Anticancer Effect of Hemin through ANO1 Inhibition in Human Prostate Cancer Cells.

Anoctamin1 (ANO1), a calcium-activated chloride channel, is overexpressed in a variety of cancer cells, including prostate cancer, and is involved in cancer cell proliferation, migration, and invasion. Inhibition of ANO1 in these cancer cells exhibits anticancer effects. In this study, we conducted a screening to identify novel ANO1 inhibitors with anticancer effects using PC-3 human prostate carcinoma cells. Screening of 2978 approved and investigational drugs revealed that hemin is a novel ANO1 inhibitor with an IC50 value of 0.45 µM. Notably, hemin had no significant effect on intracellular calcium signaling and cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic AMP (cAMP)-regulated chloride channel, and it showed a weak inhibitory effect on ANO2 at 3 µM, a concentration that completely inhibits ANO1. Interestingly, hemin also significantly decreased ANO1 protein levels and strongly inhibited the cell proliferation and migration of PC-3 cells in an ANO1-dependent manner. Furthermore, it strongly induced caspase-3 activation, PARP degradation, and apoptosis in PC-3 cells. These findings suggest that hemin possesses anticancer properties via ANO1 inhibition and could be considered for development as a novel treatment for prostate cancer.

Fructose malabsorption in ChREBP-deficient mice disrupts the small intestine immune microenvironment and leads to diarrhea-dominant bowel habit changes.

BACKGROUND: The mechanism by which incompletely absorbed fructose causes gastrointestinal symptoms is not fully understood. In this study, we investigated the immunological mechanisms of bowel habit changes associated with fructose malabsorption by examining Chrebp-knockout mice exhibiting defective fructose absorption. METHODS: Mice were fed a high-fructose diet (HFrD), and stool parameters were monitored. The gene expression in the small intestine was analyzed by RNA sequencing. Intestinal immune responses were assessed. The microbiota composition was determined by 16S rRNA profiling. Antibiotics were used to assess the relevance of microbes for HFrD-induced bowel habit changes. RESULTS: Chrebp-knockout (KO) mice fed HFrD showed diarrhea. Small-intestine samples from HFrD-fed Chrebp-KO mice revealed differentially expressed genes involved in the immune pathways, including IgA production. The number of IgA-producing cells in the small intestine decreased in HFrD-fed Chrebp-KO mice. These mice showed signs of increased intestinal permeability. Chrebp-KO mice fed a control diet showed intestinal bacterial imbalance, which the HFrD exaggerated. Bacterial reduction improved diarrhea-associated stool parameters and restored the decreased IgA synthesis induced in HFrD-fed Chrebp-KO mice. CONCLUSIONS: The collective data indicate that gut microbiome imbalance and disrupting homeostatic intestinal immune responses account for the development of gastrointestinal symptoms induced by fructose malabsorption.

Inhibition of ANO1 by Cis- and Trans-Resveratrol and Their Anticancer Activity in Human Prostate Cancer PC-3 Cells.

Anoctamin1 (ANO1), a calcium-activated chloride channel, is involved in the proliferation, migration, and invasion of various cancer cells including head and neck squamous cell carcinoma, lung cancer, and prostate cancer. Inhibition of ANO1 activity or downregulation of ANO1 expression in these cancer cells is known to exhibit anticancer effects. Resveratrol, a natural polyphenol abundant in wines, grapes, berries, soybeans, and peanuts, shows a wide variety of biological effects including anti-inflammatory, antioxidant, and anticancer activities. In this study, we investigated the effects of two stereoisomers of resveratrol on ANO1 activity and found that cis- and trans-resveratrol inhibited ANO1 activity with different potencies. Cis- and trans-resveratrol inhibited ANO1 channel activity with IC50 values of 10.6 and 102 µM, respectively, and had no significant effect on intracellular calcium signaling at 10 and 100 µM, respectively. In addition, cis-resveratrol downregulated mRNA and protein expression levels of ANO1 more potently than trans-resveratrol in PC-3 prostate cancer cells. Cis- and trans-resveratrol significantly reduced cell proliferation and cell migration in an ANO1-dependent manner, and both resveratrol isomers strongly increased caspase-3 activity, PARP cleavage, and apoptotic sub-G1 phase ratio in PC-3 cells. These results revealed that cis-resveratrol is a potent inhibitor of ANO1 and exhibits ANO1-dependent anticancer activity against human metastatic prostate cancer PC-3 cells.

Ability of soluble ST2 to predict left ventricular remodeling in patients with acute coronary syndrome.

The association of the soluble suppression of tumorigenicity 2 (sST2) and the prognosis of heart failure have been well evaluated. However, little is known about the prediction of sST2 for left ventricular (LV) remodeling in acute coronary syndrome (ACS). We investigated the ability of sST2 to predict LV remodeling following the revascularization of ACS. From May 2019 to December 2020, 95 patients with LV ejection fraction (EF) < 50% who underwent coronary revascularization for ACS (unstable angina, non-ST-elevation myocardial infarction, ST-elevation myocardial infarction) were enrolled. Echocardiography and sST2 were performed at baseline and at a 3-month follow-up. The association between LV remodeling, using the end-diastolic volume index, and sST2 at baseline and at the 3-month follow-up, and the difference between each value was explored. During follow-up, 41 patients showed LV adverse remodeling. The baseline sST2 increased in patients without adverse remodeling (32.05 ng/mL vs. 23.5 ng/mL, p < 0.001), although clinical characteristics were similar between the two groups. During the mean follow-up of 3 months, a significant correlation was found in the changes between sST2 and LV end-diastolic/systolic volume index (r = 0.649; p < 0.001, r = 0.618; p < 0.001, respectively), but not in the changes of LVEF (r = - 0.132, p = 0.204). The use of angiotensin-converting enzyme 2 inhibitors/receptor blockers was higher (90.7% vs. 53.7%, p < 0.001) and sST2 decreased more predominantly in patients without adverse remodeling (23.18 ng/mL vs 26.40 ng/mL, p = 0.003). However, the changes in sST2 and LV volume were not different according to the ACS types (p > 0.05, for all). Estimates of the odds ratio (OR) for remodeling according to the sST2 difference increased substantially with a negative increase in the sST2 difference. Multivariable analysis found that, the difference between the baseline and 3-month sST2 was the most important determinant of LV remodeling following the revascularization of ACS (OR 1.24; 95% confidence interval: 1.09 to 1.41; p = 0.001). In conclusion, an increase in sST2 during follow-up was a useful predictor of LV remodeling.

Generation of zinc ion-rich surface via in situ growth of ZIF-8 particle: Microorganism immobilization onto fabric surface for prohibit hospital-acquired infection.

Viruses/bacteria outbreaks have motivated us to develop a fabric that will inhibit their transmission with high potency and long-term stability. By creating a metal-ion-rich surface onto polyester (PET) fabric, a method is found to inhibit hospital-acquired infections by immobilizing microorganisms on its surface. ZIF-8 and APTES are utilized to overcome the limitations associated with non-uniform distribution, weak biomolecule interaction, and ion leaching on surfaces. Modified surfaces employing APTES enhance ZIF-8 nucleation by generating a monolayer of self-assembled amine molecules. An in-situ growth approach is then used to produce evenly distributed ZIF-8 throughout it. In comparison with pristine fabric, this large amount of zinc obtained from the modification of the fabric has a higher affinity for interacting with membranes of microorganisms, leading to a 4.55-fold increase in coronavirus spike-glycoprotein immobilization. A series of binding ability stability tests on the surface demonstrate high efficiency of immobilization, >90%, of viruses and model proteins. The immobilization capacity of the modification fabric stayed unchanged after durability testing, demonstrating its durability and stability. It has also been found that this fabric surface modification approach has maintained air/vapor transmittance and air permeability levels comparable to pristine fabrics. These results strongly advocate this developed fabric has the potential for use as an outer layer of face masks or as a medical gown to prevent hospital-acquired infections.

Effect of Phlorofucofuroeckol A and Dieckol Extracted from Ecklonia cava on Noise-induced Hearing Loss in a Mouse Model.

One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.

Co-existing "spear-and-shield" air filter: Anchoring proteinaceous pathogen and self-sterilized nanocoating for combating viral pandemic.

Infectious pollutants bioaerosols can threaten human public health. In particular, the indoor environment provides a unique exposure situation to induce infection through airborne transmission like SARS-CoV-2. To prevent the infection from spreading, personal protective equipment or indoor air purification is necessary. However, it has been discovered that the conventional filter can become contaminated by pathogen-containing aerosols, meaning that advanced filtering and self-sterilization systems are required. Here, we fabricate a multilayered nanocoating around the fabric using laponite (LAP) with Cu2+ ions (LAP-Cu2+ nanocoating) two contradictory functions in one system: trapping proteinaceous pathogens and antibacterial effect. Due to the strong LAP-protein interaction, albumin and spike protein (S-protein) are trapped into the fabric when proteins are sprayed using a nebulizer. The protein-blocking performance of the nanocoated fabric is 9.55-fold higher than bare fabric. These trapping capacities are retained after rinsing and repeated adsorption cycles, showing reproducibility for air filtration. Even though the protein-binding occurred, the LAP-Cu2+ fabric indicates antibacterial effect. LAP-Cu2+ fabric has an equivalent air and water transmittance rate to that of bare fabric with a stability under physiological environment. Therefore, given its excellent "Spear-and-shield" functions, the proposed LAP-Cu2+ fabric shows great potential for use in filter and masks during the viral pandemic.

Domino [4 + 2] Annulation Access to Quinone-Indolizine Hybrids: Anticancer N-Fused Polycycles.

A highly efficient synthetic route to new quinone-indolizine hybrids was accomplished from quinones and N-substituted pyrrole-2-carboxaldehydes via a domino Michael addition-aldol condensation-aromatization sequence through which the central pyridine ring was constructed in atom-economical and environment-friendly manner. Post modification of the resulting products was also demonstrated, enabling further expansion of this heterocyclic chemical space. Biological evaluation of the quinone-indolizine hybrids revealed potent anticancer effects in human prostate adenocarcinoma cells (PC-3) and oral adenosquamous carcinoma cells (CAL-27).

Diversity-oriented generation and biological evaluation of new chemical scaffolds bearing a 2,2-dimethyl-2H-chromene unit: Discovery of novel potent ANO1 inhibitors.

Chemical territory bearing a 2,2-dimethyl-2H-chromene motif was expanded by utilizing an o-hydroxy aldehyde group of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde as a synthetic handle to install distinctive morphology and functionality of each scaffold. Cell based assays and in silico docking analysis led us to discover that these new compounds exhibit inhibitory effect on anoctamin1 (ANO1). ANO1 is amplified and highly expressed in various carcinomas including prostate cancer, esophageal cancer, breast cancer, and pancreatic cancer. Biological assays revealed that (E)-1-(7,7-dimethyl-7H-furo[2,3-f]chromen-2-yl)-3-(1H-pyrrol-2-yl)prop-2-en-1-one (3n, Ani-FCC) is a novel, potent and selective ANO1 inhibitor with an IC50 value of 1.23 µM. 3n showed 144 times stronger activity on ANO1 inhibition than ANO2 inhibition and did not alter the chloride channel activity of CFTR and the intracellular calcium signaling. Notably, 3n strongly decreased cell viability of PC-3 and FaDu cells expressing high levels of ANO1 with a decrease in ANO1 protein levels. In addition, 3n significantly enhanced apoptosis via activation of caspase 3 and cleavage of PARP in PC-3 and FaDu cells. This study shows that a novel ANO1 inhibitor, 3n, can be a potential candidate for the treatment of cancers overexpressing ANO1, such as prostate cancer and esophageal cancer.

Changes in microRNA Expression in the Cochlear Nucleus and Inferior Colliculus after Acute Noise-Induced Hearing Loss.

Noise-induced hearing loss (NIHL) can lead to secondary changes that induce neural plasticity in the central auditory pathway. These changes include decreases in the number of synapses, the degeneration of auditory nerve fibers, and reorganization of the cochlear nucleus (CN) and inferior colliculus (IC) in the brain. This study investigated the role of microRNAs (miRNAs) in the neural plasticity of the central auditory pathway after acute NIHL. Male Sprague-Dawley rats were exposed to white band noise at 115 dB for 2 h, and the auditory brainstem response (ABR) and morphology of the organ of Corti were evaluated on days 1 and 3. Following noise exposure, the ABR threshold shift was significantly smaller in the day 3 group, while wave II amplitudes were significantly larger in the day 3 group compared to the day 1 group. The organ of Corti on the basal turn showed evidence of damage and the number of surviving outer hair cells was significantly lower in the basal and middle turn areas of the hearing loss groups relative to controls. Five and three candidate miRNAs for each CN and IC were selected based on microarray analysis and quantitative reverse transcription PCR (RT-qPCR). The data confirmed that even short-term acoustic stimulation can lead to changes in neuroplasticity. Further studies are needed to validate the role of these candidate miRNAs. Such miRNAs may be used in the early diagnosis and treatment of neural plasticity of the central auditory pathway after acute NIHL.

Punicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2.

Lupus nephritis (LN) is the most frequent phenotype in patients with systemic lupus erythematosus (SLE) and has a high rate of progression to end-stage renal disease, in spite of intensive treatment and maintenance therapies. Recent evidence suggests that protease-activated receptor-2 (PAR2) is a therapeutic target for glomerulonephritis. In this study, we performed a cell-based high-throughput screening and identified a novel potent PAR2 antagonist, punicalagin (PCG, a major polyphenol enriched in pomegranate), and evaluated the effects of PCG on LN. The effect of PCG on PAR2 inhibition was observed in the human podocyte cell line and its effect on LN was evaluated in NZB/W F1 mice. In the human podocyte cell line, PCG potently inhibited PAR2 (IC50 = 1.5 ± 0.03 µM) and significantly reduced the PAR2-mediated activation of ERK1/2 and NF-κB signaling pathway. In addition, PCG significantly decreased PAR2-induced increases in ICAM-1 and VCAM-1 as well as in IL-8, IFN-γ, and TNF-α expression. Notably, the intraperitoneal administration of PCG significantly alleviated kidney injury and splenomegaly and reduced proteinuria and renal ICAM-1 and VCAM-1 expression in NZB/W F1 mice. Our results suggest that PCG has beneficial effects on LN via inhibition of PAR2, and PCG is a potential therapeutic agent for LN.

Novel ANO1 Inhibitor from Mallotus apelta Extract Exerts Anticancer Activity through Downregulation of ANO1.

Anoctamin1 (ANO1), a calcium-activated chloride channel, is frequently overexpressed in several cancers, including human prostate cancer and oral squamous cell carcinomas. ANO1 plays a critical role in tumor growth and maintenance of these cancers. In this study, we have isolated two new compounds (1 and 2) and four known compounds (3-6) from Mallotus apelta. These compounds were evaluated for their inhibitory effects on ANO1 channel activity and their cytotoxic effects on PC-3 prostate cancer cells. Interestingly, compounds 1 and 2 significantly reduced both ANO1 channel activity and cell viability. Electrophysiological study revealed that compound 2 (Ani-D2) is a potent and selective ANO1 inhibitor, with an IC50 value of 2.64 µM. Ani-D2 had minimal effect on cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity and intracellular calcium signaling. Notably, Ani-D2 significantly reduced ANO1 protein expression levels and cell viability in an ANO1-dependent manner in PC-3 and oral squamous cell carcinoma CAL-27 cells. In addition, Ani-D2 strongly reduced cell migration and induced activation of caspase-3 and cleavage of PARP in PC-3 and CAL-27 cells. This study revealed that a novel ANO1 inhibitor, Ani-D2, has therapeutic potential for the treatment of several cancers that overexpress ANO1, such as prostate cancer and oral squamous cell carcinoma.

Feasibility of dosimetric measurements using Al2O3:C OSL dosimeter during fluoroscopy-guided procedures.

This study investigated the feasibility of dosimetric measurements using Al2O3:C optically stimulated luminescence (OSL) dosimeters during fluoroscopy-guided procedures. The linearity and energy dependence of Al2O3:C OSL dosimeters were evaluated, and the air kerma rate at the operator's position was measured. The response of Al2O3:C OSL dosimeters to short, repetitive irradiations was compared to that of long uninterrupted irradiation. The change in response of the Al2O3:C OSL dosimeter under automatic exposure rate control (AERC) was evaluated with the use of various thicknesses of polymethyl-methacrylate (PMMA) plates (15-30 cm). The Al2O3:C OSL dosimeters could detect 5µGy and showed good linearity in doses of ≥10µGy (R2: 0.997-0.999,p< 0.001). The relative response of the Al2O3:C OSL dosimeter normalised to that of 36.8 keV was 0.828-1.101 at the energies investigated (30.6-46.0 keV). The air kerma rate at the operator's position was estimated to be 2.61-7.17µGy min-1depending on the heights representing different body parts. Repetitive short irradiations had no significant impact on the relative response of the Al2O3:C OSL dosimeters (p> 0.05). Despite a high energy dependence on the low energy beam used in fluoroscopy, the change in relative response of the Al2O3:C OSL dosimeter under AERC was within 5.7% depending on the thickness of the PMMA plates. Dosimetric measurement using Al2O3:C OSL dosimeters for patients and operators is feasible. However, one should be cautious about high standard deviations when measuring small doses of ≤20µGy using Al2O3:C OSL dosimeters. It is essential to perform intensive bleaching before measuring very small doses to minimise pre-irradiation counts.

Protective Functions of Group 3 Late Embryogenesis Abundant (G3LEA) Proteins in Enterococcus faecium During Vancomycin Treatment.

Late embryogenesis abundant (LEA) proteins protect organisms from various environmental stresses; however, the underlying mechanism of LEA mediated therapeutic evasion is still unclear in both eukaryotes and prokaryotes. In this study, group 3 LEA protein (G3LEA) of vancomycin-resistant Enterococcus faecium under sublethal concentration of vancomycin stress was evaluated and shown to have two functions: the first is the reduction of reactive oxygen species (ROS) content, preventing apoptosis by suppressing apoptotic proteins Cas3 and MAOB, and the second is activating specific drug efflux pumps. Sublethal vancomycin model was established with using Propidium Iodide (PI) stain. Real-time PCR was conducted to evaluate the expression of G3lea. Flow cytometry and confocal microscope using Anti- G3LEA, anti- MAOB, and anti- Cas3 were performed to assess the expression of G3LEA. Under sublethal vancomycin stress, G3LEA is upregulated, suppressing the expression of apoptotic markers and increasing specific efflux markers. These results suggest that G3LEA protein suppresses antibiotic mediated apoptosis in prokaryotic cells and plays a key role in understanding and preventing antibiotic resistance.

Drug Loading and Release Behavior Depending on the Induced Porosity of Chitosan/Cellulose Multilayer Nanofilms.

The ability to control drug loading and release is the most important feature in the development of medical devices. In this research, we prepared a functional nanocoating technology to incorporate a drug-release layer onto a desired substrate. The multilayer films were prepared using chitosan (CHI) and carboxymethyl cellulose (CMC) polysaccharides by the layer-by-layer (LbL) method. By using chemical cross-linking to change the inner structure of the assembled multilayer, we could control the extent of drug loading and release. The cross-linked multilayer film had a porous structure and enhanced water wettability. Interestingly, more of the small-molecule drug was loaded into and released from the non-cross-linked multilayer film, whereas more of the macromolecular drug was loaded into and released from the cross-linked multilayer film. These results indicate that drug loading and release can be easily controlled according to the molecular weight of the desired drug by changing the structure of the film.

Development of an Educational Brochure about Treatment Options for Pregnant Women with Opioid Use Disorders.

The goal of this study was to describe the development of an educational brochure for pregnant women with opioid use disorders (OUDs) about treatment options. Based on findings from a preliminary review of the literature, we drafted a brochure that addressed the following questions: (1) What are your options (Medication-Assisted Treatment (MAT) versus no treatment)? (2) What are the benefits of MAT? (3) What are the risks of MAT? (4) Can I take buprenorphine or methadone while breastfeeding? (5) Which medication should I choose? Clinicians and doulas (n = 19) who provide care to pregnant women with OUDs were recruited. Semi-structured interviews elicited participants' feedback on brochure content and their perceptions about brochure use for patient education. Thematic data analyses were performed. Three emergent themes were identified (suggested uses and settings of use, content revisions, and perceptions about the brochure) and used to refine the final brochure. This study provides valuable insights into the desired content of an educational brochure describing treatment options for pregnant women with OUDs from the provider's standpoint. Research is needed to assess the use of the brochure in shared decision-making conversations with providers about treatment.

Effect of diesel exhaust particles on RANK/RANKL expression in in vivo and in vitro models of middle ear inflammation.

OBJECTIVE: Increasing evidence suggests a link between middle ear inflammation and the development of diesel exhaust particles (DEPs). Chronic middle ear inflammation can lead to bone damage and remodeling. This study aimed to explore the impact of DEPs on the expression of interleukin (IL)-6 and RANKL under conditions of middle ear inflammation. METHODS: DEPs were collected by burning fuel in a diesel engine at the Gwangju Institute of Science and Technology. Human middle ear epithelial cells were cultured to 70-80% confluence in culture plates and then treated with DEPs at concentrations of 0, 5, 10, 20, 40, and 80 µg/mL for 24 h. Cell viability was assessed manually. B6.SJL mice, aged 9 weeks, were exposed to DEPs at a concentration of 200 µg/m3 for 1 h daily over a period of 28 days. The expression levels of IL-6, tumor necrosis factor α, RANKL, and RANK were evaluated using hematoxylin and eosin staining and western blot analysis of the harvested middle ear samples. RESULTS: The viability of human middle ear epithelial cells was found to decrease in a dose-dependent manner after 24 h. The mRNA expression level of IL-6 exhibited the most significant increase at the 48-h mark. In contrast, the mRNA expression levels of RANKL and RANK showed a marked increase as early as 6 h post-exposure, with both genes subsequently displaying a time-dependent decrease. Histological analysis revealed that the middle ear mucosa was thicker in the group exposed to DEPs compared to the control group. Additionally, the protein expression levels of IL-6 and RANKL were elevated in the DEP-exposed group relative to the normal control group. CONCLUSIONS: We confirmed the expression of osteoclast-related proteins in the mouse middle ear. These results imply that air pollutants might affect RANKL/RANK signaling, which is associated with bone remodeling.

Anticancer Evaluation of Novel Benzofuran-Indole Hybrids as Epidermal Growth Factor Receptor Inhibitors against Non-Small-Cell Lung Cancer Cells.

The epidermal growth factor receptor (EGFR), also known as ErbB1 and HER1, belongs to the receptor tyrosine kinase family. EGFR serves as the primary driver in non-small-cell lung cancer (NSCLC) and is a promising therapeutic target for NSCLC. In this study, we synthesized a novel chemical library based on a benzofuran-indole hybrid scaffold and identified 8aa as a potent and selective EGFR inhibitor. Interestingly, 8aa not only showed selective anticancer effects against NSCLC cell lines, PC9, and A549, but it also showed significant inhibitory effects against the double mutant L858R/T790M EGFR, which frequently occurs in NSCLC. In addition, in PC9 and A549 cells, 8aa potently blocked the EGFR signaling pathway, cell viability, and cell migration. These findings suggest that 8aa, a benzofuran-indole hybrid derivative, is a novel EGFR inhibitor that may be a potential candidate for the treatment of NSCLC patients with EGFR mutations.

Cultured meat with enriched organoleptic properties by regulating cell differentiation.

Research on cultured meat has primarily focused on the mass proliferation or differentiation of muscle cells; thus, the food characteristics of cultured meat remain relatively underexplored. As the quality of meat is determined by its organoleptic properties, cultured meat with similar sensory characteristics to animal-derived meat is highly desirable. In this study, we control the organoleptic and nutritional properties of cultured meat by tailoring the 2D differentiation of primary bovine myoblasts and primary bovine adipose-derived mesenchymal stem cells on gelatin/alginate scaffolds with varying stiffness. We assess the effect of muscle and adipose differentiation quality on the sensory properties of cultured meat. Thereafter, we fabricate cultured meat with similar sensory profiles to that of conventional beef by assembling the muscle and adipose constructs composed of highly differentiated cells. We introduce a strategy to produce cultured meat with enriched food characteristics by regulating cell differentiation with scaffold engineering.