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Critical Reviews in Biotechnology Mar 2022The cultured meat market has been growing at an accelerated space since the first creation of cultured meat burger back in 2013. Substantial efforts have been made to... (Review)
Review
The cultured meat market has been growing at an accelerated space since the first creation of cultured meat burger back in 2013. Substantial efforts have been made to reduce costs by eliminating serum in growth media and improving process efficiency by employing bioreactors. In parallel, efforts are also being made on scaffolding innovations to offer better cells proliferation, differentiation and tissue development. So far, scaffolds used in cultured meat research are predominantly collagen and gelatin, which are animal-derived. To align with cell-based meat vision i.e. environment conservation and animal welfare, plant-derived biomaterials for scaffolding are being intensively explored. This paper reviews and discusses the advantages and disadvantages of scaffold materials and potential scaffolding related to scale-up solution for the production of cultured meat.
Topics: Animals; Biocompatible Materials; Bioreactors; Cell Proliferation; Meat; Tissue Engineering; Tissue Scaffolds
PubMed: 34151657
DOI: 10.1080/07388551.2021.1931803 -
European Journal of Medicinal Chemistry Mar 2023Kirsten rat sarcoma viral (KRAS) oncogene is the most commonly mutated isoform of RAS, accounting for 85% of RAS-driven human cancers. KRAS functioning as a signaling... (Review)
Review
Kirsten rat sarcoma viral (KRAS) oncogene is the most commonly mutated isoform of RAS, accounting for 85% of RAS-driven human cancers. KRAS functioning as a signaling hub participates in multiple cellular signaling pathways and regulates a variety of critical processes such as cell proliferation, differentiation, growth, metabolism and migration. Over the past decades, KRAS oncoprotein has been considered as an "undruggable" target due to its smooth surface and high GTP/GDP affinity. The breakthrough in directly targeting G12C mutated-KRAS and recently approved covalent KRAS inhibitors sotorasib and adagrasib broke the myth of KRAS undruggable and confirmed the directly targeting KRAS as one of the most promising strategies for the treatment of cancers. Targeting KRAS successfully enriched the understanding of KRAS and brought opportunities for the development of inhibitors to directly target other KRAS mutations. With the stage now set for a new era in the treatment of KRAS-driven cancers, the development of KRAS inhibitors also enters a booming epoch. In this review, we overviewed the research progress of KRAS inhibitors with the potential to treat cancers covering articles published in 2022. The design strategies, discovery processes, structure-activity relationship (SAR) studies, cocrystal structure analysis as well as in vitro and in vivo activity were highlighted with the aim of providing updated sight to accelerate the further development of more potent inhibitors targeting various mutated-KRAS with favorable drug-like properties.
Topics: Humans; Kirsten murine sarcoma virus; Proto-Oncogene Proteins p21(ras); Cell Differentiation; Cell Proliferation; Mutation
PubMed: 36680986
DOI: 10.1016/j.ejmech.2023.115124 -
Nature Communications Jun 2020Fusobacterium nucleatum is an oral anaerobe recently found to be prevalent in human colorectal cancer (CRC) where it is associated with poor treatment outcome. In mice,...
Fusobacterium nucleatum is an oral anaerobe recently found to be prevalent in human colorectal cancer (CRC) where it is associated with poor treatment outcome. In mice, hematogenous F. nucleatum can colonize CRC tissue using its lectin Fap2, which attaches to tumor-displayed Gal-GalNAc. Here, we show that Gal-GalNAc levels increase as human breast cancer progresses, and that occurrence of F. nucleatum gDNA in breast cancer samples correlates with high Gal-GalNAc levels. We demonstrate Fap2-dependent binding of the bacterium to breast cancer samples, which is inhibited by GalNAc. Intravascularly inoculated Fap2-expressing F. nucleatum ATCC 23726 specifically colonize mice mammary tumors, whereas Fap2-deficient bacteria are impaired in tumor colonization. Inoculation with F. nucleatum suppresses accumulation of tumor infiltrating T cells and promotes tumor growth and metastatic progression, the latter two of which can be counteracted by antibiotic treatment. Thus, targeting F. nucleatum or Fap2 might be beneficial during treatment of breast cancer.
Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Colony Count, Microbial; DNA, Bacterial; Disease Models, Animal; Disease Progression; Female; Fusobacterium nucleatum; Galactosamine; Galactose; Genome, Bacterial; Humans; Immunity; Lung Neoplasms; Mice, Inbred BALB C; Neoplasm Metastasis
PubMed: 32591509
DOI: 10.1038/s41467-020-16967-2 -
The Lancet. Diabetes & Endocrinology Oct 2022Obesity predominantly affects populations in high-income countries and those countries facing epidemiological transition. The risk of childhood obesity is increased... (Observational Study)
Observational Study
Association between fetal abdominal growth trajectories, maternal metabolite signatures early in pregnancy, and childhood growth and adiposity: prospective observational multinational INTERBIO-21st fetal study.
BACKGROUND
Obesity predominantly affects populations in high-income countries and those countries facing epidemiological transition. The risk of childhood obesity is increased among infants who had overweight or obesity at birth, but in low-resource settings one in five infants are born small for gestational age. We aimed to study the relationships between: (1) maternal metabolite signatures; (2) fetal abdominal growth; and (3) postnatal growth, adiposity, and neurodevelopment.
METHODS
In the prospective, multinational, observational INTERBIO-21st fetal study, conducted in maternity units in Pelotas (Brazil), Nairobi (Kenya), Karachi (Pakistan), Soweto (South Africa), Mae Sot (Thailand), and Oxford (UK), we enrolled women (≥18 years, with a BMI of less than 35 kg/m, natural conception, and a singleton pregnancy) who initiated antenatal care before 14 weeks' gestation. Ultrasound scans were performed every 5±1 weeks until delivery to measure fetal growth and feto-placental blood flow, and we used finite mixture models to derive growth trajectories of abdominal circumference. The infants' health, growth, and development were monitored from birth to age 2 years. Early pregnancy maternal blood and umbilical cord venous blood samples were collected for untargeted metabolomic analysis.
FINDINGS
From Feb 8, 2012, to Nov 30, 2019, we enrolled 3598 pregnant women and followed up their infants to 2 years of age. We identified four ultrasound-derived trajectories of fetal abdominal circumference growth that accelerated or decelerated within a crucial 20-25 week gestational age window: faltering growth, early accelerating growth, late accelerating growth, and median growth tracking. These distinct phenotypes had matching feto-placental blood flow patterns throughout pregnancy, and different growth, adiposity, vision, and neurodevelopment outcomes in early childhood. There were 709 maternal metabolites with positive effect for the faltering growth phenotype and 54 for the early accelerating growth phenotype; 31 maternal metabolites had a negative effect for the faltering growth phenotype and 76 for the early accelerating growth phenotype. Metabolites associated with the faltering growth phenotype had statistically significant odds ratios close to 1·5 (ie, suggesting upregulation of metabolic pathways of impaired fetal growth). The metabolites had a reciprocal relationship with the early accelerating growth phenotype, with statistically significant odds ratios close to 0.6 (ie, suggesting downregulation of fetal growth acceleration). The maternal metabolite signatures included 5-hydroxy-eicosatetraenoic acid, and 11 phosphatidylcholines linked to oxylipin or saturated fatty acid sidechains. The fungicide, chlorothalonil, was highly abundant in the early accelerating growth phenotype group.
INTERPRETATION
Early pregnancy lipid biology associated with fetal abdominal growth trajectories is an indicator of patterns of growth, adiposity, vision, and neurodevelopment up to the age of 2 years. Our findings could contribute to the earlier identification of infants at risk of obesity.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Adiposity; Female; Fetal Development; Fungicides, Industrial; Humans; Kenya; Oxylipins; Pediatric Obesity; Phosphatidylcholines; Placenta; Pregnancy; Prenatal Care; Prospective Studies; South Africa; Ultrasonography, Prenatal
PubMed: 36030799
DOI: 10.1016/S2213-8587(22)00215-7 -
PloS One 2019Skin aging is a complex process, and alterations in human skin due to aging have distinct characteristic as compared to other organs. The aging of dermal cells and the...
Skin aging is a complex process, and alterations in human skin due to aging have distinct characteristic as compared to other organs. The aging of dermal cells and the biological mechanisms involved in this process are key areas to understand skin aging. A large number of biological mechanisms, such as decreasing of protein synthesis of extracellular matrix or increasing of degradation, are known to be altered through skin aging. However, environmental influence can accelerate this characteristic phenotype. In this study, we analyzed primary human dermal fibroblasts in three different in-vitro aging models-UVB irradiation and accelerated proliferation of human dermal fibroblasts from young donors as well as from elderly donors-for the gene expression of COL1A1, COL1A2, COL3A1, COL4A1, COL7A1, MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP12, MMP13, MMP14, TIMP1, TIMP2, TIMP3, TIMP4, IL1B, IL1A, IL6, IL8, IL10, PTGS2, TP53, CASP3, LMNA, SIRT1. We compared the gene expression levels with young control. Furthermore, the behavior of skin fibroblasts was also evaluated using cell growth rate. The findings reveal that the gene expression levels in skin fibroblasts was altered in the process of aging in all three in-vitro aging models, and the cell growth rate was reduced, suggesting that these methods can be employed to understand skin aging mechanisms as well as drug discovery screening method.
Topics: Cell Proliferation; Cells, Cultured; Cellular Senescence; Child; Female; Fibroblasts; Gene Expression; Humans; Male; Middle Aged; Models, Biological; Skin; Skin Aging; Ultraviolet Rays
PubMed: 31269075
DOI: 10.1371/journal.pone.0219165 -
The Cochrane Database of Systematic... Dec 2020The introduction and advancement of enteral feeds for preterm or low birth weight infants is often delayed because of concerns that early full enteral feeding will not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The introduction and advancement of enteral feeds for preterm or low birth weight infants is often delayed because of concerns that early full enteral feeding will not be well tolerated or may increase the risk of necrotising enterocolitis. Early full enteral feeding, however, might increase nutrient intake and growth rates; accelerate intestinal physiological, metabolic, and microbiomic postnatal transition; and reduce the risk of complications associated with intravascular devices for fluid administration. OBJECTIVES: To determine how early full enteral feeding, compared with delayed or progressive introduction of enteral feeds, affects growth and adverse events such as necrotising enterocolitis, in preterm or low birth weight infants.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials; MEDLINE Ovid, Embase Ovid, Maternity & Infant Care Database Ovid, the Cumulative Index to Nursing and Allied Health Literature, and clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials to October 2020.
SELECTION CRITERIA
Randomised controlled trials that compared early full enteral feeding with delayed or progressive introduction of enteral feeds in preterm or low birth weight infants.
DATA COLLECTION AND ANALYSIS
We used the standard methods of Cochrane Neonatal. Two review authors separately assessed trial eligibility, evaluated trial quality, extracted data, and synthesised effect estimates using risk ratios (RR), risk differences, and mean differences (MD) with 95% confidence intervals (CI). We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
We included six trials. All were undertaken in the 2010s in neonatal care facilities in India. In total, 526 infants participated. Most were very preterm infants of birth weight between 1000 g and 1500 g. Trials were of good methodological quality, but a potential source of bias was that parents, clinicians, and investigators were not masked. The trials compared early full feeding (60 mL/kg to 80 mL/kg on day one after birth) with minimal enteral feeding (typically 20 mL/kg on day one) supplemented with intravenous fluids. Feed volumes were advanced daily as tolerated by 20 mL/kg to 30 mL/kg body weight to a target steady-state volume of 150 mL/kg to 180 mL/kg/day. All participating infants were fed preferentially with maternal expressed breast milk, with two trials supplementing insufficient volumes with donor breast milk and four supplementing with preterm formula. Few data were available to assess growth parameters. One trial (64 participants) reported a slower rate of weight gain (median difference -3.0 g/kg/day), and another (180 participants) reported a faster rate of weight gain in the early full enteral feeding group (MD 1.2 g/kg/day). We did not meta-analyse these data (very low-certainty evidence). None of the trials reported rate of head circumference growth. One trial reported that the mean z-score for weight at hospital discharge was higher in the early full enteral feeding group (MD 0.24, 95% CI 0.06 to 0.42; low-certainty evidence). Meta-analyses showed no evidence of an effect on necrotising enterocolitis (RR 0.98, 95% CI 0.38 to 2.54; 6 trials, 522 participants; I² = 51%; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Trials provided insufficient data to determine with any certainty how early full enteral feeding, compared with delayed or progressive introduction of enteral feeds, affects growth in preterm or low birth weight infants. We are uncertain whether early full enteral feeding affects the risk of necrotising enterocolitis because of the risk of bias in the trials (due to lack of masking), inconsistency, and imprecision.
Topics: Body Weight; Enteral Nutrition; Enterocolitis, Necrotizing; Fluid Therapy; Humans; Infant Formula; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Milk, Human; Randomized Controlled Trials as Topic; Weight Gain
PubMed: 33368149
DOI: 10.1002/14651858.CD013542.pub2 -
Circulation May 2024Myocardial infarction (MI) and heart failure are associated with an increased incidence of cancer. However, the mechanism is complex and unclear. Here, we aimed to test...
BACKGROUND
Myocardial infarction (MI) and heart failure are associated with an increased incidence of cancer. However, the mechanism is complex and unclear. Here, we aimed to test our hypothesis that cardiac small extracellular vesicles (sEVs), particularly cardiac mesenchymal stromal cell-derived sEVs (cMSC-sEVs), contribute to the link between post-MI left ventricular dysfunction (LVD) and cancer.
METHODS
We purified and characterized sEVs from post-MI hearts and cultured cMSCs. Then, we analyzed cMSC-EV cargo and proneoplastic effects on several lines of cancer cells, macrophages, and endothelial cells. Next, we modeled heterotopic and orthotopic lung and breast cancer tumors in mice with post-MI LVD. We transferred cMSC-sEVs to assess sEV biodistribution and its effect on tumor growth. Finally, we tested the effects of sEV depletion and spironolactone treatment on cMSC-EV release and tumor growth.
RESULTS
Post-MI hearts, particularly cMSCs, produced more sEVs with proneoplastic cargo than nonfailing hearts did. Proteomic analysis revealed unique protein profiles and higher quantities of tumor-promoting cytokines, proteins, and microRNAs in cMSC-sEVs from post-MI hearts. The proneoplastic effects of cMSC-sEVs varied with different types of cancer, with lung and colon cancers being more affected than melanoma and breast cancer cell lines. Post-MI cMSC-sEVs also activated resting macrophages into proangiogenic and protumorigenic states in vitro. At 28-day follow-up, mice with post-MI LVD developed larger heterotopic and orthotopic lung tumors than did sham-MI mice. Adoptive transfer of cMSC-sEVs from post-MI hearts accelerated the growth of heterotopic and orthotopic lung tumors, and biodistribution analysis revealed accumulating cMSC-sEVs in tumor cells along with accelerated tumor cell proliferation. sEV depletion reduced the tumor-promoting effects of MI, and adoptive transfer of cMSC-sEVs from post-MI hearts partially restored these effects. Finally, spironolactone treatment reduced the number of cMSC-sEVs and suppressed tumor growth during post-MI LVD.
CONCLUSIONS
Cardiac sEVs, specifically cMSC-sEVs from post-MI hearts, carry multiple protumorigenic factors. Uptake of cMSC-sEVs by cancer cells accelerates tumor growth. Treatment with spironolactone significantly reduces accelerated tumor growth after MI. Our results provide new insight into the mechanism connecting post-MI LVD to cancer and propose a translational option to mitigate this deadly association.
Topics: Animals; Extracellular Vesicles; Heart Failure; Myocardial Infarction; Mice; Humans; Female; Lung Neoplasms; Cell Line, Tumor; Mesenchymal Stem Cells; Mice, Inbred C57BL; Disease Models, Animal; Male; Cell Proliferation
PubMed: 38487879
DOI: 10.1161/CIRCULATIONAHA.123.066911 -
Pharmacological Research Sep 2020Spermidine, as a natural component from polyamine members, is originally isolated from semen and also existed in many natural plants, and can be responsible for cell... (Review)
Review
Spermidine, as a natural component from polyamine members, is originally isolated from semen and also existed in many natural plants, and can be responsible for cell growth and development in eukaryotes. The supplementation of spermidine can extend health and lifespan across species. Although the elevated levels of polyamines and the regulation of rate-limiting enzymes for polyamine metabolism have been identified as the biomarkers in many cancers, recent epidemiological data support that an increased uptake of spermidine as a caloric restriction mimic can reduce overall mortality associated with cancers. The possible mechanisms between spermidine and cancer development may be related to the precise regulation of polyamine metabolism, anti-cancer immunosurveillance, autophagy, and apoptosis. Increased intake of polyamine seems to suppress tumorigenesis, but appears to accelerate the growth of established tumors. Based on these observations and the absolute requirement for polyamines in tumor growth, spermidine could be a rational target for chemoprevention and clinical therapeutics of cancers.
Topics: Animals; Antineoplastic Agents; Apoptosis; Autophagy; Biomarkers, Tumor; Cell Proliferation; Humans; Neoplasms; Predictive Value of Tests; Signal Transduction; Spermidine
PubMed: 32461185
DOI: 10.1016/j.phrs.2020.104943 -
The American Journal of Clinical... Jan 2023Little is known regarding the association between weight change and accelerated aging.
BACKGROUND
Little is known regarding the association between weight change and accelerated aging.
OBJECTIVES
This study aimed to estimate the influence of weight change across adulthood on biological aging acceleration in middle-aged and older adults in the United States.
METHODS
We used data of 5553 adults (40-84 y) from the National Health and Nutrition Examination Survey 1999-2010. Weight change patterns (i.e., stable normal, maximal overweight, obese to nonobese, nonobese to obese, and stable obese) and absolute weight change groups across adulthood (i.e., from young to middle adulthood, young to late adulthood, and middle to late adulthood) were defined. A biological aging measure (i.e., phenotypic age acceleration [PhenoAgeAccel]) at late adulthood was calculated. Survey analysis procedures with the survey weights were performed.
RESULTS
Across adulthood, maximal overweight, nonobese to obese, and stable obesity were consistently associated with higher PhenoAgeAccel. For instance, from young to middle adulthood, compared with participants who had stable normal weight, participants experiencing maximal overweight, moving from the nonobese to obese, and maintaining obesity had 1.71 (standard error [SE], 0.21; P < 0.001), 3.62 (SE, 0.28; P < 0.001), and 6.61 (SE, 0.58; P < 0.001) higher PhenoAgeAccel values, respectively. From young to middle adulthood, relative to absolute weight loss or gain of <2.5 kg, weight loss of ≥2.5 kg was marginally associated with lower PhenoAgeAccel (P = 0.054), whereas an obese to nonobese pattern from middle to late adulthood was associated with higher PhenoAgeAccel (P < 0.001).
CONCLUSIONS
Maximal overweight, nonobese to obese, and stable obesity across adulthood, as well as an obese to nonobese pattern from middle to late adulthood, were associated with accelerated biological aging. In contrast, weight loss from young to middle adulthood was associated with decelerated biological aging. The findings highlight the potential role of weight management across adulthood for aging. Monitoring weight fluctuation may help identify the population at high risk of accelerated aging.
Topics: Middle Aged; Humans; United States; Aged; Adult; Overweight; Body Mass Index; Nutrition Surveys; Obesity; Aging; Weight Loss; Risk Factors
PubMed: 36789928
DOI: 10.1016/j.ajcnut.2022.10.020 -
International Journal of Nanomedicine 2023Aptamers are widely applied to diagnosis and therapy because of their targeting. However, the current progress of research into aptamers for the treatment of eye... (Review)
Review
Aptamers are widely applied to diagnosis and therapy because of their targeting. However, the current progress of research into aptamers for the treatment of eye disorders has not been well-documented. The current literature on aptamers was reviewed in this study. Aptamer-related drugs and biochemical sensors have been evaluated for several eye disorders within the past decade; S58 targeting TGF-β receptor II and pegaptanib targeting vascular endothelial growth factor (VEGF) are used to prevent fibrosis after glaucoma filtration surgery. Anti-brain-derived neurotrophic factor aptamer has been used to diagnose glaucoma. The first approved aptamer drug (pegaptanib) has been used to inhibit angiogenesis in age-related macular degeneration (AMD) and diabetic retinopathy (DR), and its efficacy and safety have been demonstrated in clinical trials. Aptamers, including E10030, RBM-007, AS1411, and avacincaptad pegol, targeting other angiogenesis-related biomarkers have also been discovered and subjected to clinical trials. Aptamers, such as C promoter binding factor 1, CD44, and advanced end products in AMD and DR, targeting other signal pathway proteins have also been discovered for therapy, and biochemical sensors for early diagnosis have been developed based on aptamers targeting VEGF, connective tissue growth factor, and lipocalin 1. Aptamers used for early detection and treatment of ocular tumors were derived from other disease biomarkers, such as CD71, nucleolin, and high mobility group A. In this review, the development and application of aptamers in eye disorders in recent years are systematically discussed, which may inspire a new link between aptamers and eye disorders. The aptamer development trajectory also facilitates the discovery of the pathogenesis and therapeutic strategies for various eye disorders.
Topics: Humans; Vascular Endothelial Growth Factor A; Ophthalmology; Macular Degeneration; Aptamers, Nucleotide; Diabetic Retinopathy; Glaucoma; Acceleration
PubMed: 37551274
DOI: 10.2147/IJN.S418115