Is There a Pathologic Running Motion Associated with Running-Related Injuries? A Methodological Study Using a Motion Analysis System Without Sensors.

(1) Background and objectives: Running-related injuries (RRIs) are commonly attributed to improper running posture and overuse. This study aims to analyze the running motions of individuals with and without RRIs using a sensor-free method, which offers a user-friendly and straightforward approach. (2) Materials and Methods: A total of 155 runners were divided into two groups: the normal runner group (runners who had never been injured, n = 50) and the RRI group (runners who had experience at least one injury while running, n = 105). The forward head posture (FHP), trunk lean, hip rotation, horizontal movement of the center of gravity (COG), vertical movement of the COG, pelvic rotation, hip hike, and type of strike were measured for posture analysis. (3) Results: We found that the left-right balance of the pelvis and the spinal posture during running were associated with RRIs. The difference in hip hike and FHP emerged as key predictors of running-related musculoskeletal injury occurrence from our logistic regression analysis. (4) Conclusions: Identifying pathological movements in runners through running motion analysis without the use of sensors can be instrumental in the prevention and treatment of RRIs.

COVID-19 and Neurodevelopmental Delays in Early Childhood: A Longitudinal Analysis of Developmental Outcomes in Korean Children.

This study employed a longitudinal analysis to evaluate the association between the coronavirus disease 2019 pandemic and neurodevelopment by analyzing over 1.8 million children from the Korean Developmental Screening Test for Infants and Children included in South Korea's National Health Screening Program. We compared the developmental outcomes in five age groups-9-17 months, 18-29 months, 30-41 months, 42-53 months, and 54-65 months-between the pre-pandemic (2018-2019) and pandemic (2020-2021) periods. Significant increases in potential developmental delays were observed during the pandemic in communication, cognitive, social interaction, self-care, and fine motor skills across most age groups. All five age groups experienced notable disruptions in communication and fine motor skills. Children from socioeconomically disadvantaged backgrounds faced higher risks across all domains. These findings highlight the need for targeted interventions and continuous monitoring to support the developmental needs of children affected by pandemic-related disruptions.

Phf7 has impacts on the body growth and bone remodeling by regulating testicular hormones in male mice.

PHD finger protein 7 (Phf7) is a member of the PHF family proteins, which plays important roles in spermiogenesis. Phf7 is expressed in the adult testes and its deficiency causes male infertility. In this study, we tried to find the causal relationship between Phf7 deficiency and reduced growth retardation which were found in null knock-out (Phf7-/-) mice. Phf7-/- mice were born normally in the Mendelian ratio. However, the Phf7-/- males showed decreased body weight gain, bone mineral density, and bone mineral content compared to those in wild-type (WT) mice. Histological analysis for tibia revealed increased number of osteoclast cells in Phf7-/- mice compared with that in WT mice. When we analyzed the expressions for marker genes for the initial stage of osteoclastogenesis, such as receptor activator of nuclear factor kappa B (Rank) in tibia, there was no difference in the mRNA levels between Phf7-/- and WT mice. However, the expression of tartrate-resistant acid phosphatase (Trap), a mature stage marker gene, was significantly higher in Phf7-/- mice than in WT mice. In addition, the levels of testosterone and dihydrotestosterone (DHT), more potent and active form of testosterone, were significantly reduced in the testes of Phf7-/- mice compared to those in WT mice. Furthermore, testicular mRNA levels for steroidogenesis marker genes, namely Star, Cyp11a1, Cyp17a1 and 17ß-hsd, were significantly lower in Phf7-/- mice than in WT mice. In conclusion, these results suggest that Phf7 deficiency reduces the production of male sex hormones and thereby impairs associated bone remodeling.

Mediating Effect of Self-Control on the Relationship between Obesity-Related Stress and Weight Control Behavior among Female College Students with Overweight and Obesity.

BACKGROUND: This study aimed to determine whether self-regulation acts as a mediating factor in the relationship between obesity-related stress and weight control behavior, targeting Korean female college students. Obesity-related stress and weight control behaviors are important factors affecting an individual's health and well-being, and self-control, a psychological trait, can play a pivotal role in regulating how individuals respond to stress and engage in weight management behaviors. METHODS: This study employed a descriptive correlational design. A total of 109 female college students with overweight and obesity participated in the study. We used a self-report questionnaire to measure obesity-related stress, self-control, and degree of weight control behavior. Data were analyzed using descriptive statistics, Pearson's correlation coefficient analysis, and bootstrapping using Hayes' PROCESS macro for mediation. RESULTS: Significant relationships between obesity-related stress and weight control behavior (r = 0.25, p < 0.001), obesity-related stress and self-control (r = -0.36, p < 0.001), and weight control behavior and self-control (r = 0.26, p < 0.001) were observed. Self-control showed an indirect mediating effect on the relationship between obesity-related stress and weight control behavior (Β = 0.37, p = 0.001). CONCLUSIONS: Through the research results, it was confirmed that self-control is a factor that has a mediating effect in the relationship between obesity-related stress and weight control behavior among female college students with overweight and obesity. These results underscore the importance of addressing self-control strategies in interventions aimed at promoting healthy weight management among female college students with overweight or obesity.

Factors associated with acute kidney injury among preterm infants administered vancomycin: a retrospective cohort study.

BACKGROUND: Vancomycin (VCM) is a widely used antibiotic for the treatment of gram-positive microorganisms, with some nephrotoxic effects. Recent studies have suggested that piperacillin-tazobactam (TZP) aggravates VCM-induced nephrotoxicity in adults and adolescents. However, there is a lack of research investigating these effects in the newborn population. Therefore, this study investigates whether the concomitant use of TZP with VCM use increases the risk of acute kidney injury (AKI) and to explore the factors associated with AKI in preterm infants treated with VCM. METHODS: This retrospective study included preterm infants with birth weight < 1,500 g in a single tertiary center who were born between 2018 and 2021 and received VCM for a minimum of 3 days. AKI was defined as an increase in serum creatinine (SCr) of at least 0.3 mg/dL and an increase in SCr of at least 1.5 times baseline during and up to 1 week after discontinuation of VCM. The study population was categorized as those with or without concomitant use of TZP. Data on perinatal and postnatal factors associated with AKI were collected and analyzed. RESULTS: Of the 70 infants, 17 died before 7 postnatal days or antecedent AKI and were excluded, while among the remaining participants, 25 received VCM with TZP (VCM + TZP) and 28 VCM without TZP (VCM-TZP). Gestational age (GA) at birth (26.4 ± 2.8 weeks vs. 26.5 ± 2.6 weeks, p = 0.859) and birthweight (750.4 ± 232.2 g vs. 838.1 ± 268.7 g, p = 0.212) were comparable between the two groups. There were no significant differences in the incidence of AKI between groups. Multivariate analysis showed that GA (adjusted OR: 0.58, 95% CI: 0.35-0.98, p = 0.042), patent ductus arteriosus (PDA) (adjusted OR: 5.23, 95% CI: 0.67-41.05, p = 0.115), and necrotizing enterocolitis (NEC) (adjusted OR: 37.65, 95% CI: 3.08-459.96, p = 0.005) were associated with AKI in the study population. CONCLUSIONS: In very low birthweight infants, concomitant use of TZP did not increase the risk of AKI during VCM administration. Instead, a lower GA, and NEC were associated with AKI in this population.

Neonatal and developmental outcomes of very preterm twins according to the chorionicity and weight discordance.

Perinatal outcomes of twin pregnancies are determined by several factors, such as gestational age (GA), chorionicity, and discordance at birth. This retrospective study aimed to investigate the association of chorionicity and discordance with neonatal and neurodevelopmental outcomes in preterm twin infants from uncomplicated pregnancy. Data of very preterm twin infants who were both live-born between 2014 and 2019 on the chorionicity of the twin, diagnosis of the twin-to-twin syndrome (TTTS), weight discordance at birth, and neonatal and neurodevelopmental outcomes at 24 months of corrected age (CA) were collected. Of the 204 twin infants analyzed, 136 were dichorionic (DC) and 68 were monochorionic (MC), including 15 pairs with TTTS. After adjusting for GA, brain injury, including severe intraventricular hemorrhage and periventricular leukomalacia, was mostly found in the MC with TTTS group, with a higher incidence of cerebral palsy and motor delay at CA 24 months. After excluding TTTS, multivariable analysis showed no association between chorionicity and neonatal and developmental outcomes, whereas small infants among co-twins (adjusted odds ratio (aOR) 3.33, 95% confidence interval 1.03-10.74) and greater discordance (%) of weight at birth (aOR 1.04, 1.00-1.07) were associated with neurodevelopmental impairment. Monochorionicity might not determine adverse outcomes among very preterm twins from uncomplicated pregnancy.

Targeting BAP1 with small compound inhibitor for colon cancer treatment.

BRCA1-associated protein-1 (BAP1) is a ubiquitin C-terminal hydrolase domain-containing deubiquitinase. The gene encoding BAP1 is mutated in various human cancers, including mesothelioma, uveal melanoma and renal cell carcinoma. BAP1 plays roles in many cancer-related cellular functions, including cell proliferation, cell death, and nuclear processes crucial for genome stability, such as DNA repair and replication. While these findings suggest that BAP1 functions as a tumor suppressor, recent data also suggest that BAP1 might play tumor-promoting roles in certain cancers, such as breast cancer and hematopoietic malignancies. Here, we show that BAP1 is upregulated in colon cancer cells and tissues and that BAP1 depletion reduces colon cancer cell proliferation and tumor growth. BAP1 contributes to colon cancer cell proliferation by accelerating DNA replication and suppressing replication stress and concomitant apoptosis. A recently identified BAP1 inhibitor, TG2-179-1, which seems to covalently bind to the active site of BAP1, exhibits potent cytotoxic activity against colon cancer cells, with half-maximal inhibitory concentrations of less than 10 µM, and inhibits colon tumor growth. TG2-179-1 exerts cytotoxic activity by targeting BAP1, leading to defective replication and increased apoptosis. This work therefore shows that BAP1 acts oncogenically in colon cancer and is a potential therapeutic target for this cancer. Our work also suggests that TG2-179-1 can be developed as a potential therapeutic agent for colon cancer.

Neurodevelopmental outcomes and volumetric analysis of brain in preterm infants with isolated cerebellar hemorrhage.

Background: Cerebellar hemorrhage (CBH) is a major form of cerebellar injury in preterm infants. We aimed to investigate the risk factors and neurodevelopmental outcomes of isolated CBH and performed volumetric analysis at term-equivalent age. Methods: This single-centered nested case-control study included 26 preterm infants with isolated CBH and 52 infants without isolated CBH and any significant supratentorial injury. Results: Isolated CBH was associated with PCO2 fluctuation within 72 h after birth (adjusted odds ratio 1.007, 95% confidence interval 1.000-1.014). The composite score in the motor domain of the Bayley Scales of Infant and Toddler Development at 24 month of corrected age was lower in the punctate isolated CBH group than that in the control group (85.3 vs. 94.5, P = 0.023). Preterm infants with isolated CBH had smaller cerebellum and pons at term-equivalent age compared to the control group. Isolated CBH with adverse neurodevelopment had a smaller ventral diencephalon and midbrain compared to isolated CBH without adverse neurodevelopmental outcomes. Conclusions: In preterm infants, isolated CBH with punctate lesions were associated with abnormal motor development at 24 months of corrected age. Isolated CBH accompanied by a smaller ventral diencephalon and midbrain at term equivalent had adverse neurodevelopmental outcomes.

Humoral and Cellular Immune Responses to Vector, Mix-and-Match, or mRNA Vaccines against SARS-CoV-2 and the Relationship between the Two Immune Responses.

We investigated how differences in age, sex, or vaccine type can affect humoral and cellular immune responses after vaccination with vector (ChAdOx1 nCoV-19), mix-and-match (first, ChAdOx1 nCoV-19, and second, BNT162b2), or mRNA (BNT162b2 or mRNA-1273) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Venous blood was collected from 573 subjects (vector, 396; mix-and-match, 96; and mRNA, 81) before the first vaccination (T0), 7 to 8 weeks (vector) or 3 to 4 weeks (mRNA) after the first vaccination (T1), and 3 to 4 weeks after the second vaccination (T2). The humoral and cellular immune responses were evaluated using Elecsys anti-SARS-CoV-2 (Roche), Alinity SARS-CoV-2 IgG II Quant (Abbott), cPass SARS-CoV-2 neutralization antibody detection (GenScript), and QuantiFERON SARS-CoV-2 (Qiagen) kits. At T1, the levels of the receptor-binding domain antibodies (RBD Ab) and neutralizing antibodies (NAb) decreased with aging, but interferon gamma release (IGR) levels increased. The RBD Ab, NAb, and IGR levels were higher in females than in males at T1 and T2. The NAb levels were higher in the mix-and-match and mRNA vaccine groups than in the vector vaccine group at T2. The RBD Ab and IGR levels were higher in the mRNA vaccine group than in the vector or mix-and-match vaccine groups at T2. The optimal cutoffs for RBD Ab and NAb, which were used to determine the presence of T cell responses, were 5.7 binding antibody units per milliliter (BAU mL-1) and 12.0 IU mL-1, respectively. Age, sex, and vaccine type affected the humoral and cellular immune responses, and T cell responses could be estimated from RBD Ab and NAb levels. IMPORTANCE There have been few studies that comprehensively evaluated factors affecting immune responses and the correlation between humoral and cellular immune responses after vector, mix-and-match, and mRNA vaccines against SARS-CoV-2. Therefore, we analyzed the effects of age, sex, and the different vaccine regimens on the immune responses to vaccination against SARS-CoV-2. The correlation between humoral and cellular immune responses and the cutoffs were derived for RBD antibodies and neutralizing antibodies to predict the presence of the cellular immune responses. In this comprehensive study, we demonstrated that there were differences in the immune responses induced after vaccination depending on the age and sex of an individual. Among the three vaccine regimens, the mix-and-match and mRNA vaccines induced the most robust immune responses. Finally, the proposed optimal cutoffs for RBD and neutralizing antibodies may be useful for predicting cellular immune responses when assays for cellular immune responses are not available.

Multifocal organoids reveal clonal associations between synchronous intestinal tumors with pervasive heterogeneous drug responses.

Multifocal colorectal cancer (CRC) comprises both clonally independent primary tumors caused by inherited predisposition and clonally related tumors mainly due to intraluminal spreading along an intact basement membrane. The distinction between these multifocal CRCs is essential because therapeutic strategies vary according to the clonal association of multiple tumor masses. Here, we report one unique case of synchronous intestinal cancer (SIC) with tumors occurring along the entire bowel tract, including the small intestine. We established six patient-derived organoids (PDOs), and patient-derived cell lines (PDCs) from each site of the SIC, which were subjected to extensive genomic, transcriptomic, and epigenomic sequencing. We also estimated the drug responses of each multifocal SIC to 25 clinically relevant therapeutic compounds to validate how the clinically actionable alternations between SICs were associated with drug sensitivity. Our data demonstrated distinct clonal associations across different organs, which were consistently supported by multi-omics analysis, as well as the accordant responses to various therapeutic compounds. Our results indicated the imminent drawback of a single tumor-based diagnosis of multifocal CRC and suggested the necessity of an in-depth molecular analysis of all tumor regions to avoid unexpected resistance to the currently available targeted therapies.

Deep learning-based quantitative analyses of spontaneous movements and their association with early neurological development in preterm infants.

This study aimed to develop quantitative assessments of spontaneous movements in high-risk preterm infants based on a deep learning algorithm. Video images of spontaneous movements were recorded in very preterm infants at the term-equivalent age. The Hammersmith Infant Neurological Examination (HINE) was performed in infants at 4 months of corrected age. Joint positional data were extracted using a pretrained pose-estimation model. Complexity and similarity indices of joint angle and angular velocity in terms of sample entropy and Pearson correlation coefficient were compared between the infants with HINE < 60 and ≥ 60. Video images of spontaneous movements were recorded in 65 preterm infants at term-equivalent age. Complexity indices of joint angles and angular velocities differed between the infants with HINE < 60 and ≥ 60 and correlated positively with HINE scores in most of the joints at the upper and lower extremities (p < 0.05). Similarity indices between each joint angle or joint angular velocity did not differ between the two groups in most of the joints at the upper and lower extremities. Quantitative assessments of spontaneous movements in preterm infants are feasible using a deep learning algorithm and sample entropy. The results indicated that complexity indices of joint movements at both the upper and lower extremities can be potential candidates for detecting developmental outcomes in preterm infants.

Lipid signatures reflect the function of the murine primary placentation†.

The placenta regulates maternal-fetal communication, and its defect leads to significant pregnancy complications. The maternal and embryonic circulations are primitively connected in early placentation, but the function of the placenta during this developmentally essential period is relatively unknown. We thus performed a comparative proteomic analysis of the placenta before and after primary placentation and found that the metabolism and transport of lipids were characteristically activated in this period. The placental fatty acid (FA) carriers in specific placental compartments were upregulated according to gestational age, and metabolomic analysis also showed that the placental transport of FAs increased in a time-dependent manner. Further analysis of two mutant mice models with embryonic lethality revealed that lipid-related signatures could reflect the functional state of the placenta. Our findings highlight the importance of the nutrient transport function of the primary placenta in the early gestational period and the role of lipids in embryonic development. SUMMARY SENTENCE: The placenta is activated characteristically in terms of lipid transport during primary placentation, and the lipid-related signatures closely reflect the functional state of the placenta.

Topoisomerase IIIß Deficiency Induces Neuro-Behavioral Changes and Brain Connectivity Alterations in Mice.

Topoisomerase IIIß (Top3ß), the only dual-activity topoisomerase in mammals that can change topology of both DNA and RNA, is known to be associated with neurodevelopment and mental dysfunction in humans. However, there is no report showing clear associations of Top3ß with neuropsychiatric phenotypes in mice. Here, we investigated the effect of Top3ß on neuro-behavior using newly generated Top3ß deficient (Top3ß-/-) mice. We found that Top3ß-/- mice showed decreased anxiety and depression-like behaviors. The lack of Top3ß was also associated with changes in circadian rhythm. In addition, a clear expression of Top3ß was demonstrated in the central nervous system of mice. Positron emission tomography/computed tomography (PET/CT) analysis revealed significantly altered connectivity between many brain regions in Top3ß-/- mice, including the connectivity between the olfactory bulb and the cerebellum, the connectivity between the amygdala and the olfactory bulb, and the connectivity between the globus pallidus and the optic nerve. These connectivity alterations in brain regions are known to be linked to neurodevelopmental as well as psychiatric and behavioral disorders in humans. Therefore, we conclude that Top3ß is essential for normal brain function and behavior in mice and that Top3ß could be an interesting target to study neuropsychiatric disorders in humans.

The Quantitative Trait Loci Mapping of Rice Plant and the Components of Its Extract Confirmed the Anti-Inflammatory and Platelet Aggregation Effects In Vitro and In Vivo.

Unpredictable climate change might cause serious lack of food in the world. Therefore, in the present world, it is urgent to prepare countermeasures to solve problems in terms of human survival. In this research, quantitative trait loci (QTLs) were analyzed when rice attacked by white backed planthopper (WBPH) were analyzed using 120 Cheongcheong/Nagdong double haploid lines. Moreover, from the detected QTLs, WBPH resistance-related genes were screened in large candidate genes. Among them, OsCM, a major gene in the synthesis of Cochlioquinone-9 (cq-9), was screened. OsCM has high homology with the sequence of chorismate mutase, and exists in various functional and structural forms in plants that produce aromatic amino acids. It also induces resistance to biotic stress through the synthesis of secondary metabolites in plants. The WBPH resistance was improved in rice overexpressed through map-based cloning of the WBPH resistance-related gene OsCM, which was finally detected by QTL mapping. In addition, cq-9 increased the survival rate of caecal ligation puncture (CLP)-surgery mice by 60%. Moreover, the aorta of rat treated with cq-9 was effective in vasodilation response and significantly reduced the aggregation of rat platelets induced by collagen treatment. A cq-9, which is strongly associated with resistance to WBPH in rice, is also associated with positive effect of CLP surgery mice survival rate, vasodilation, and significantly reduced rat platelet aggregation induced by collagen treatment. Therefore, cq-9 presents research possibilities as a substance in a new paradigm that can act on both Plant-Insect in response to the present unpredictable future.

Heart defects and embryonic lethality in Asb2 knock out mice correlate with placental defects.

Asb2, ankyrin repeat, and SOCS box protein 2 form an E3 ubiquitin ligase complex. Asb2 ubiquitin ligase activity drives the degradation of filamins, which have essential functions in humans. The placenta is a temporary organ that forms during pregnancy, and normal placentation is important for survival and growth of the fetus. Recent studies have shown that approximately 25-30% of knockout (KO) mice have non-viable offspring, and 68% of knockout lines exhibit placental dysmorphologies. There are very few studies on Asb2, with insufficient research on its role in placental development. Therefore, we generated Asb2 knockout mice and undertook to investigate Asb2 expression during organogenesis, and to identify its role in early embryonic and placental development. The external morphology of KO embryos revealed abnormal phenotypes including growth retardation, pericardial effusion, pale color, and especially heart beat defect from E 9.5. Furthermore, Asb2 expression was observed in the heart from E 9.5, indicating that it is specifically expressed during early heart formation, resulting in embryonic lethality. Histological analysis of E 10.5 KO heart showed malformations such as failure of chamber formation, reduction in trabeculated myocardium length, absence of mesenchymal cells, and destruction of myocardium wall. Moreover, the histological results of Asb2-deficient placenta showed abnormal phenotypes including small labyrinth and reduced vascular complexity, indicating that failure to establish mature circulatory pattern affects the embryonic development and results in early mortality. Collectively, our results demonstrate that Asb2 knockout mice have placental defects, that subsequently result in failure to form a normal cardiac septum, and thereby result in embryo mortality in utero at around E 9.5.

Thermosensitive gallic acid-conjugated hexanoyl glycol chitosan as a novel wound healing biomaterial.

In the present study, a novel synthetic tissue adhesive material capable of sealing wounds without the use of any crosslinking agent was developed by conjugating thermosensitive hexanoyl glycol chitosan (HGC) with gallic acid (GA). The degree of N-gallylation was manipulated to prepare GA-HGCs with different GA contents. GA-HGCs demonstrated thermosensitive sol-gel transition behavior and formed irreversible hydrogels upon natural oxidation of the pyrogallol moieties in GA, possibly leading to GA-HGC crosslinks through intra/intermolecular hydrogen bonding and chemical bonds. The GA-HGC hydrogels exhibited self-healing properties, high compressive strength, strong tissue adhesive strength and biodegradability that were adjustable according to the GA content. GA-HGCs also presented excellent biocompatibility and wound healing effects. The results of in vivo wound healing efficacy studies on GA-HGC hydrogels indicated that they significantly promote wound closure and tissue regeneration by upregulating growth factors and recruiting fibroblasts compared to the untreated control group.

Cytotoxic activity of bromodomain inhibitor NVS-CECR2-1 on human cancer cells.

Bromodomain (BRD), a protein module that recognizes acetylated lysine residues on histones and other proteins, has recently emerged as a promising therapeutic target for human diseases such as cancer. While most of the studies have been focused on inhibitors against BRDs of the bromo- and extra-terminal domain (BET) family proteins, non-BET family BRD inhibitors remain largely unexplored. Here, we investigated a potential anticancer activity of the recently developed non-BET family BRD inhibitor NVS-CECR2-1 that targets the cat eye syndrome chromosome region, candidate 2 (CECR2). We show that NVS-CECR2-1 inhibits chromatin binding of CECR2 BRD and displaces CECR2 from chromatin within cells. NVS-CECR2-1 exhibits cytotoxic activity against various human cancer cells, killing SW48 colon cancer cells in particular with a submicromolar half maximum inhibition value mainly by inducing apoptosis. The sensitivity of the cancer cells to NVS-CECR2-1 is reduced by CECR2 depletion, suggesting that NVS-CECR2-1 exerts its activity by targeting CECR2. Interestingly, our data show that NVS-CECR2-1 also kills cancer cells by CECR2-independent mechanism. This study reports for the first time the cancer cell cytotoxic activity for NVS-CECR2-1 and provides a possibility of this BRD inhibitor to be developed as an anticancer therapeutic agent.

Protection of Lycopene against Embryonic Anomalies and Yolk Sac Placental Vasculogenic Disorders Induced by Nicotine Exposure.

Identification of a new agent from natural products for the protection of embryonic anomalies is potentially valuable. To investigate the protective effect exerted by lycopene against nicotine-induced malformations, mouse embryos in embryonic day 8.5 with yolk sac placentas were cocultured with 1 mM nicotine and/or lycopene (1 × 10-6, 1 × 10-5 µM) for 48 h. The morphological defects and apoptotic cell deaths in the embryo and yolk sac placenta of the nicotine group were significantly increased. Exposure to nicotine resulted in reduced superoxide dismutase (SOD) activity and cytoplasmic SOD and cytoplasmic glutathione peroxidase mRNA levels, but increased lipid peroxidation level in embryos. Moreover, treatment with nicotine resulted in aggravated expressions of the mRNA or protein level of antiapoptotic (BCL2-associated X protein, B-cell lymphoma-extralarge, and caspase 3), anti-inflammatory (nuclear factor kappa-light-chain-enhancer of activated B cells and tumor necrosis factor-alpha), and vasculogenic (vascular endothelial growth factor-alpha, insulin-like growth factor-1, alpha smooth muscle actin, transforming growth factor-beta 1, and hypoxia inducible factor-1 alpha) factors in the embryo and yolk sac placenta. However, all the parameters were significantly improved by treatment with lycopene, as compared to the nicotine group. These findings indicate the potential of lycopene as a protective agent against embryonic anomalies and yolk sac vasculogenic and placenta-forming defects induced by nicotine through modulations of oxidative, apoptotic, vasculogenic, and inflammatory activities.

Effect of enzyme-assisted extraction on the physicochemical properties and bioactive potential of lotus leaf polysaccharides.

Lotus leaf polysaccharides were extracted by enzyme-assisted extraction using α-amylase (LLEP-A), cellulose (LLEP-C), pectinase (LLEP-P) or protease (LLEP-PR). Their physicochemical properties and immunostimulatory activities were compared with those of hot-water extracted polysaccharides (LLWP). HPAEC-PDA and HPSEC-RI profiles indicated that variations in their molecular weight patterns and chemical compositions. Moreover, their effects on proliferation, phagocytic activity, and cytokine production in macrophages could be ordered as LLEP-P > LLEP-C > LLEP-A > LLWP > LLEP-PR, suggesting that LLEP-P by pectinase-assisted extraction was the most potent enhancer of macrophage activation. LLEP-P was further purified by gel filtration, and the main fraction (LLEP-P-І) was obtained to elucidate the structural and functional properties. LLEP-P-І (14.63 × 103 g/mol) mainly consisted of rhamnose, arabinose, galactose, and galacturonic acid at molar percentages of 15.5:15.8:20.1:32.8. FT-IR spectra indicated the predominant acidic and esterified form, suggesting the pectic-like structure. Above all, LLEP-P-І exerted greater stimulation effects on NO and cytokines production and the phagocytic activity in macrophages. Transcriptome analysis also demonstrated that LLEP-P and LLEP-P-І could upregulate macrophage immune response genes, including cytokines, chemokines, and interferon via TLR and JAK-STAT signaling. Thus, these results suggest that pectinase application is most suitable to obtain immunostimulatory polysaccharides from lotus leaves.