Aerobic Exercise Improves Radiation Therapy Efficacy in Non-Small Cell Lung Cancer: Preclinical Study Using a Xenograft Mouse Model.

The "oxygen effect" improves radiation efficacy; thus, tumor cell oxygen concentration is a crucial factor for improving lung cancer treatment. In the current study, we aimed to identify aerobic exercise-induced changes in oxygen concentrations in non-small cell lung cancer (NSCLC) cells. To this end, an NSCLC xenograft mouse model was established using human A549 cells. Animals were subsequently subjected to aerobic exercise and radiation three times per week for 2 weeks. Aerobic exercise was performed at a speed of 8.0 m/m for 30 min, and the tumor was irradiated with 2 Gy of 6 MV X-rays (total radiation dose 12 Gy). Combined aerobic exercise and radiation reduced NSCLC cell growth. In addition, the positive effect of aerobic exercise on radiation efficacy through oxygenation of tumor cells was confirmed based on hypoxia-inducible factor-1 and carbonic anhydrase IX expression. Finally, whole-transcriptome analysis revealed the key factors that induce oxygenation in NSCLC cells when aerobic exercise was combined with radiation. Taken together, these results indicate that aerobic exercise improves the effectiveness of radiation in the treatment of NSCLC. This preclinical study provides a basis for the clinical application of aerobic exercise to patients with NSCLC undergoing radiation therapy.

Adolescents diagnosed with polycystic ovary syndrome under the Rotterdam criteria but not meeting the diagnosis under the updated guideline.

STUDY QUESTION: What are the characteristics of adolescents diagnosed with polycystic ovary syndrome (PCOS) based on the 2003 Rotterdam criteria, but who do not meet the diagnosis according to the international evidence-based guideline? SUMMARY ANSWER: Adolescents who had features of PCOS but did not meet the evidence-based guideline adolescent criteria exhibited unfavorable metabolic profiles compared to controls and shared considerable metabolic and hormonal features with adolescents who did meet the adolescent criteria. WHAT IS KNOWN ALREADY: The international evidence-based PCOS guideline recommended that ultrasound should not be used for the diagnosis of PCOS in girls with a gynecological age of <8 years. Thus far, few studies have evaluated the clinical characteristics of the girls diagnosed with PCOS based on the Rotterdam criteria but who do not meet the diagnosis according to the updated guideline. STUDY DESIGN, SIZE, DURATION: This is a retrospective study, and subjects attended for care from 2004 to 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Adolescent girls with PCOS diagnosed according to the 2003 Rotterdam criteria and healthy controls. All participants were between 2 and 8 years since menarche. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 315 girls diagnosed with PCOS according to the Rotterdam criteria, those with irregular menstruation (IM)/hyperandrogenism (HA)/polycystic ovary (PCO), IM/HA, HA/PCO, and IM/PCO phenotypes accounted for 206 (65.4%), 30 (9.5%), 12 (3.8%), and 67 (21.3%) participants, respectively. According to the evidence-based guideline, 79 girls (25.1%) with the HA/PCO or IM/PCO phenotypes were not diagnosed with PCOS, and aligned to the international guideline; they were designated as the 'at-risk' group. As expected, the girls meeting the evidence-based guideline adolescent criteria showed the worst metabolic profiles (degree of generalized or central obesity, frequency of insulin resistance, prediabetes or diabetes, and metabolic syndrome) and higher hirsutism scores than the at-risk group or controls. Approximately 90% of the at-risk group were not overweight or obese, which was similar to the controls. However, they showed worse metabolic profiles, with higher blood pressure, triglyceride, and insulin resistance parameters than controls; furthermore, these profiles were similar to those of the girls meeting the adolescent criteria. The at-risk group showed similarly elevated serum LH levels and LH/FSH ratio with the girls meeting adolescent criteria. LIMITATIONS, REASONS FOR CAUTION: We could not evaluate hormonal or ultrasound parameters in controls. WIDER IMPLICATIONS OF THE FINDINGS: Compared to the conventional Rotterdam criteria, the recent international evidence-based guideline-avoiding ultrasound in PCOS diagnosis in adolescents-still gives the opportunity to identify young girls at risk, aligned to the findings in this study. A practical approach to this adolescent population would involve establishing IM or HA (with ultrasound not indicated) and designating 'at-risk' PCOS status with regular check-ups for newly developed or worsening PCOS-related symptoms or metabolic abnormalities, with subsequent reassessment including ultrasound or anti-Müllerian hormone, once 8 years post-menarche. STUDY FUNDING/COMPETING INTEREST(S): No funding was received in support of this study. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.

Diagnostic utility, disease activity, and disease phenotype correlation of serum ASCA, pANCA, and PR3-ANCA in pediatric inflammatory bowel disease.

OBJECTIVE: This study aimed to evaluate the diagnostic utility, disease activity, and phenotypic association of serum anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), PR3-ANCA, and MPO-ANCA in pediatric patients with inflammatory bowel disease (IBD). METHODS: Pediatric patients diagnosed with IBD were recruited and classified as Crohn's disease (CD), ulcerative colitis (UC), and IBD-unclassified (IBD-U) through full investigation. The Paris classification was used to evaluate disease phenotypes of pediatric CD and UC. RESULTS: In all, 229 pediatric patients with IBD (CD 147, UC 53, IBD-U 29) were included. The ASCA IgG seropositivity significantly differed among the three groups (CD 75.4%, UC 17.5%, and IBD-U 60.0%; p < 0.001). PR3-ANCA positive rates were the highest in UC (24.0%), followed by IBD-U (17.6%), and none in CD (p = 0.002); pANCA-positive rates were higher in IBD-U (33.6%), followed by UC (28.0%) than in CD (1.4%) (p < 0.001). Regarding disease phenotype, perianal disease revealed higher serum ASCA IgG titers (median 36.7 U/mL in P1 vs. 25.2 U/mL in P0, p = 0.019). Serum ASCA IgG and IgA cutoff values to distinguish CD were 32.7 (U/mL) and 11.9 (U/mL), respectively, with a specificity of 80.0%. CONCLUSION: Serological biomarkers of ASCA IgG and IgA were effective for differentiating CD in pediatric IBD patients, and serum pANCA and PR3-ANCA, but not MPO-ANCA, were effective in distinguishing UC and IBD-U. Furthermore, measuring serological titers of ASCA IgG and IgA may help differentiate CD and evaluate the disease activity and phenotype of pediatric IBD in practice.

Greater numbers and sizes of muscle bundles in the breast and leg muscles of broilers compared to layer chickens.

Meat-type (broiler) and egg-type (layer) chickens were bred by intensive selection over the years, resulting in more numbers and larger sizes of myofibers. Although the characteristics are important parameters in muscle growth and meat quality, muscle bundle characteristics have not been studied in poultry. Therefore, this study aimed to compare the histological characteristics of myofibers and muscle bundles in muscles between male broiler (Ross broiler breed) chickens and layer (Hy-Line) chickens. Chicken muscles, pectoralis major (PM) and gastrocnemius (GM), were sampled at the age of 49 days and stained to analyze histological characteristics. Expectedly, body weights (BWs) and weights of PM and GM muscles in 49-day-old broilers were significantly heavier than those in layers. Within PM, broilers exhibited greater number and cross-sectional area (CSA) of myofibers than layers (3.3- and 3.3-fold, respectively). The total number and CSA of PM muscle bundles were approximately 1.5 and 6.6 times greater, respectively, in broilers than layers. Moreover, broilers exhibited 2 times greater number of myofibers per bundle of PM muscle than layers. Within GM, myofiber number and CSA were 2.3- and 2.4-fold greater, respectively, in broilers than layers. In addition, the total number of muscle bundles and bundle CSA were 2.5- and 2.1-fold greater, respectively, in broilers than in the layers. The novel findings of the current study provide evidence that greater muscle mass of broilers occurs by both hyperplasia and hypertrophy of muscle bundles and myofibers.

The Asian Society of Endometriosis and Adenomyosis guidelines for managing adenomyosis.

This is the first guidelines for adenomyosis from the Asian Society of Endometriosis and Adenomyosis.

Effects of apoptotic factor levels on palatability variation during postmortem aging of Holstein longissimus thoracis muscles classified as Warner-Bratzler shear force change value.

This study compared the caspase levels and myofibrillar protein degradation of longissimus thoracis muscles between the two groups with varying extents of tenderization during postmortem aging to investigate the cause of tenderness variation between aged beef from Holstein-Friesian steers. The change value (CV) of Warner-Bratzler shear force (WBS) was determined as the difference in WBS between 0 and 14 d of aging. The higher change (HC) value group exhibited lower WBS and higher initial tenderness values than the lower change (LC) value group aged 14 and 28 d (P < 0.05), even though there was no difference between the CV groups aged 0 d (P > 0.05). The higher tenderness improvement in the HC group at 14 d might be related to the lower cytochrome C and caspase values and higher degradation of desmin and troponin T compared to the LC group (P < 0.05).

Effects of a myostatin mutation in Japanese quail (Coturnix japonica) on the physicochemical and histochemical characteristics of the pectoralis major muscle.

The aim of this study was to compare the carcass, meat quality, and histochemical characteristics of pectoralis major (PM) muscle between wild type (WT) and myostatin (Mstn) homozygous mutant (HO) quail lines. The HO quail line exhibited significantly heavier body weight (HO vs. WT, 115.7 g vs. 106.2 g, approximately 110%) and PM muscle weight (HO vs. WT, 18.0 g vs. 15.2 g, approximately 120%) compared to the WT (p < 0.001). However, the two groups had similar traits (pH, redness, yellowness, and drip loss) for meat quality, although slightly higher lightness and cooking loss were observed in the mutant quail (103% and 141%, respectively, p < 0.05). For histochemical traits of PM muscle, Mstn mutant quail exhibited lower type IIA and higher type IIB percentage in the deep region than WT quail (p < 0.05), indicating a fiber conversion from the type IIA to IIB. However, the two quail lines had comparable histochemical traits in the superficial region (p > 0.05). These data suggest that Mstn mutation greatly increases muscle mass without significantly affecting meat quality.

The Effectiveness and Safety of Methotrexate as the First-Line Immunomodulator of Maintenance Therapy in Pediatric Crohn Disease.

OBJECTIVES: Methotrexate (MTX) has been used as maintenance therapy for Crohn disease (CD) in adults and children. However, there are only a few studies on the MTX's effectiveness in thiopurine-naïve CD adult patients and children. This study aimed to evaluate the MTX's effectiveness and safety as first immunomodulator for maintenance therapy in pediatric CD. METHODS: This retrospective cohort study recruited 64 pediatric CD patients treated with MTX as a first-line immunomodulator. Clinical remission (CR) was assessed at weeks 14, 26, and 52. Mucosal healing (MH) was assessed at weeks 26 and 52. RESULTS: Of 64 patients who received MTX, CR was noted in 60.9% at week 14, 29.7% with MH in 68.0% at week 26, and 27.8% with MH in 81.8% at week 52. When comparing age subtypes according to the Paris classification, the CR rate was higher in A1a than in the other subtypes at week 26 (60.0% in A1a, 26.5% in A1b, 0% in A2; P = 0.038). There were no differences in disease location, behavior, or perianal involvement. Adverse effects were noted in 30 of 64 (46.9%) patients, including 1 patient who stopped MTX before 26 weeks owing to side effects; increased liver enzymes in 25 (39.0%) patients, leukopenia in 5 (7.8%), nausea in 5 (7.8%), skin erosion in 1 (1.6%), and headache in 1 (1.6%). CONCLUSION: MTX as a first-line immunomodulator may be an effective and safe maintenance therapy for pediatric CD patients.

Standardized ileal digestible lysine requirements based on growth performance and histochemical characteristics of male broilers from 10 to 21 d of age.

The growth performance and histochemical characteristics of breast muscle fibers were used to estimate the standardized ileal digestible (SID) Lys requirements for 10- to 21-d-old male broilers. Three hundred and sixty 10-d-old Ross 308 broilers (290 ± 16.6 g) were allocated to 6 diets in a randomized complete block design with 6 replicate cages per treatment and 10 birds per cage. The 6 experimental diets were formulated to contain equally spaced increasing levels of SID Lys from 0.86% to 1.36%. The data were analyzed using the MIXED procedure of SAS. The Lys requirements were estimated by the NLIN procedure of SAS. An increase in dietary SID Lys from 0.86% to 1.36% resulted in a quadratic increase (P < 0.05) in body weight gain (BWG), gain to feed ratio (G:F), breast weight, muscle cross-sectional area (MCSA), and fiber area. The SID Lys requirements based on the one-slope broken-line, quadratic line, the first intercept between the plateau of the one-slope broken-line and quadratic-line models and 95% of the upper asymptote of the quadratic-line model were estimated to be 1.01%, 1.19%, 1.08%, and 1.13% for BWG, 1.06%, 1.22%, 1.11%, and 1.16% for G:F, 1.10%, 1.29%, 1.19%, and 1.22% for breast weight, 1.06%, 1.22%, 1.12%, and 1.16% for MCSA, and 1.14%, 1.22%, 1.16%, and 1.16% for breast muscle fiber area, respectively. It was concluded that the SID Lys requirements for broilers at the age of 10 to 21 d depended on the response variables used for estimation, and that histochemical characteristics of breast muscle fibers could be good indicators for estimating SID Lys requirements.

Research Note: Expression levels of collagen-related genes in PSE conditions and white striping features of broiler pectoralis major muscle.

The objective of this study was to compare the meat quality characteristics and collagen-related gene expression levels in the broiler pectoralis major (PM) muscle among the meat quality groups, including normal, pale, soft, and exudative (PSE), and white striping (WS) groups. The group was classified by their WS degree (moderate or severe striping) and quality traits including pH and lightness values at 24 h postmortem (normal group: pH24 h ≥5.7, 48≤L*≤53, without WS features; PSE group: pH24 h <5.7, L* >53, without WS features; WS group: pH24 h ≥5.7, 48≤L*≤53, with moderate or severe striping). The WS group revealed no differences in all measured meat quality traits compared to the normal group (P > 0.05). PM muscles exhibiting PSE conditions without WS indicated lower pH15 min and pH24 h values (P < 0.05). Whereas, lower lightness and cooking loss values were observed in the normal and WS groups compared to the PSE group (P < 0.05). No significant difference was observed in the level of type I collagen among the groups (P > 0.05), whereas a higher type III collagen level was observed in the WS group than in the other groups (P < 0.05). Additionally, the WS group showed a higher type IV collagen level compared to the normal group (P < 0.05) and a level not different from that of the PSE group (P > 0.05). In contrast, the expression levels of matrix metalloproteinase (MMP) 2, involved in type IV collagen degradation, and angiopoietin-like protein 7, associated with collagen accumulation, were higher in the WS group compared to the normal group (P < 0.05). However, no difference was detected in the MMP1 level among the all groups (P > 0.05). These results suggest that the occurrence of WS features in broiler PM muscle, unlike PSE and normal conditions, can be influenced by the expression levels of collagen-related genes associated with abnormalities in extracellular matrix components.

Research Note: Growth promoting potential in Mstn mutant quail dependent and independent of increased egg size.

In avian species, positive relationships between egg weight (EW) and body weight (BW) have been reported. However, the correlation between the body growth rate and different weights of eggs from genetically mutated avian species was not studied yet. Myostatin (Mstn), an anti-myogenic factor, mutant quail were recently developed, and it was reported that EW produced from Mstn homozygous mutant quail (HO) was heavier compared to those from wild-type quail (WT). In the current study, distributions of pre-incubated EW and associations between EW and BW were compared between the Mstn mutant and WT quail lines. Average egg weight for the HO group was significantly heavier than the WT (P < 0.001) and the number of eggs having heavier EW (over 11 g) was higher in the HO compared to the WT (P < 0.01). BWs at wk (W) 0, 4, and 6 after hatch were also significantly greater in the HO (P < 0.001 in all groups). In addition, linear regression analyses revealed positive relationships between EW and BW from W0 to W6, regardless of sexes and genotypes. Furthermore, Mstn mutant quail were a heavier BW compared to the WT quail originated from eggs with similar weights. These data indicate that increased BW by Mstn mutation is contributed by increased EW and/or growth promoting activity of Mstn mutation independent of increasing egg sizes. These findings provide Mstn as a desirable genetic factor for selection of poultry breeds with superior growth. In addition, the knowledge gained from this study could inspire similar proof-of-concept studies involving standard and commercial lines of poultry.

Stereotactic Ablative Radiotherapy for Oligometastatic Hepatocellular Carcinoma: A Multi-Institutional Retrospective Study (KROG 20-04).

We investigated the clinical efficacy of stereotactic ablative radiotherapy (SABR) in patients with oligometastatic hepatocellular carcinoma (HCC). The inclusion criteria were patients receiving definitive treatment for HCC with 1−5 metastatic lesions, <3 metastases in a single organ and receiving radiotherapy with fraction doses ≥6 Gy. A total of 100 patients with 121 metastatic lesions were reviewed. The most common site of metastasis was the bones (40%), followed by the lungs (38%). Systemic therapy was administered to 71% of patients. With a median follow-up of 13 months, the median overall survival (OS) was 16 months. The 2-year OS rate was 40%. The prognostic factors in univariate analysis were performance status, Child−Pugh class, primary HCC status, and time interval of metastasis. Performance status and Child−Pugh class remained in multivariate analysis. OS differed significantly depending on the number of prognostic factors: 46 months in patients with both factors (Group 1), 13 months with one factor (Group 2), and 6 months with no risk factor (Group 3) (p < 0.001). Nine patients experienced grade 1 radiation pneumonitis. Given its efficacy and safety, SABR deserves active consideration in the treatment of oligometastatic HCC.

Effects of serum aspartate aminotransferase activity on levels of serum Ca2+, Ca2+ channel genes, apoptotic factors, and meat quality characteristics of chicken pectoralis major muscle.

This study investigated the association between serum aspartate aminotransferase activity and apoptotic potentials assessed by the levels of serum parameters, including Ca2+ and serotonin, Ca2+ channel genes, and caspase genes, at the early postmortem. Additionally, the effect of serum aspartate aminotransferase activity on meat and sensory quality characteristics of chicken pectoralis major muscle was investigated to determine the cause of meat quality deterioration. Among the groups categorized by serum aspartate aminotransferase activity, the high group showed a higher serotonin level and a lower Ca2+ level than the low and medium groups (P < 0.05). The low group had higher apoptotic potentials as exhibited higher levels of ryanodine receptor, sarco/endoplasmic reticulum Ca2+-ATPase, and caspases than the high group (P < 0.05). The low and medium groups showed lower pH24 h and paler surface color than the high group (P < 0.05), indicating pale, soft, and exudative-like meat. Sensory juiciness and overall acceptability were higher in the high group than in the low group (P < 0.05). Overall, serum aspartate aminotransferase activity may be a useful indicator for explaining the meat quality variation, as this molecule can prevent deterioration of chicken meat quality.

Research Note: PSE condition is associated with increased apoptotic potential in broiler pectoralis major muscle.

This study compared the meat quality and sensory quality characteristics of broiler pectoralis major (PM) muscle between meat quality classes, including reddish, firm, and non-exudative (RFN) and pale, soft, and exudative (PSE) conditions. Additionally, we also investigated the associations between the meat quality classes and expression levels of cytochrome c, initiator (caspase 9), and effector caspases (caspase 3 and 7) at the early postmortem period. A total of 135 PM muscles from broilers were used, and meat quality classes were determined according to the pH24 h and lightness values and classified into the RFN (N = 81) and PSE (N = 54) conditions. The PSE breasts showed lower muscle pH15 min and pH24 h values compared to the RFN breasts (P < 0.05). A lower lightness value was observed in the RFN group compared to the PSE group (P < 0.001), whereas there were no significant differences in redness and yellowness between the groups (P > 0.05). The PSE group exhibited higher extent of water loss, including drip loss and cooking loss, compared to the RFN group (P < 0.05). For these reasons, samples from the RFN group required less force to breakdown the cooked meat with more moisture in the mouth after chewing compared to samples from the PSE group (P < 0.001); however, flavor intensity did not differ between the groups (P > 0.05). At 15 min postmortem, all apoptosis-related molecules, including cytochrome c, caspase 9, caspase 3, and caspase 7, were present at higher levels in the PSE group than in the RFN group (P < 0.05). These results indicated that higher apoptotic potentials were associated with the development of PSE chicken breasts. Therefore, the variation of meat quality in chicken breast can be explained as being affected by the expression levels of apoptosis-related factors at the early postmortem period.

Real-Time Monitoring the Effects of Storage Conditions on Volatile Compounds and Quality Indexes of Halal-Certified Kimchi during Distribution Using Electronic Nose.

The food logistics system is an essential sector for maintaining and monitoring the safety and quality of food products and becoming more crucial, especially during and after the pandemic of COVID-19. Kimchi is a popular traditional fermented food originally from Korea and easily changes because of the storage conditions. This study aims to evaluate the effects and the contributions of temperature to volatile compounds, quality indexes, and the shelf life of Halal-certified Kimchi, and to identify alcohol and find the correlation between the identified variables using an electronic nose and conventional method with the integration of multivariate analysis. Thirty-two volatile compounds (VOCs) were detected and correlated with pH, titratable acidity (TA), and lactic acid bacteria (LAB) counts during storage time. Ethanol was also found in the ripened Kimchi and possibly became the critical point of halal Kimchi products besides total acidity, pH, and LAB. Furthermore, the correlation between pH and benzaldehyde, titratable acidity and 3-methylbutanoic acid, and among lactic acid bacteria with ethanol, acetic acid, ethyl acetate, and 3-methylbutanoic acid properly can be used as a given set of variables in the prediction of food quality during storage and distribution.

Association of Serum Glucose, Serotonin, Aspartate Aminotransferase, and Calcium Levels with Meat Quality and Palatability Characteristics of Broiler Pectoralis Major Muscle.

This study investigated the correlations between apoptosis-related blood biochemical parameters measured at exsanguination and the meat and sensory quality characteristics of broiler pectoralis major muscle. The concentration of serotonin showed a positive correlation with aspartate aminotransferase (AST) activity (p < 0.001) and a negative correlation with calcium content (p < 0.01). All serum parameters showed relationships with muscle pH at 15 min and/or 24 h postmortem (p < 0.05). Serum AST activity, which had a negative correlation with calcium content (p < 0.01), was positively related with muscle pH and negatively correlated with Warner−Bratzler shear force values (WBS, p < 0.05). Principal component analysis results revealed the associations between AST activity and meat quality traits, including pH24h, lightness, and WBS. Furthermore, cooked breast with higher AST activity and lower calcium level tended to exhibit higher scores of tenderness and overall acceptability than that with lower AST activity and higher calcium level (p < 0.05).

Generation of αMHC-EGFP knock-in in human pluripotent stem cell line, SNUe003-A-3 using CRISPR/Cas9-based gene targeting.

The cardiac muscle-specific protein, α-myosin heavy chain (αMHC), is a major component of cardiac muscle filaments involved in cardiac muscle contraction. Here, we established an αMHC-enhanced fluorescent protein (EGFP) knock-in human pluripotent stem cell (hPSC) line by linking the EGFP gene to the C-terminal region of αMHC via a 2A non-joining peptide using CRISPR/Cas9 nuclease. The EGFP reporter precisely reflected the endogenous level of αMHC upon the induction of cardiac differentiation. This reporter cell line will be a valuable platform for cardiotoxicity tests, drug screening, and investigating the pathological mechanisms of cardiomyocytes.

Differential Expression of MSTN Isoforms in Muscle between Broiler and Layer Chickens.

Myostatin (Mstn)-A, the main isoform among Mstn splicing variants, functions as a negative regulator, whereas Mstn-B functions as a positive regulator in muscle development. Because broiler chickens are a fast-growing breed raised for meat production and layer chickens are a slow-growing breed raised for egg production, differences in the expression of Mstn isoforms between the two distinct breeds were analyzed in this study. There was no difference in the expression levels of total Mstn (Mstn-A and -B forms) during embryonic development and at D33 between the two breeds. Interestingly, the ratios of Mstn-B to -A were significantly higher in the broiler compared to the layer at most ages. In pectoralis major muscle (PM) tissue, the cross-sectional area (CSA) of muscle fiber was significantly greater in the broiler. The broiler also showed greater bundle CSA and a similar fiber number per bundle compared to the layer at D5 and D33. These data suggest that the greater bundle CSA with myofiber hypertrophy in the broilers is associated with greater muscle growth. The relationship between the expression of Mstn isoforms and growth rate can be used as a potential genetic marker for the selection of higher muscle growth in chickens.

Associations of Apoptotic and Anti-Apoptotic Factors with Beef Quality, Histochemical Characteristics, and Palatability of Hanwoo Longissimus thoracis Muscle.

This study compared the meat quality, histochemical traits, palatability, and expression levels of apoptotic (cytochrome c and caspases) and anti-apoptotic (small heat shock proteins) factors at 45 min and 24 h post-mortem of Hanwoo Longissimus thoracis muscles in groups categorized by Warner-Bratzler shear force (WBS) values to investigate the association between beef tenderness variation and apoptosis-related molecules. There were no differences in marbling scores, meat quality traits, or histochemical characteristics among the WBS groups (p > 0.05) indicating no significant effect on the tenderness variation in the current study. On the other hand, the low group exhibited higher levels of apoptotic and anti-apoptotic factors (except for αß-crystallin) at 45 min post-mortem compared to the high WBS group, resulting in higher scores of tenderness attributes (p < 0.05). However, the level of αß-crystallin at 45 min post-mortem was lower in the low and medium WBS groups compared to the high WBS group (p < 0.0106). At 24 h post-mortem, no significant differences were observed in the expression levels of apoptosis-related factors among the WBS groups (p > 0.05) except for heat shock protein 27 (p < 0.05).

Density-Dependent Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Hormone-Releasing Cells.

Mesenchymal stem cells (MSCs) can differentiate into endoderm lineages, especially parathyroid-hormone (PTH)-releasing cells. We have previously reported that tonsil-derived MSC (T-MSC) can differentiate into PTH-releasing cells (T-MSC-PTHCs), which restored the parathyroid functions in parathyroidectomy (PTX) rats. In this study, we demonstrate quality optimization by standardizing the differentiation rate for a better clinical application of T-MSC-PTHCs to overcome donor-dependent variation of T-MSCs. Quantitation results of PTH mRNA copy number in the differentiated cells and the PTH concentration in the conditioned medium confirmed that the differentiation efficiency largely varied depending on the cells from each donor. In addition, the differentiation rate of the cells from all the donors greatly improved when differentiation was started at a high cell density (100% confluence). The large-scale expression profiling of T-MSC-PTHCs by RNA sequencing indicated that those genes involved in exiting the differentiation and the cell cycle were the major pathways for the differentiation of T-MSC-PTHCs. Furthermore, the implantation of the T-MSC-PTHCs, which were differentiated at a high cell density embedded in hyaluronic acid, resulted in a higher serum PTH in the PTX model. This standardized efficiency of differentiation into PTHC was achieved by initiating differentiation at a high cell density. Our findings provide a potential solution to overcome the limitations due to donor-dependent variation by establishing a standardized differentiation protocol for the clinical application of T-MSC therapy in treating hypoparathyroidism.