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PloS One 2023The purpose of this study was to examine the efficacy of ICG-mediated fluorescence molecular imaging (FMI) in debridement of necrotic tissue. 96 wound-infected rats were...
The purpose of this study was to examine the efficacy of ICG-mediated fluorescence molecular imaging (FMI) in debridement of necrotic tissue. 96 wound-infected rats were randomly divided into control group, ICG group, excitation light (EL)group and FMI group for debridement of necrotic tissue (n = 24). (I) Control group: only debridement; (II) ICG group: ICG injection before debridement; (III) EL group: Debridement under EL; (IV) FMI group: Debridement guided by ICG-mediated FMI. On the 3rd, 6th, and 9th days, the wound tissues of the rats in each group were collected for histological examination, and the levels of serum interleukin-4 (IL-4) and interferon-γ (INF-γ) were analyzed. The wound healing rate, wound score and body weight of the rats in each group were followed up until the wound healed. The results showed that the infected wounds of the rats in the FMI group had significant fluorescence development. The level of serum IL-4 in the FMI group was higher than that in the other three groups on the 6th day (p<0.01), while the level of INF-γ was lower than that in the other three groups on the 6th and 9th day (p<0.05). The results of dynamic wound tissue H&E staining indicated that the wound healing in the FMI group was better than the other three groups. The in vivo follow-up results showed that the wound healing rate and wound score of the FMI group were better than the other three groups, and the growth of rats had no difference with the other groups. ICG-mediated FMI can achieve accurate imaging of necrotic tissue for debridement, and so can accelerate wound healing, which has good clinical application prospects.
Topics: Animals; Rats; Debridement; Interleukin-4; Body Weight; Control Groups; Interferon-gamma; Necrosis; Wound Healing
PubMed: 37733658
DOI: 10.1371/journal.pone.0291508 -
The Journal of Clinical Endocrinology... Nov 2023Children exposed to gestational diabetes mellitus (GDM) in utero are at high risk of developing overweight and obesity, but their postnatal growth trajectories and risk...
CONTEXT
Children exposed to gestational diabetes mellitus (GDM) in utero are at high risk of developing overweight and obesity, but their postnatal growth trajectories and risk profiles remain unclear.
OBJECTIVE
We aimed to identify distinct body mass index (BMI) trajectories from birth to 10 years of age in children exposed to GDM and to explore their associations with infant and maternal characteristics.
METHODS
This nationwide cohort study linked data from Danish registries on 15 509 children exposed to GDM in utero, born in Denmark from January 2008 to October 2019. We applied latent class trajectory modeling to identify distinct BMI trajectories. Associations of BMI trajectories with infant and maternal characteristics were analyzed using multiple linear regression.
RESULTS
We identified 3 distinct BMI trajectories characterized by a "normal" (60%), a "late accelerating" (28%) and an "early accelerating" (12%) BMI trajectory, the 2 latter at risk of overweight and obesity, respectively, at age 10 years, relative to World Health Organization child growth standards. Children in the "late accelerating" BMI trajectory were more often born large for gestational age (P < .001). More children in the "early accelerating" BMI trajectory were boys, born small for gestational age, and had mothers with a higher pre-pregnancy BMI compared to the other groups (P < .001).
CONCLUSION
Children exposed to GDM in utero differ widely in their BMI trajectory. The detection of risk profiles based on early BMI growth and infant and maternal characteristics provides an opportunity for future targeted care and prevention.
Topics: Pregnancy; Infant; Male; Female; Child; Humans; Diabetes, Gestational; Body Mass Index; Overweight; Cohort Studies; Birth Weight; Risk Factors; Obesity; Mothers
PubMed: 37379575
DOI: 10.1210/clinem/dgad384 -
Advanced Drug Delivery Reviews Nov 2023Over the past few years, the adoption of machine learning (ML) techniques has rapidly expanded across many fields of research including formulation science. At the same... (Review)
Review
Over the past few years, the adoption of machine learning (ML) techniques has rapidly expanded across many fields of research including formulation science. At the same time, the use of lipid nanoparticles to enable the successful delivery of mRNA vaccines in the recent COVID-19 pandemic demonstrated the impact of formulation science. Yet, the design of advanced pharmaceutical formulations is non-trivial and primarily relies on costly and time-consuming wet-lab experimentation. In 2021, our group published a review article focused on the use of ML as a means to accelerate drug formulation development. Since then, the field has witnessed significant growth and progress, reflected by an increasing number of studies published in this area. This updated review summarizes the current state of ML directed drug formulation development, introduces advanced ML techniques that have been implemented in formulation design and shares the progress on making self-driving laboratories a reality. Furthermore, this review highlights several future applications of ML yet to be fully exploited to advance drug formulation research and development.
Topics: Humans; Drug Compounding; Pandemics; Machine Learning
PubMed: 37774977
DOI: 10.1016/j.addr.2023.115108 -
Metabolic Engineering Mar 2024Precise control over mammalian cell growth dynamics poses a major challenge in biopharmaceutical manufacturing. Here, we present a multi-level cell engineering strategy...
Precise control over mammalian cell growth dynamics poses a major challenge in biopharmaceutical manufacturing. Here, we present a multi-level cell engineering strategy for the tunable regulation of growth phases in mammalian cells. Initially, we engineered mammalian death phase by employing CRISPR/Cas9 to knockout pro-apoptotic proteins Bax and Bak, resulting in a substantial attenuation of apoptosis by improving cell viability and extending culture lifespan. The second phase introduced a growth acceleration system, akin to a "gas pedal", based on an abscidic acid inducible system regulating cMYC gene expression, enabling rapid cell density increase and cell cycle control. The third phase focused on a stationary phase inducing system, comparable to a "brake pedal". A tetracycline inducible genetic circuit based on BLIMP1 gene led to cell growth cessation and arrested cell cycle upon activation. Finally, we developed a dual controllable system, combining the "gas and brake pedals", enabling for dynamic and precise orchestration of mammalian cell growth dynamics. This work exemplifies the application of synthetic biology tools and combinatorial cell engineering, offering a sophisticated framework for manipulating mammalian cell growth and providing a unique paradigm for reprogramming cell behaviour for enhancing biopharmaceutical manufacturing and further biomedical applications.
Topics: Cell Division; Gene Regulatory Networks; Biological Products; CRISPR-Cas Systems; Genetic Engineering; Cell Engineering
PubMed: 38325641
DOI: 10.1016/j.ymben.2024.01.006 -
Aging Dec 2023Response to oncogenic factors like UV, GADD45 family in skin participates in scavenging ROS, DNA repair and cell cycle control. Because of this, the previous study of...
Response to oncogenic factors like UV, GADD45 family in skin participates in scavenging ROS, DNA repair and cell cycle control. Because of this, the previous study of the chronic UVB injury model has found that hsa-miR-300 can conduct intercellular transport by exosomes and target regulation of GADD45B. Whether the hsa-miR-300-GADD45B still regulates tumor development by cell cycle pathway is unclear. Through transcriptomic analysis of primary (n=39) and metastatic (n=102) melanoma, it was confirmed that in metastatic samples, some of the 97 down-regulated genes participate in maintaining skin homeostasis while 42 up-regulated genes were enriched in cancer-related functions. Furthermore, CDKN1A, CDKN2A, CXCR4 and RAD51 in the melanoma pathway, were also differentially expressed between normal skin and melanoma. CDKN1A and CDKN2A were also found to be involved in TP53-dependent cell cycle regulation. In conclusion, it was speculated that CDKN1A, CDKN2A, TP53, GADD45B and hsa-miR-300 may have regulatory relationships. It was demonstrated that there is a bidirectional regulation between hsa-miR-300 and TP53. In addition, miR-300 can regulate CDKN1A by GADD45B/TP53 and promote melanoma growth by accelerating the cell cycle transition from G1/S to G2 phase.
Topics: Humans; Melanoma; Cell Cycle; MicroRNAs; Cell Division; Cell Cycle Checkpoints; GADD45 Proteins; Antigens, Differentiation
PubMed: 38070141
DOI: 10.18632/aging.205276 -
The Journal of Clinical Endocrinology... Sep 2023Since the initial outbreak of coronavirus disease 2019 (COVID-19), a novel population of children with in utero exposure to maternal infection has emerged whose health...
CONTEXT
Since the initial outbreak of coronavirus disease 2019 (COVID-19), a novel population of children with in utero exposure to maternal infection has emerged whose health outcomes are largely unknown.
OBJECTIVE
To compare longitudinal growth trajectories among infants with vs without in utero COVID-19 exposure.
METHODS
We conducted a longitudinal cohort study leveraging a prospectively enrolled perinatal biorepository among 149 infants with in utero COVID-19 exposure and 127 unexposed controls. Weight, length, and body mass index (BMI) were abstracted from health records at 0, 2, 6, and 12 months and standardized using World Health Organization growth charts. Analyses were adjusted for maternal age, ethnicity, parity, insurance, and BMI as well as infant sex, birthdate, and breastfeeding.
RESULTS
Infants with in utero COVID-19 exposure vs controls exhibited differential trajectories of weight and BMI, but not length, z-score over the first year of life (study group × time interaction, P < .0001 for weight and BMI). Infants born to mothers with prenatal COVID-19 had lower BMI z-score at birth (effect size: -0.35, 95% CI -0.66 to -0.03) and greater gain in BMI z-score from birth to 12 months (effect size: 0.53, 95% CI 0.06 to 0.99). Birth weight z-score mediated a significant proportion of the relationship between COVID-19 exposure and postnatal growth (estimate ± SE, 32 ± 14%, P = .02).
CONCLUSION
Infants with in utero COVID-19 exposure exhibited lower birth weight and accelerated weight gain in the first year of life, which may be harbingers of downstream cardiometabolic pathology. Further studies are needed to delineate cardiometabolic sequelae among this emerging global population.
Topics: Infant, Newborn; Child; Female; Pregnancy; Infant; Humans; Longitudinal Studies; Birth Weight; COVID-19; Weight Gain; Body Mass Index; Cardiovascular Diseases
PubMed: 36988326
DOI: 10.1210/clinem/dgad130 -
Public Health Nutrition Dec 2023To describe breastfeeding rates from early to late infancy and to examine associations between breastfeeding duration and infant growth, including rapid weight gain...
OBJECTIVE
To describe breastfeeding rates from early to late infancy and to examine associations between breastfeeding duration and infant growth, including rapid weight gain (RWG, > 0·67 SD increase in weight-for-age -score), among infants from low-income, racially and ethnically diverse backgrounds.
DESIGN
A short, prospective cohort study was conducted assessing breastfeeding status at infant ages 2, 4, 6, 9 and 12 months. Infant length and weight measurements were retrieved from electronic health records to calculate weight-for-length -scores and the rate of weight gain.
SETTING
Pediatric clinic in the Southeastern USA.
PARTICIPANTS
Mother-infant dyads ( = 256).
RESULTS
Most participants were African American (48 %) or Latina (34 %). Eighty-one per cent were participating in the Special Supplemental Nutrition Program for Women, Infants and Children. Infants were breastfed for a median duration of 4·75 months, with partial more common than exclusive breastfeeding. At 12 months, 28 % of the participants were breastfeeding. Infants breastfed beyond 6 months had significantly lower growth trajectories than infants breastfed for 0-2 months ( = 0·045, se = 0·013, = 0·001) or 3-6 months ( = 0·054, se = 0·016, = 0·001). Thirty-six per cent of the infants experienced RWG. RWG was more common among infants who were breastfed for 2 months or less than 6+ month breastfed group (relative risk = 1·68, CI (1·03, 2·74), = 0·03).
CONCLUSIONS
Breastfeeding beyond 6 months is associated with the prevention of accelerated growth among infants from low-income, racially and ethnically diverse backgrounds, suggesting progress toward health equity.
Topics: Infant; Child; Female; Humans; Breast Feeding; Prospective Studies; Weight Gain; Nutritional Status; Mothers
PubMed: 38047374
DOI: 10.1017/S1368980023002689 -
Journal of Endodontics Dec 2023Osteolectin is a secreted glycoprotein of the C-type lectin domain superfamily, expressed in bone tissues and is reported as a novel osteogenic factor that promotes bone...
INTRODUCTION
Osteolectin is a secreted glycoprotein of the C-type lectin domain superfamily, expressed in bone tissues and is reported as a novel osteogenic factor that promotes bone regeneration. However, the effect of osteolectin on human dental pulp cells (hDPCs) has not been reported. Therefore, we aimed to investigate the odontoblastic differentiation of osteolectin in hDPCs and further attempt to reveal its underlying mechanism.
METHODS
Cytotoxicity assays were used to detect the cytotoxicity of osteolectin. The odontoblastic differentiation of hDPCs and its underlying mechanisms were measured by the alkaline phosphatase (ALP) activity, mineralized spots formation, and the gene and protein expression of odontoblastic differentiation through ALP staining, Alizarin red S staining, quantitative real-time polymerase chain reaction, and Western blot analysis, respectively.
RESULTS
WST-1 assay showed osteolectin at concentrations below 300 ng/ml was noncytotoxic and safe for hDPCs. The following experiment demonstrated that osteolectin could increase ALP activity, accelerate the mineralization process, and up-regulate the odontogenic differentiation markers in both gene and protein levels (P < .05). Osteolectin stimulated the phosphorylation of ERK, JNK, and Protein kinase B (AKT) in hDPCs. Extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK), and AKT inhibitors decreased ALP activity and mineralization capacity and suppressed the expression of dentin sialophosphoprotein and dentin matrix protein-1.
CONCLUSION
Osteolectin can promote odontoblastic differentiation of hDPCs, and the whole process may stimulate ERK, JNK, and AKT signaling pathways by increasing p-ERK, p-JNK, and p-AKT signals.
Topics: Humans; Proto-Oncogene Proteins c-akt; Extracellular Matrix Proteins; Dental Pulp; Cell Differentiation; Signal Transduction; Odontoblasts; Alkaline Phosphatase; Cells, Cultured; Cell Proliferation; Phosphoproteins
PubMed: 37774945
DOI: 10.1016/j.joen.2023.09.010 -
Journal of Experimental & Clinical... Dec 2023Hedgehog-Gli1 signaling induces development of two common neurological features seen in pancreatic ductal adenocarcinoma (PDAC): peripheral neural invasion (PNI) and...
BACKGROUND
Hedgehog-Gli1 signaling induces development of two common neurological features seen in pancreatic ductal adenocarcinoma (PDAC): peripheral neural invasion (PNI) and peripheral neural remodeling (PNR). However, the underlying molecular mechanisms in cancer cells and nerves within Gli1-derived PNR have not previously been comprehensively analyzed.
METHODS
In this study, RNA sequencing was used to screen meaningful circRNAs in PNR. An in vitro model of PNR was subsequently constructed through a co-culture system comprising PDAC cells and murine dorsal root ganglia (DRG) (as the neuronal element), and the relevant mechanisms were explored using a series of molecular biology experiments. A subcutaneous nude mouse tumorigenesis model was established to further verify the occurrence of PNR that was detected in human PDAC samples.
RESULTS
We first confirmed the molecular mechanisms of PNR development through crosstalk between exosomal circ-0011536 and DRG. In Gli1-overpressed PDAC, circ-0011536 is mainly secreted by exosomes. After being ingested by DRG, it can promote the activity of DRG by degrading miR-451a and upregulating the expression of VGF. Overexpression of Gli1 can accelerate the proliferation of subcutaneous tumors in mice and is closely related to the density of nerve plexuses, while downregulating circ-RNA inhibits tumor proliferation and reduces the density of nerve plexuses. In addition, TMA results confirmed that Gli1 overexpression significantly increased the expression of VGF and was closely associated with increased nerve plexus density.
CONCLUSION
Hedgehog-Gli1-induced exosomal circ-0011536 promoted PNR via the miR-451a/VGF axis, thereby establishing that it may contribute to PDAC-associated nerve changes with activated Hedgehog signaling.
Topics: Humans; Mice; Animals; MicroRNAs; Hedgehog Proteins; Zinc Finger Protein GLI1; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Cell Proliferation; Cell Line, Tumor; Nerve Growth Factors
PubMed: 38041128
DOI: 10.1186/s13046-023-02894-9 -
JCI Insight Nov 2023Osteogenesis imperfecta (OI), or brittle bone disease, is a disorder characterized by bone fragility and increased fracture incidence. All forms of OI also feature short...
Osteogenesis imperfecta (OI), or brittle bone disease, is a disorder characterized by bone fragility and increased fracture incidence. All forms of OI also feature short stature, implying an effect on endochondral ossification. Using the Aga2+/- mouse, which has a mutation in type I collagen, we show an affected growth plate primarily due to a shortened proliferative zone. We used single-cell RNA-Seq analysis of tibial and femoral growth plate tissues to understand transcriptional consequences on growth plate cell types. We show that perichondrial cells, which express abundant type I procollagen, and growth plate chondrocytes, which were found to express low amounts of type I procollagen, had ER stress and dysregulation of the same unfolded protein response pathway as previously demonstrated in osteoblasts. Aga2+/- proliferating chondrocytes showed increased FGF and MAPK signaling, findings consistent with accelerated differentiation. There was also increased Sox9 expression throughout the growth plate, which is expected to accelerate early chondrocyte differentiation but reduce late hypertrophic differentiation. These data reveal that mutant type I collagen expression in OI has an impact on the cartilage growth plate. These effects on endochondral ossification indicate that OI is a biologically complex phenotype going beyond its known impacts on bone to negatively affect linear growth.
Topics: Animals; Mice; Cartilage; Collagen Type I; Gene Expression; Osteogenesis Imperfecta
PubMed: 37796615
DOI: 10.1172/jci.insight.171984