Natural overexpression of CAROTENOID CLEAVAGE DIOXYGENASE 4 in tomato alters carotenoid flux.

Carotenoids and apocarotenoids function as pigments and flavor volatiles in plants that enhance consumer appeal and offer health benefits. Tomato (Solanum lycopersicum.) fruit, especially those of wild species, exhibit a high degree of natural variation in carotenoid and apocarotenoid contents. Using positional cloning and an introgression line (IL) of Solanum habrochaites "LA1777', IL8A, we identified carotenoid cleavage dioxygenase 4 (CCD4) as the factor responsible for controlling the dark orange fruit color. CCD4b expression in ripe fruit of IL8A plants was ∼8,000 times greater than that in the wild type, presumably due to 5' cis-regulatory changes. The ShCCD4b-GFP fusion protein localized in the plastid. Phytoene, ζ-carotene, and neurosporene levels increased in ShCCD4b-overexpressing ripe fruit, whereas trans-lycopene, ß-carotene, and lutein levels were reduced, suggestive of feedback regulation in the carotenoid pathway by an unknown apocarotenoid. Solid-phase microextraction-gas chromatography-mass spectrometry analysis showed increased levels of geranylacetone and ß-ionone in ShCCD4b-overexpressing ripe fruit coupled with a ß-cyclocitral deficiency. In carotenoid-accumulating Escherichia coli strains, ShCCD4b cleaved both ζ-carotene and ß-carotene at the C9-C10 (C9'-C10') positions to produce geranylacetone and ß-ionone, respectively. Exogenous ß-cyclocitral decreased carotenoid synthesis in the ripening fruit of tomato and pepper (Capsicum annuum), suggesting feedback inhibition in the pathway. Our findings will be helpful for enhancing the aesthetic and nutritional value of tomato and for understanding the complex regulatory mechanisms of carotenoid and apocarotenoid biogenesis.

Effects of carrier solutions on the viability and efficacy of canine adipose-derived mesenchymal stem cells.

BACKGROUND: Mesenchymal stem cells (MSCs) have favorable characteristics that render them a potent therapeutic tool. We tested the characteristics of MSCs after temporal storage in various carrier solutions, such as 0.9% saline (saline), 5% dextrose solution (DS), heparin in saline, and Hartmann's solution, all of which are approved by the U.S. Food and Drug Administration (FDA). Phosphate-buffered saline, which does not have FDA approval, was also used as a carrier solution. We aimed to examine the effects of these solutions on the viability and characteristics of MSCs to evaluate their suitability and efficacy for the storage of canine adipose-derived MSCs (cADMSCs). RESULTS: We stored the cADMSCs in the test carrier solutions in a time-dependent manner (1, 6, and 12 h) at 4 °C, and analyzed cell confluency, viability, proliferation, self-renewability, and chondrogenic differentiation. Cell confluency was significantly higher in 5% DS and lower in phosphate-buffered saline at 12 h compared to other solutions. cADMSCs stored in saline for 12 h showed the highest viability rate. However, at 12 h, the proliferation rate of cADMSCs was significantly higher after storage in 5% DS and significantly lower after storage in saline, compared to the other solutions. cADMSCs stored in heparin in saline showed superior chondrogenic capacities at 12 h compared to other carrier solutions. The expression levels of the stemness markers, Nanog and Sox2, as well as those of the MSC surface markers, CD90 and CD105, were also affected over time. CONCLUSION: Our results suggest that MSCs should be stored in saline, 5% DS, heparin in saline, or Hartmann's solution at 4 °C, all of which have FDA approval (preferable storage conditions: less than 6 h and no longer than 12 h), rather than storing them in phosphate-buffered saline to ensure high viability and efficacy.

Prior pregnancy complications and maternal cardiovascular disease in young Korean women within 10 years after pregnancy.

BACKGROUND: This study aimed to compare obstetric outcomes in Korean women with and without future cardiovascular disease (CVD) within 10 years after pregnancy, and assessed whether pregnancy complications are independent risk factors, and whether the combination of pregnancy complications has an additive function for risk factors for CVD. METHODS: This was a nationwide population-based study combining the database of the Korea National Health Insurance claims and National Health Screening Programs to assess preeclampsia, low birth weight (LBW), and preterm delivery as risk factors for CVD. Cox proportional hazards models was used to evaluate the risk of total CVD, ischemic heart disease (IHD), and stroke after the pregnancy complications, with adjustment for potential confounding variables. RESULTS: Women with CVD were likely to have a higher prevalence of pregnancy complications than women without CVD. The risk of total CVD was associated with preeclampsia (adjusted hazard ratio (HR), 1.60 [95% confidence interval (CI) 1.50-1.72]), LBW (1.20 [1.12-1.28]), and preterm delivery (1.32 [1.22-1.42]), after adjustment for confounders, including cardiovascular risk factors before pregnancy. The risk estimates of pregnancy complications for IHD were higher than those for stroke. In this study, the risk of total CVD was higher in the combined presence of preeclampsia and preterm delivery (2.23 [1.57-3.17] or all three complications (2.06 [1.76-2.40]), relative to no complications. The highest HR was noted in the risk of all pregnancy complications for IHD (2.39 [1.98-2.89]). CONCLUSION: Preeclampsia, preterm delivery, and LBW were independently associated with CVD in young Korean women. In addition, the combination of pregnancy complications had less-than-additive effects on CVD incidence.

Increased prevalence rate of metabolic syndrome is an independent predictor of cardiovascular disease in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: We investigated the prevalence of metabolic syndrome (MetS) in all or nonobese patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and compared it with age- and gender-matched controls. Also, we assessed the effect of variables at diagnosis on the risk of cardiovascular disease (CVD) in all or nonobese AAV patients. METHODS: In this study, 173 AAV patients and 344 controls were included and MetS was defined by the National Cholesterol Education Program Adults Treatment Panel III criteria. The obesity based on body mass index (BMI) was defined as BMI ≥ 25 kg/m2. The follow-up duration was defined as the period from diagnosis to the last visit or to each poor outcome occurrence. RESULTS: The median age of AAV patients was 58.7 years and 57 patients were men. The prevalence of MetS was 50.9% in all AAV patients and 46.5% in nonobese AAV patients, which were significantly higher than 37.8% in all controls and 28.2% in nonobese controls. In Kaplan-Meier survival analysis, Mets at diagnosis significantly reduced the cumulative CVD-free survival rate in both all and nonobese AAV patients. In the multivariable Cox hazards model analysis, CVD during follow-up was significantly associated with both Birmingham vasculitis activity score (BVAS) (HR 1.159) and MetS at diagnosis (HR 9.036) in nonobese AAV patients. CONCLUSIONS: The prevalence of MetS at diagnosis in all or nonobese AAV patients was significantly higher than those in all or nonobese controls. Furthermore, both BVAS and MetS at diagnosis increased the risk of CVD in nonobese AAV patients.

Invasive dental procedures as risk factors for postoperative spinal infection and the effect of antibiotic prophylaxis.

AIM: To identify invasive dental procedures as a risk factor for postoperative spinal infection (PSI) and evaluate the effectiveness of antibiotic prophylaxis. MATERIALS AND METHODS: We analysed 229,335 patients who underwent spinal surgery with instrumentation from 2010 to 2017, using the nationwide database. The incidence of spinal infection 2 years after surgery was determined. Invasive dental procedures as a risk factor for PSI and the effects of antibiotic prophylaxis during this period were also analysed. RESULTS: A total of 15,346 patients (6.69%) were diagnosed with PSI. It was found that advanced age, male sex, and a high Charlson Comorbidity Index were risk factors for PSI. The risk of PSI did not increase following dental procedures (adjusted hazard ratio [HR] 0.850; 95% confidence interval [CI], 0.793-0.912) and was not affected by antibiotics (adjusted HR 1.097; 95% CI, 0.987-1.218). Patients who received dental treatment as early as 3 months after spinal surgery had the lowest risk of postoperative infection (adjusted HR 0.869; 95% CI, 0.795-0.950). CONCLUSIONS: Invasive dental procedure does not increase the risk of PSI, and antibiotic prophylaxis before dental procedure was not effective in preventing spinal infection.

Women with multiple gestations have an increased risk of development of hypertension in the future.

BACKGROUND: Multiple gestations are associated with an increased incidence of preeclampsia. However, there exists no evidence for an association between multiple gestations and development of hypertension(HTN) later in life. This study aimed to determine whether multiple gestations are associated with HTN beyond the peripartum period. METHODS: In this retrospective nationwide population-based study, women who delivered a baby between January 1, 2007, and December 31, 2008, and underwent a national health screening examination within one year prior to their pregnancy were included. Subsequently, we tracked the occurrence of HTN during follow-up until December 31, 2015, using International Classification of Diseases-10th Revision codes. RESULTS: Among 362,821 women who gave birth during the study period, 4,944 (1.36%) women had multiple gestations. The cumulative incidence of HTN was higher in multiple gestations group compared with singleton group (5.95% vs. 3.78%, p < 0.01, respectively). On the Cox proportional hazards models, the risk of HTN was increased in women with multiple gestations (HR 1.35, 95% CI 1.19, 1.54) compared with those with singleton after adjustment for age, primiparity, preeclampsia, atrial fibrillation, body mass index, blood pressure, diabetes mellitus, high total cholesterol, abnormal liver function test, regular exercise, and smoking status. CONCLUSIONS: Multiple gestations are associated with an increased risk of HTN later in life. Therefore, guidelines for the management of high-risk patients after delivery should be established.

Is There an Association Between Psychiatric Disorders and Adolescent Idiopathic Scoliosis? A Large-database Study.

BACKGROUND: Children with adolescent idiopathic scoliosis (AIS) have reduced quality of life related to poor self-image, perhaps because of cosmetic concerns. However, there has not been a large-database epidemiologic study on the association between psychiatric disorders and scoliosis. QUESTIONS/PURPOSES: Using the Korean National Health Insurance database, we asked: (1) How common are psychiatric disorders among children with AIS? (2) After controlling for gender, age, insurance type, and residential district, are psychiatric disorders more common among children with AIS than among age-matched controls? METHODS: A retrospective analysis was conducted using sample datasets from the Health Insurance Review and Assessment Service from 2012 to 2016, which is a 10% randomly extracted sample of total inpatients and outpatients each year. The mean number of total patients in each dataset was 1,047,603 ± 34,534. The mean number of children with AIS was 7409 ± 158 for each year. The age criteria was 10 to 19 years for the matching. Mood disorders, anxiety disorders, and behavioral disorders were selected as disorders possibly associated with AIS. We identified children with AIS who had any of the disorders above, and we obtained the prevalence of these disorders based on diagnostic codes. As an exploratory analysis, clinically meaningful variables were selected among the available codes in the dataset, and a univariable logistic regression test was performed for each variable. A multivariable logistic regression test with advanced variables was performed to identify the adjusted odds ratios of psychiatric disorders in children with AIS. RESULTS: The median (range) prevalence of psychiatric disorders in children with AIS from 2012 to 2016 was 7% (6% to 7%). Compared with children who did not have AIS, and after controlling for gender, age, insurance type, and residential district, children with AIS were more likely to have psychiatric disorders in all 5 years. The adjusted ORs of psychiatric disorders in children with AIS compared with children who did not have AIS ranged from 1.47 to 1.74 (2012: OR 1.60 [95% CI 1.46 to 1.75]; p < 0.001; 2013: OR 1.73 [95% CI 1.58 to 1.89]; p < 0.001; 2014: OR 1.74 [95% CI 1.59 to 1.91]; p < 0.001; 2015: OR 1.71 [95% CI 1.56 to 1.88]; p < 0.001; 2016: OR 1.47 [95% CI 1.33 to 1.62]; p < 0.001). CONCLUSION: Considering the higher prevalence of psychiatric disorders in children with AIS compared with children who did not have AIS, children with AIS and their parents should be counseled about the increased risk of deteriorating mental health of the patients, and surgeons should provide early referral to pediatric psychiatrists. Further studies should investigate the effect of the factors related to AIS, such as curve type, Cobb angle, and treatment modality. LEVEL OF EVIDENCE: Level III, prognostic study.

Which Factors Affect the Stress of Intraoperative Orthopedic Surgeons by Using Electroencephalography Signals and Heart Rate Variability?

Can we recognize intraoperative real-time stress of orthopedic surgeons and which factors affect the stress of intraoperative orthopedic surgeons with EEG and HRV? From June 2018 to November 2018, 265 consecutive records of intraoperative stress measures for orthopedic surgeons were compared. Intraoperative EEG waves and HRV, comprising beats per minute (BPM) and low frequency (LF)/high frequency (HF) ratio were gathered for stress-associated parameters. Differences in stress parameters according to the experience of surgeons, intraoperative blood loss, and operation time depending on whether or not a tourniquet were investigated. Stress-associated EEG signals including beta 3 waves were significantly higher compared to EEG at rest for novice surgeons as the procedure progressed. Among senior surgeons, the LF/HF ratio reflecting the physical demands of stress was higher than that of novice surgeons at all stages. In surgeries including tourniquets, operation time was positively correlated with stress parameters including beta 1, beta 2, beta 3 waves and BPM. In non-tourniquet orthopedic surgeries, intraoperative blood loss was positively correlated with beta 1, beta 2, and beta 3 waves. Among orthopedic surgeons, those with less experience demonstrated relatively higher levels of stress during surgery. Prolonged operation time or excessive intraoperative blood loss appear to be contributing factors that increase stress.

Effects of endogenous and exogenous oestrogen exposure on hearing level in postmenopausal women: A cross-sectional study.

OBJECTIVE: To investigate the effect of endogenous and exogenous oestrogen exposure on hearing levels in postmenopausal women. STUDY DESIGN: Retrospective cross-sectional study. SETTING: Population-based survey data collected by the Korean National Health and Nutrition Survey between 1 January 2010 and 31 December 2012. SUBJECTS AND METHODS: Participants comprised 3653 postmenopausal women. Detailed histories for reproductive factors and data on the use of hormone replacement therapy were obtained through health questionnaires and otologic examinations, including pure-tone audiogram and otoscopic findings. Complex-sample linear regression models controlling for confounding factors were generated to determine whether hormone-related factors were associated with hearing loss. RESULTS: Women who experienced a longer duration of oestrogen exposure had better hearing compared to those who do not in multivariate model adjusting for confounding factors with a lower adjusted beta coefficient of hearing threshold (ß = -0.18, 95% confidence interval = -0.3 to -0.07, P = .002). The results also suggested that hormone replacement therapy may be beneficial for attenuating hearing loss (ß = -1.22, 95% confidence interval = -2.19 to -0.25, P = .014), particularly in the high-frequency range from 3 to 6 KHz. CONCLUSION: A longer duration of lifetime oestrogen exposure (LEE) and the use of hormone replacement therapy are likely to attenuate hearing loss. These epidemiologic data provide evidence that oestrogen may be beneficial for attenuating age-related hearing decline.

Genetic mapping of the c1 locus by GBS-based BSA-seq revealed Pseudo-Response Regulator 2 as a candidate gene controlling pepper fruit color.

KEY MESSAGE: The Pseudo-Response Regulator 2 gene was identified in the c1 locus, representing a genetic factor regulating fruit color in pepper using GBS-based BSA-seq. The loci c1, c2, and y have been widely reported as genetic determinants of various ripe fruit colors in pepper. However, c1, which may impact reduced pigmentation in red, orange, and yellow fruits, is not well understood. Two cultivars showing peach or orange fruit in Capsicum chinense 'Habanero' were found to have c2 mutation and were hypothesized to segregate c1 locus in the F2 population. Habanero peach (HP) showed a reduced level of chlorophylls, carotenoids and total soluble solids in immature and ripe fruits. A microscopic examination of the fruit pericarps revealed smaller plastids and less stacked thylakoid grana in HP. The expression of many genes related to chlorophyll and carotenoid biosynthetic pathways were reduced in HP. To identify the genomic region of the c1 locus, bulked segregant analysis combined with genotyping-by-sequencing was employed on an F2 population derived from a cross between Habanero orange and HP. One SNP at chromosome 1 was strongly associated with the peach fruit color. Pepper Pseudo-Response Regulator 2 (PRR2) was located close to the SNP and cosegregated with the peach fruit color. A 41 bp deletion at the third exon-intron junction region of CcPRR2 in HP resulted in a premature termination codon. A nonsense mutation of CaPRR2 was found in C. annuum 'IT158782' which had white ripe fruit coupled with null mutations of capsanthin-capsorubin synthase (y) and phytoene synthase 1 (c2). These results will be useful for the genetic improvement in fruit color and nutritional quality in pepper.

Can antineutrophil cytoplasmic antibody positivity at diagnosis predict the poor outcomes of Sjögren's syndrome?

We investigated the clinical implication of ANCA positivity at diagnosis on the poor outcomes in patients with Sjögren's syndrome. The medical records of 606 Korean patients with Sjögren's syndrome were retrospectively reviewed. The results of perinuclear (P)-ANCA, myeloperoxidase (MPO)-ANCA, cytoplasmic (C)-ANCA, and proteinase 3 (PR3)-ANCA were collected and the frequencies of all-cause mortality, interstitial lung disease (ILD), end-stage renal disease (ESRD), and lymphoma were assessed as the poor outcomes of Sjögren's syndrome. Comparison of the cumulative patient survivals between the two groups was analysed by the Kaplan-Meier survival analysis. Of the 606 patients, ANCA was detected in 10.2% of Sjögren's syndrome patients without AAV. Twenty-one patients (3.5%) died, 99 patients (16.3%) suffered from ILD, and 8 patients had ESRD. Lymphoma occurred in 5 patients (0.8%) during 37.5 months. Sjögren's syndrome patients with ANCA positivity exhibited a lower cumulative ILD-free survival rate than those with ANCA negativity (P = 0.001). Sjögren's syndrome patients with P-ANCA positivity and those with MPO-ANCA (or P-ANCA) positivity showed a lower cumulative ILD-free survival rate than those without (P = 0.012 and P < 0.001). Also, Sjögren's syndrome patients with P-ANCA positivity exhibited a lower cumulative ESRD-free survival rate than those without (P = 0.043). ANCA positivity was associated with neither all-cause mortality nor lymphoma in Sjögren's syndrome patients. ANCA positivity and MPO-ANCA (or P-ANCA) positivity at diagnosis was associated with the development of ILD during follow-up in patients with Sjögren's syndrome.

Clinical significance of ANCA positivity in patients with IgA vasculitis: a retrospective monocentric study.

We assessed the detection rate of antineutrophil cytoplasmic antibody (ANCA) and investigated the clinical significance of ANCA positivity at diagnosis in patients with IgA vasculitis (Henoch-Schönlein purpura). We retrospectively reviewed their medical records of 86 IgA vasculitis patients. We divided IgA vasculitis patients based on ANCA positivity and compared variables at diagnosis and poor outcomes and medication during follow-up between the two groups. All-cause mortality, relapse, chronic kidney disease (CKD) (stage 3-5) and end-stage renal disease (ESRD) were defined as poor outcomes. We assessed the renal histological features based on the International Study of Kidney Disease in Children (ISKDC) classification and Oxford classification. Comparison of cumulative survivals was analysed by the Kaplan-Meier survival analysis. Five of 86 IgA vasculitis patients (5.8%) had ANCA and all ANCA-positive patients had myeloperoxidase (MPO)-ANCA. IgA vasculitis patients with ANCA exhibited pulmonary and nervous involvement of IgA vasculitis more frequently than those without. There was no significant difference in renal involvement between the two groups. There were no significant differences in renal histological features and poor outcomes related to renal function between IgA vasculitis patients with and without ANCA. In addition, 5 IgA vasculitis patients did not meet the classification criteria for ANCA-associated vasculitis (AAV). Particularly, there were no significant differences in CKD and ESRD-free survival rates between IgA vasculitis patients with and without ANCA. 5.8% of IgA vasculitis patients had MPO-ANCA and poor outcomes of IgA vasculitis were not affected by the presence of ANCA.

Production of Mesenchymal Stem Cells Through Stem Cell Reprogramming.

Mesenchymal stem cells (MSCs) possess a broad spectrum of therapeutic applications and have been used in clinical trials. MSCs are mainly retrieved from adult or fetal tissues. However, there are many obstacles with the use of tissue-derived MSCs, such as shortages of tissue sources, difficult and invasive retrieval methods, cell population heterogeneity, low purity, cell senescence, and loss of pluripotency and proliferative capacities over continuous passages. Therefore, other methods to obtain high-quality MSCs need to be developed to overcome the limitations of tissue-derived MSCs. Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are considered potent sources for the derivation of MSCs. PSC-derived MSCs (PSC-MSCs) may surpass tissue-derived MSCs in proliferation capacity, immunomodulatory activity, and in vivo therapeutic applications. In this review, we will discuss basic as well as recent protocols for the production of PSC-MSCs and their in vitro and in vivo therapeutic efficacies. A better understanding of the current advances in the production of PSC-MSCs will inspire scientists to devise more efficient differentiation methods that will be a breakthrough in the clinical application of PSC-MSCs.

Association of CDKN2A/CDKN2B with inflammatory bowel disease in Koreans.

BACKGROUND AND AIM: CDKN2A/CDKN2B locus on 9p21 is reported to be associated with various diseases, including cancer and cardiovascular and inflammatory diseases. Significant downregulation of CDKN2B-AS1 in inflamed colon tissue of inflammatory bowel disease (IBD) cases was reported in Europeans. This study aimed to confirm the suggestive association of CDKN2A/CDKN2B with IBD identified in our recent genome-wide association study (GWAS). METHODS: We examined the association of CDKN2A/CDKN2B locus with IBD in an additional sample of 574 IBD cases and 542 controls, totaling 4068 cases and 8074 controls. In silico study was performed at various levels for functional annotation of the causal variant. Co-localization of the GWAS association signals and the corresponding expression quantitative trait loci in IBD-related tissues was evaluated using eCAVIAR. RESULTS: An expanded GWAS showed genome-wide significant association of rs3731257 at 9p21 with IBD (odds ratio = 1.17, 95% confidence interval = 1.12-1.22, Pcombined  = 5.68 × 10-9 ) and Crohn's disease (odds ratio = 1.22, 95% confidence interval = 1.15-1.28, Pcombined  = 8.85 × 10-9 ) in the Korean population. Co-localization study suggested that both CDKN2B-AS1 and CDKN2A might be functionally associated with the locus in the small intestine. CONCLUSIONS: rs3731257 in CDKN2A/CDKN2B is an IBD-susceptible locus in Koreans, with a suggestive role for small intestine-specific gene regulation. Our findings suggested that alterations of the CDKN2A/CDKN2B locus could affect the pathophysiology of IBD.

Silver Nanoparticles: Two-Faced Neuronal Differentiation-Inducing Material in Neuroblastoma (SH-SY5Y) Cells.

We have previously demonstrated the potential of biologically synthesized silver nanoparticles (AgNP) in the induction of neuronal differentiation of human neuroblastoma, SH-SY5Y cells; we aimed herein to unveil its molecular mechanism in comparison to the well-known neuronal differentiation-inducing agent, all-trans-retinoic acid (RA). AgNP-treated SH-SY5Y cells showed significantly higher reactive oxygen species (ROS) generation, stronger mitochondrial membrane depolarization, lower dual-specificity phosphatase expression, higher extracellular-signal-regulated kinase (ERK) phosphorylation, lower AKT phosphorylation, and lower expression of the genes encoding the antioxidant enzymes than RA-treated cells. Notably, pretreatment with N-acetyl-l-cysteine significantly abolished AgNP-induced neuronal differentiation, but not in that induced by RA. ERK inhibition, but not AKT inhibition, suppresses neurite growth that is induced by AgNP. Taken together, our results uncover the pivotal contribution of ROS in the AgNP-induced neuronal differentiation mechanism, which is different from that of RA. However, the negative consequence of AgNP-induced neurite growth may be high ROS generation and the downregulation of the expression of the genes encoding the antioxidant enzymes, which prompts the future consideration and an in-depth study of the application of AgNP-differentiated cells in neurodegenerative disease therapy.

Correlation between Oxidative Stress, Nutrition, and Cancer Initiation.

Inadequate or excessive nutrient consumption leads to oxidative stress, which may disrupt oxidative homeostasis, activate a cascade of molecular pathways, and alter the metabolic status of various tissues. Several foods and consumption patterns have been associated with various cancers and approximately 30-35% of the cancer cases are correlated with overnutrition or malnutrition. However, several contradictory studies are available regarding the association between diet and cancer risk, which remains to be elucidated. Concurrently, oxidative stress is a crucial factor for cancer progression and therapy. Nutritional oxidative stress may be induced by an imbalance between antioxidant defense and pro-oxidant load due to inadequate or excess nutrient supply. Oxidative stress is a physiological state where high levels of reactive oxygen species (ROS) and free radicals are generated. Several signaling pathways associated with carcinogenesis can additionally control ROS generation and regulate ROS downstream mechanisms, which could have potential implications in anticancer research. Cancer initiation may be modulated by the nutrition-mediated elevation in ROS levels, which can stimulate cancer initiation by triggering DNA mutations, damage, and pro-oncogenic signaling. Therefore, in this review, we have provided an overview of the relationship between nutrition, oxidative stress, and cancer initiation, and evaluated the impact of nutrient-mediated regulation of antioxidant capability against cancer therapy.

The Role of Reactive Oxygen Species (ROS) in the Biological Activities of Metallic Nanoparticles.

Nanoparticles (NPs) possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS). The amount of ROS produced by metallic NPs correlates with particle size, shape, surface area, and chemistry. ROS possess multiple functions in cellular biology, with ROS generation a key factor in metallic NP-induced toxicity, as well as modulation of cellular signaling involved in cell death, proliferation, and differentiation. In this review, we briefly explained NP classes and their biomedical applications and describe the sources and roles of ROS in NP-related biological functions in vitro and in vivo. Furthermore, we also described the roles of metal NP-induced ROS generation in stem cell biology. Although the roles of ROS in metallic NP-related biological functions requires further investigation, modulation and characterization of metallic NP-induced ROS production are promising in the application of metallic NPs in the areas of regenerative medicine and medical devices.

Expandable Cages for Lumbar Interbody Fusion: A Narrative Review.

Lumbar fusion surgery for treating degenerative spinal diseases has undergone significant advancements in recent years. In addition to posterior instrumentation, anterior interbody fusion techniques have been developed along with various cages for interbody fusion. Recently, expandable cages capable of altering height, lordotic angle, and footprint within the disc space have garnered significant attention. In this manuscript, we review the current status, clinical outcomes, and future prospects of expandable cages for lumbar interbody fusion based on the existing literature. Expandable cages are suitable for minimally invasive spinal surgeries. Small-sized cages can be inserted and subsequently expanded to a larger size within the disc space. While expandable cages generally demonstrate superior clinical outcomes compared to static cages, some studies have suggested comparable or even poorer outcomes with expandable cages than static cages. Careful interpretation through additional long-term follow-ups is required to assess the utility of expandable cages. If these shortcomings are addressed and the advantages are further developed, expandable cages could become suitable surgical instruments for minimally invasive spinal surgeries.

Pre-mixing of omega-3 fatty acid-containing liposomes enhances the drug release rate and therapeutic efficacy of anticancer drugs loaded in liposomes.

The therapeutic efficacy of anticancer drugs loaded in liposomes composed of rigid phosphatidylcholine (PC) is hindered by the limited release of these drugs at the tumor site, which in turn hampers delivery of the drug to its intracellular target. In an attempt to improve the therapeutic efficacy of liposomal anticancer drugs, we here explored the use of empty liposomes as "trigger" vehicles to induce drug release from drug-loaded liposomes through liposome-liposome interactions. Empty liposomes containing PC in which omega-3 fatty acids comprised both fatty acid strands (Omega-L) showed a triggering effect on drug release from doxorubicin (DOX)-loaded liposomes (Caelyx). The effectiveness of this triggered-release effect was dependent on the Omega-L composition as well as the mixing ratio of Omega-L to Caelyx. Cryo-TEM and differential calorimetry studies revealed that the Omega-L effect was associated with liposome-liposome interactions that led to loosened membrane packing and increased fluidity of Caelyx. In cultured cells, the intracellular/intranuclear DOX uptake and anticancer efficacy of Caelyx was greatly improved by Omega-L pre-mixing. Intravenous injection of rats with Caelyx, premixed with Omega-L, decreased the area under the plasma concentration-time curve from time zero to time infinity and increased clearance without significantly changing the mean residence time or terminal half-life of DOX compared with Caelyx alone. Ex vivo bioimaging showed that DOX fluorescence in tumors, but not in other organs, was significantly increased by Omega-L premixing. In the mouse xenograft model, premixing of Omega-L with Caelyx suppressed tumor growth 2.5-fold compared with Caelyx. Collectively, the data provide preliminary evidence that the Omega-L-triggered drug release that occurs before and after dosing, particularly at tumor site, improved the therapeutic efficacy of Caelyx. The simple approach described here could enhance the therapeutic value of Caelyx and other anticancer drug-loaded liposomes.