characteristics of this syndrome include rod and cone dystrophy, nystagmus, central obesity, polydactyly, hypogonadism in males, renal anomalies, developmental delay, ataxia, speech difficulties, and poor coordination. In this report, we describe the case of a 31-year-old male who had the classical clinical features of LMBBS like developmental delay, retinitis pigmentosa, nystagmus, obesity, hypogonadism, and central obesity, presenting with abdominal pain associated with vomiting and tenderness in the right lower quadrant. The patient was diagnosed with cholelithiasis. This case report emphasizes the atypical complication of cholelithiasis due to the underlying syndrome and the need for further research in this area.
PubMed: 38021809
DOI: 10.7759/cureus.47316 -
JPRAS Open Dec 2023Thumb triplication is a very rare pattern of radial polydactyly that presents as a more complicated form of thumb. Because of its morphological complexity, treatment...
Thumb triplication is a very rare pattern of radial polydactyly that presents as a more complicated form of thumb. Because of its morphological complexity, treatment often requires surgical ingenuity in addition to the conventional surgical treatment algorithms for duplication. We report the case of thumb triplication on the right hand of a 17-month-old boy. We performed on-top-plasty of the ulnar thumb over the intermediate thumb, and achieved a functional and aesthetic thumb. The technique of on-top-plasty is effective for finger reconstruction that maximizes the use of limited tissue and is widely used for treating hand trauma and congenital hand anomalies. In the present case, on-top-plasty contributed most effectively to creating a sufficiently sized thumb, achieving interphalangeal optimization by joining the extra middle phalanx with the proximal phalanx, and securing the first web space by moving the ulnar thumb laterally.
PubMed: 37675276
DOI: 10.1016/j.jpra.2023.08.007