Biological activity, limitations and steady-state delivery of functional substances for precision nutrition.

Food-related functional substances with biological activity serve as a crucial material foundation for achieving precision nutrition, which has gained increasing attraction in regulating physiological functions, preventing chronic diseases, and maintaining human health. Nutritional substances typically include bioactive proteins, peptides, polysaccharides, polyphenols, functional lipids, carotenoids, probiotics, vitamins, saponins, and terpenes. These functional substances play an essential role in precise nutrition. This chapter introduces and summarizes typical functional substances to demonstrate the challenges in precision nutrition for their stability, solubility, and bioavailability. The current status of delivery systems of functional substances is described to give an insight into the development of desirable characteristics, such as food grade status, high loading capacity, site targeting, and controlled release capacity. Finally, the applications of food-borne delivery systems of functional substances for precision nutrition are emphasized to meet the requirement for precision nutrition during nutritional intervention for chronic diseases.

Identification of Autophagy-Related Biomarkers and Diagnostic Model in Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease. Its accurate pathogenic mechanisms are incompletely clarified, and effective therapeutic treatments are still inadequate. Autophagy is closely associated with AD and plays multiple roles in eliminating harmful aggregated proteins and maintaining cell homeostasis. This study identified 1191 differentially expressed genes (DEGs) based on the GSE5281 dataset from the GEO database, intersected them with 325 autophagy-related genes from GeneCards, and screened 26 differentially expressed autophagy-related genes (DEAGs). Subsequently, GO and KEGG enrichment analysis was performed and indicated that these DEAGs were primarily involved in autophagy-lysosomal biological process. Further, eight hub genes were determined by PPI construction, and experimental validation was performed by qRT-PCR on a SH-SY5Y cell model. Finally, three hub genes (TFEB, TOMM20, GABARAPL1) were confirmed to have potential application for biomarkers. A multigenic prediction model with good predictability (AUC = 0.871) was constructed in GSE5281 and validated in the GSE132903 dataset. Hub gene-targeted miRNAs closely associated with AD were also retrieved through the miRDB and HDMM database, predicting potential therapeutic agents for AD. This study provides new insights into autophagy-related genes in brain tissues of AD patients and offers more candidate biomarkers for AD mechanistic research as well as clinical diagnosis.

Ginkgetin attenuates bone loss in OVX mice by inhibiting the NF-κB/IκBα signaling pathway.

Background: Osteoporosis is a disease associated with bone resorption, characterized primarily by the excessive activation of osteoclasts. Ginkgetin is a compound purified from natural ginkgo leaves which has various biological properties, including anti-inflammation, antioxidant, and anti-tumor effects. This study investigated the bone-protective effects of ginkgetin in ovariectomized (OVX) mice and explored their potential signaling pathway in inhibiting osteoclastogenesis in a mouse model of osteoporosis. Methods: Biochemical assays were performed to assess the levels of Ca, ALP, and P in the blood. Micro CT scanning was used to evaluate the impact of ginkgetin on bone loss in mice. RT-PCR was employed to detect the expression of osteoclast-related genes (ctsk, c-fos, trap) in their femoral tissue. Hematoxylin and eosin (H&E) staining was utilized to assess the histopathological changes in femoral tissue due to ginkgetin. The TRAP staining was used to evaluate the impact of ginkgetin osteoclast generation in vivo. Western blot analysis was conducted to investigate the effect of ginkgetin on the expression of p-NF-κB p65 and IκBα proteins in mice. Results: Our findings indicate that ginkgetin may increase the serum levels of ALP and P, while decreasing the serum level of Ca in OVX mice. H&E staining and micro CT scanning results suggest that ginkgetin can inhibit bone loss in OVX mice. The TRAP staining results showed ginkgetin suppresses the generation of osteoclasts in OVX mice. RT-PCR results demonstrate that ginkgetin downregulate the expression of osteoclast-related genes (ctsk, c-fos, trap) in the femoral tissue of mice, and this effect is dose-dependent. Western blot analysis results reveal that ginkgetin can inhibit the expression of p-NF-κB p65 and IκBα proteins in mice. Conclusion: Ginkgetin can impact osteoclast formation and activation in OVX mice by inhibiting the NF-κB/IκBα signaling pathway, thereby attenuating bone loss in mice.

Radiating blood flow signal: A new ultrasound feature of thyroid carcinoma.

OBJECTIVE: To summary radiating blood flow signals and evaluate their diagnostic value in differentiating benign and malignant thyroid nodules. MATERIALS AND METHODS: We retrospectively recruited consecutive patients undergoing US at 4 hospitals from 2018 to 2022. In a training dataset, the correlations of US features with malignant thyroid nodules were assessed by multivariate logistic analysis. Multivariate logistic regression models involving the ACR TI-RADS score, radiating blood flow signals and their combination were built and validated internally and externally. The AUC with 95% asymptotic normal confidence interval as well as sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) with 95% exact binomial confidence intervals were calculated. RESULTS: Among 2475 patients (1818 women, age: 42.47 ± 11.57; 657 men, age: 42.16 ± 11.69), there were 3187 nodules (2342 malignant nodules and 845 benign nodules). Radiating blood flow signals were an independent risk factor for diagnosing thyroid carcinoma. In the training set, the AUC of the model using the combination of radiating blood flow signals and the ACR TI-RADS score (0.95 95 % CI: [0.94, 0.97]; P < 0.001) was significantly higher than that of the ACR TI-RADS model (0.91 [0.89, 0.93]). In the two internal validation sets and the external validation set, the AUCs of the combination model were 0.97 [0.96, 0.98], 0.92 [0.88, 0.96], and 0.91 [0.86, 0.95], respectively, and were all significantly higher than that of the ACR TI-RADS score (0.92 [0.90, 0.95], 0.86 [0.81, 0.91], 0.84 [0.79, 0.89]; P < 0.001). CONCLUSION: Radiating blood flow is a new US feature of thyroid carcinomas that can significantly improve the diagnostic performance vs. the ACR TI-RADS score.

[Clinical observation of virtual reality technology combined with isokinetic strength training for patients after anterior cruciate ligament reconstruction].

OBJECTIVE: To explore application value and effectiveness of virtual reality technology combined with isokinetic muscle strength training in the rehabilitation of patients after anterior cruciate ligament (ACL) reconstruction surgery. METHODS: Forty patients who underwent ACL reconstruction surgery from December 2021 to January 2023 were selected and divided into control group and observation group according to treatment methods, 20 patients in each group. Control group was received routine rehabilitation training combined with isokinetic muscle strength training, including 15 males and 5 females, aged from 17 to 44 years old, with an average of (29.10±8.60) years old. Observation group was performed virtual reality technology combined with isokinetic muscle strength training, including 16 males and 4 females, aged from 17 to 45 years old with an average of (30.95±9.11) years old. Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque between two groups at 12 (before training) and 16 weeks (after training) after surgery were compared. RESULTS: All patients were followed up for 1 to 6 months with an average of (3.30±1.42) months. There were no statistically significant difference in Lysholm knee joint score, peak knee extension peak torque, and peak knee flexion peak torque between two groups (P>0.05) before training. After training, Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque of both groups were improved compared to before training (P<0.05);there were significant difference in Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque between two groups(P<0.05). CONCLUSION: The application of virtual reality technology combined with isokinetic muscle strength training could promote recovery of knee joint function and enhance muscle strength in patients after ACL reconstruction surgery in further.

Size-controllable food-grade nanoparticles based on sea cucumber polypeptide with good anti-oxidative capacity to prolong lifespan in tumor-bearing mice.

Liver cancer, a malignancy with a rising global incidence, poses a significant challenge in achieving effective treatment outcomes. As food-derived nutrient, sea cucumber peptide (SCP) has shown promising anticancer effects. Therefore, we explored the nanodelivery systems to encapsulate SCP to enhance its stability in the gastrointestinal tract and improve absorption within the tumor microenvironment. This study aimed to develop size-controllable multifunctional nanoparticles using SCP, procyanidins (PCs), and vanillin through molecular assembly via a one-pot Mannich condensation approach. These food-grade nanoparticles demonstrated water solubility and exhibited a spherical structure with sizes ranging from 441 to 1360 nm, depending on the concentration of the reactants. In vitro cell experiments demonstrated that SCP nanoparticles modified with PCs effectively reduced the generation of reactive oxygen species from H2O2 and acrylamide while maintaining normal levels of mitochondrial membrane potential. Furthermore, in vivo nutrition intervention studies conducted on tumor-bearing mice revealed that mice treated with SCP nanoparticles exhibited a survival rate of 40 %, which was significantly higher than the 0 % and 20 % survival rates observed in the control and SCP-treated groups, respectively. These findings suggest that SCP nanoparticles, possessing antioxidative properties and controllable sizes, hold potential for precision nutrition in the field of cancer treatment.

Addition of an affected family member to a previously ascertained autosomal recessive nonsyndromic hearing loss pedigree and systematic phenotype-genotype analysis of splice-site variants in MYO15A.

Pathogenic variants in MYO15A are known to cause autosomal recessive nonsyndromic hearing loss (ARNSHL), DFNB3. We have previously reported on one ARNSHL family including two affected siblings and identified MYO15A c.5964+3G > A and c.8375 T > C (p.Val2792Ala) as the possible deafness-causing variants. Eight year follow up identified one new affected individual in this family, who also showed congenital, severe to profound sensorineural hearing loss. By whole exome sequencing, we identified a new splice-site variant c.5531+1G > C (maternal allele), in a compound heterozygote with previously identified missense variant c.8375 T > C (p.Val2792Ala) (paternal allele) in MYO15A as the disease-causing variants. The new affected individual underwent unilateral cochlear implantation at the age of 1 year, and 5 year follow-up showed satisfactory speech and language outcomes. Our results further indicate that MYO15A-associated hearing loss is good candidates for cochlear implantation, which is in accordance with previous report. In light of our findings and review of the literatures, 58 splice-site variants in MYO15A are correlated with a severe deafness phenotype, composed of 46 canonical splice-site variants and 12 non-canonical splice-site variants.

Water-soluble iron in PM2.5 in winter over six Chinese megacities: Distributions, sources, and environmental implications.

Water-soluble iron (ws-Fe) in PM2.5 plays a crucial role in biogeochemical cycles and atmospheric chemical processes. The anthropogenic sources of ws-Fe have attracted considerable attention owing to its high solubility. However, few studies have investigated the content of PM2.5 ws-Fe in the urban environment. In the present study, we characterized the spatial distributions of ws-Fe in six Chinese megacities in the winter of 2019. Furthermore, we investigated the speciation of PM2.5 ws-Fe (ws-Fe(II) and ws-Fe(III)), potential sources of ws-Fe, and association between ws-Fe and particle-bound reactive oxygen species (ROS). Higher ws-Fe concentrations were observed in northern cities (Harbin, Beijing, and Xi'an) than in southern cities (Chengdu, Wuhan, and Guangzhou). Moreover, atmospheric ws-Fe concentrations in urban China were several folds higher than those in urban areas of the United States and several orders of magnitude higher than those in remote oceans, indicating that China is a key contributor to global atmospheric ws-Fe. The dominant form of ws-Fe was ws-Fe(III) in Beijing, whereas ws-Fe(II) was more abundant in the other five cities. The concentrations of ws-Fe and ws-Fe(II) concentrations increased with increasing PM2.5 levels in all the six cities, however, we did not observe any consistent pattern of ws-Fe(III) concentration. Biomass burning was a dominant source of ws-Fe in all cities except Beijing. A strong positive correlation was observed between particle-bound ROS content and ws-Fe; this finding is consistent with those of previous studies indicating that ws-Fe in PM2.5 notably influences atmospheric chemical processes and human health.

A comprehensive evaluation of PM2.5-bound PAHs and their derivative in winter from six megacities in China: Insight the source-dependent health risk and secondary reactions.

Atmospheric PAHs (polycyclic aromatic hydrocarbons) and their derivatives are a global concern that influences environments and threatens human health. Concentrations of 52 PAHs and the main derivatives in six Chinese megacities were measured in the winter of 2019. The concentrations of ∑PAHs (sum of 52 PAHs) ranged from 19.42 ± 7.68 to 65.40 ± 29.84 ng m-3, with significantly higher levels in northern cities (Harbin [HB], Beijing [BJ], and Xi'an [XA]) than southern ones (Wuhan [WH], Chengdu [CD] and Guangzhou [GZ]). Source apportionment of ∑PAHs was conducted by the PMF model and results showed coal combustion and traffic emissions were the two dominant sources, which dominated ∑PAHs in northern and southern cities, respectively. Biomass burning was also characterized as a crucial source of ∑PAHs and showed extremely high contributions in XA (42.5%). Assisted by the individual PAH source apportionment results, the source-depend TEQ (total BaP equivalent) and incremental lifetime cancer risk (ILCR) were firstly reported in these cities. The results highlighted the contributions of coal combustion and biomass burning to both TEQ and ILCR, which were underestimated by ∑PAHs source apportionment. Secondary organic aerosol-derived PAHs were demonstrated to increase the TEQ compared with the fresh PAHs and three parameters, namely temperature, relative humidity, and O3 concentrations were characterized by multiple linear regression as the principal factors influencing secondary reactions of PAHs in winter. This study provides accurate human health-orientated results and potential control measures to mitigate the toxicity of secondary formed PAHs, and significantly decrease the uncertainty level of traditional methods. The results also revealed great progress in air pollution control by the Chinese government in the past 20 years, but still a long way to go to formulate strict emission control strategies from both environmental and human health-protective perspectives.

Analysis of the genotype-phenotype correlation of MYO15A variants in Chinese non-syndromic hearing loss patients.

BACKGROUND: Mutations in the MYO15A gene are a widely recognized cause of autosomal recessive non-syndromic sensorineural hearing loss (NSHL) globally. Here, we examined the role and the genotype-phenotype correlation of MYO15A variants in a cohort of Chinese NSHL cases. METHODS: Eighty-one cases with evidenced MYO15A variants from the 2263 Chinese NSHL cases, who underwent next-generation sequencing (NGS), were enrolled in the study. We investigated the association of MYO15A variants with the severity, progression and age of onset of hearing loss, as well as compared it to the previous reports in different nationalities. The cases were divided into groups according to the number of truncating variants: 2 truncating, 1 truncating and 1 non-truncating, 2 non-truncating variants, and compared the severity of HL among the groups. RESULTS: MYO15A accounted for 3.58% (81/2263) of all NSHL cases. We analyzed 81 MYO15A-related NSHL cases, 73 of whom were with congenital bilateral, symmetric or severe-to-profound hearing loss (HL), however, 2 of them had a postlingual, asymmetric, mild or moderate HL. There were 102 variants identified in all MYO15A structural domains, 76.47% (78/102) of whom were novel. The most common types of detected variants were missense (44/102, 43.14%), followed by frameshift (27/102, 26.47%), nonsense (14/102, 13.72%), splice site (10/102, 9.80%), in frame (4/102, 3.92%), non-coding (2/102, 1.96%) and synonymous (1/102, 0.98%). The most recurrent variant c.10245_10247delCTC was detected in 12 cases. We observed that the MYO15A variants, located in its N-terminal, motor and FERM domains, led to partial deafness with better residual hearing at low frequencies. There were 34 cases with biallelic truncating variants, 37 cases with monoallelic truncating variants, and 13 cases with biallelic non-truncating variants. The biallelic non-truncating variants group had the least number of cases (12/81), and most of them (10/12) were with profound NSHL. CONCLUSIONS: MYO15A is a major gene responsible for NSHL in China. Cases with MYO15A variants mostly showed early-onset, symmetric, severe-to-profound hearing loss. This study is by far the largest focused on the evaluation of the genotype-phenotype correlations among the variants in the MYO15A gene and its implication in the outcome of NSHL. The biallelic non-truncating MYO15A variants commonly caused profound HL, and the cases with one or two truncating MYO15A variants tended to increase the risk of HL. Nevertheless, further investigations are needed to clarify the causes for the variable severities and progression rates of hearing loss and the detected MYO15A variants in these cases.

Inhibition of p38 MAPK increases the sensitivity of 5-fluorouracil-resistant SW480 human colon cancer cells to noscapine.

A major cause of treatment failure in advanced colon cancer is resistance to chemotherapy. p38 mitogen-activated protein kinase (MAPK) has been associated with cellular apoptosis and plays an important role in multidrug resistance (MDR) in cancer cells. In the present study the effect of p38 MAPK on the sensitivity of 5-fluorouracil (5-FU)-resistant SW480 (SW480/5-FU) human colon cancer cells to noscapine was investigated. Following p38 MAPK interference, the inhibitory effect of noscapine on cell viability and proliferation was increased in the SW480/5-FU cells and there was also a decrease in the expression level of minichromosome maintenance proteins, recombinant Ki-67 and proliferating cell nuclear antigen. Inhibition of p38 MAPK also enhanced noscapine-induced G1-phase cell cycle arrest in the SW480/5-FU cells and there was also a decrease in the protein and mRNA expression level of cyclin D, cyclin E and cyclin-dependent kinase 2, and an increase in the expression level of P57. Furthermore, p38 MAPK interference increased noscapine-induced apoptosis of the SW480/5-FU cells and there was an increase in the protein and mRNA expression level of caspases-3 and 8 and Bax, and decreased Bcl-2 expression level. The sensitivity of the SW480/5-FU cells to noscapine was also increased following p38 MAPK interference, as demonstrated by MDR inhibition via decreased Akt activity and reduced protein expression level of the MDR proteins P-glycoprotein, multidrug resistance protein 1 and ATP-binding cassette G2. These observations indicated that inhibition of p38 MAPK increased the sensitivity of the SW480/5-FU cells to noscapine by suppressing proliferation, induction of cell cycle arrest and apoptosis, and reversal of MDR in the SW480/5-FU cells.

Variant analysis of 92 Chinese Han families with hearing loss.

BACKGROUND: Hearing loss (HL) is the most frequent sensory deficit in humans, HL has strong genetic heterogeneity. The genetic diagnosis of HL is very important to aid treatment decisions and to provide prognostic information and genetic counseling for the patient's family. METHODS: We undertook pedigree analysis in 92 Chinese non-syndromic HL patients by targeted next-generation sequencing and Sanger sequencing. RESULTS: Among the 92 HL patients, 18 were assigned a molecular diagnosis with 33 different variants in 14 deafness genes. Eighteen of the variants in 12 deafness genes were novel. Variants in TMC1, CDH23, LOXHD1 and USH2A were each detected in two probands, and variants in POU3F4, OTOA, GPR98, GJB6, TRIOBP, SLC26A4, MYO15A, TNC, STRC and TMPRSS3 were each detected in one proband. CONCLUSION: Our findings expand the spectrum of deafness gene variation, which will inform genetic diagnosis of deafness and add to the theoretical basis for the prevention of deafness.

Transcriptome analysis of the early stage ifnlr1-mutant zebrafish indicates the immune response to auditory dysfunction.

BACKGROUND: IFNLR1 has been recently identified to be related to autosomal dominant nonsyndromic sensorineural hearing loss (ADNSHL). It is reported to be expressed in the inner ear of mice and the lateral line of zebrafish. However, it remains unclear how defects in this gene lead to hearing loss. OBJECTIVES: To elucidate the global gene expression changes in zebrafish when the expression of ifnlr1 is downregulated. METHODS: Transcriptome analysis was performed on ifnlr1 morpholino knockdown zebrafish and the control zebrafish using RNA-seq technology. RESULTS: The results show that 262 differentially expressed genes (DEGs) were up-regulated while 146 DEGs were down-regulated in the E4I4-Mo zebrafish larvae compared to the control-Mo. Six pathways were significantly enriched, including steroid biosynthesis pathway, adipocytokine signaling pathway, cytokine-cytokine receptor interaction pathway, p53 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and terpenoid backbone biosynthesis pathway. Among them, three pathways (steroid biosynthesis pathway, cytokine-cytokine receptor interaction pathway and p53 signaling pathway) are immune-associated. CONCLUSIONS: The transcriptome analysis results contribute to the groundwork for future research on the pathogenesis of IFNLR1-associated hearing loss.

The quality and antioxidant elucidation of germinated flaxseed treated with acidic electrolyzed water.

The endogenous fortification of antioxidant lipid concomitants in flaxseed was imperative to improve the oxidative stability of α-linolenic acid (ALA) in flaxseed and flaxseed oil upon processing, storage and gastrointestinal digestion. The comparative effects of acidic electrolyzed water (ACEW) and tap water (TW) on the triglyceride configuration, typical lipid concomitants, and antioxidant properties of flaxseed were conducted during 0-5 days of germination. The results showed that ACEW enhanced the germination rate of flaxseed by 18.25% and simultaneously suppressed the dynamic depletion of ALA by 5.32% when compared with TW (p < .05). The total phenolic acids, lignans, and flavonoids were effectively accumulated in flaxseed following ACEW-mediated germination with the further increase by 4.82%, 15.48%, and 8.22% in comparison with those induced by TW (p < .05). The total contents of cyclolinopeptides in flaxseed progressively dropped following either ACEW or TW treatment, a slighter decrease by 5.59% for flaxseed treated by ACEW than that by TW. Notably, the maximum accumulation of tocopherols and phytosterols had been early obtained for flaxseed treated with ACEW for 2-3 days due to the de novo synthesis or intermolecular conformational transition (p < .05). Most importantly, ACEW-mediated germination led to higher increment of the thermal oxidative stability and antioxidant properties of flaxseed and flaxseed oil in comparison to TW. In brief, the initial oxidation temperature increased by 7.09% and 3.06% (p < .05), and the antioxidant activities as evaluated by DPPH, ABTS, and FRAP values raised by 3.86%-28.07% and 4.21%-9.18% (p < .05), respectively. These findings clarify that the germination especailly mediated by ACEW could be an effective method to further optimize the nutritional and functional properties of flaxseed through reconstructing the endogenous antioxidant system.

Clinical efficacy of duodenoscopy combined with laparoscopy in the treatment of patients with severe acute pancreatitis and pancreatic pseudocyst, and the effects on IL-6 and CRP.

The study aimed to investigate the clinical efficacy of duodenoscopy combined with laparoscopy in the treatment of patients with severe acute pancreatitis (SAP) and pancreatic pseudocyst (PP), and its effects on serum inflammatory factors. Altogether 94 patients complicated with SAP and PP who were admitted to Weifang People's Hospital (Weifang, China) from September 2015 to December 2018 were included. Based on the different operation methods, 49 patients who underwent traditional laparotomy under laparoscopic surgery were included in group A, and 45 patients who underwent duodenoscopy and laparoscopy under duodenoscope to treat the drainage of nipple and pancreatic pseudocysts were included in group B. The expression levels of related serum indexes and serum stress indexes before and at 48 h after surgery, the postoperative nausea, vomiting and abdominal pain scores, as well as the clinical efficacy, perioperative related indexes, recovery and complications were compared between the two groups. The prognostic factors in both groups were assessed via Logistic univariate and multivariate analyses. C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-ß (IL-ß), endotoxin and nuclear factor κB (NF-κB) were significantly lower in group B than those in group A (P<0.001). Upregulating cortisol and norepinephrine in group B was lower than that in group A (P<0.001). The total effective rate in group B was higher than that in group A (P<0.05). The perioperative related indexes, recovery, and postoperative complications in group B were better than those in group A (P<0.05). Scores of abdominal pain, nausea and vomiting in group B were markedly lower than those in group A (P<0.001). Multivariate Logistic regression analysis showed that CRP, TNF-α, IL-6, IL-ß and surgical methods were independent risk factors for the prognosis of patients with SAP and PP. In conclusion, the combined treatment with duodenoscopy and laparoscopic surgery has little inflammatory and stress reaction, and it is highly safe, worthy to be popularized.

MiR-331-3p Links to Drug Resistance of Pancreatic Cancer Cells by Activating WNT/ß-Catenin Signal via ST7L.

BACKGROUND: Pancreatic cancer is an aggressive type of cancer with poor prognosis, short survival rate, and high mortality. Drug resistance is a major cause of treatment failure in the disease. MiR-331-3p has been reported to play an important role in several cancers. We previously showed that miR-331-3p is upregulated in pancreatic cancer and promotes pancreatic cancer cell proliferation and epithelial-to-mesenchymal transition-mediated metastasis by targeting ST7L. However, it is uncertain whether miR-331-3p is involved in drug resistance. METHODS: We investigated the relationship between miR-331-3p and pancreatic cancer drug resistance. As part of this, microRNA mimics or inhibitors were transfected into pancreatic cancer cells. Quantitative polymerase chain reaction was used to detect miR-331-3p expression, and flow cytometry was used to detect cell apoptosis. The Cell Counting Kit-8 assay was used to measure the IC50 values of gemcitabine in pancreatic cancer cells. The expression of multidrug resistance protein 1, multidrug resistance-related protein 1, breast cancer resistance protein, ß-Catenin, c-Myc, Cyclin D1, Bcl-2, and Caspase-3 was evaluated by Western blotting. RESULTS: We confirmed that miR-331-3p is upregulated in gemcitabine-treated pancreatic cancer cells and plasma from chemotherapy patients. We also confirmed that miR-331-3p inhibition decreased drug resistance by regulating cell apoptosis and multidrug resistance protein 1, multidrug resistance-related protein 1, and breast cancer resistance protein expression in pancreatic cancer cells, whereas miR-331-3p overexpression had the opposite effect. We further demonstrated that miR-331-3p effects in drug resistance were partially reversed by ST7L overexpression. In addition, overexpression of miR-331-3p activated Wnt/ß-catenin signaling in pancreatic cancer cells, and ST7L overexpression restored activation of Wnt/ß-catenin signaling. CONCLUSIONS: Taken together, our data demonstrate that miR-331-3p contributes to drug resistance by activating Wnt/ß-catenin signaling via ST7L in pancreatic cancer cells. These data provide a theoretical basis for new targeted therapies in the future.

Noscapine Induces Apoptosis in Human Colon Cancer Cells by Regulating Mitochondrial Damage and Warburg Effect via PTEN/PI3K/mTOR Signaling Pathway.

BACKGROUND: Noscapine is an opium alkaloid that has recently been shown to potentiate anti-cancer therapeutic effects by inducing apoptosis in various malignant cells without any detectable toxicity. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. MATERIALS AND METHODS: In this study, we explored the anti-cancer activity of noscapine in 5-fluorouracil (5-FU)-resistant human colon cancer cell lines HT29/5-FU and LoVo/5-FU and investigated the possible underlying mechanism. The apoptosis and mitochondrial morphology of cells were detected by TUNEL assay and transmission electron microscopy (TEM). The mitochondrial membrane potential (MMP) was determined using JC-1. The mitochondrial permeability transition pore (mPTP) opening was detected by the calcein-AM/cobalt assay. The levels of glucose, lactic, and ATP in cells were evaluated by ELISA kits. Relative protein expression levels were detected by Western blot. RESULTS: We verified that PTEN was involved in noscapine-induced apoptosis in HT29/5-FU and LoVo/5-FU cells. Noscapine greatly increased mitochondrial damage by altering mitochondrial morphology, inducing mitochondrial membrane potential depolarization, and enabling mitochondrial permeability transition pore opening in HT29/5-FU and LoVo/5-FU cells. In addition, noscapine inhibited the Warburg effect by decreasing the levels of glucose, lactic acid, and ATP and inhibiting the protein expression of glucose transporter 1, lactate dehydrogenase-B, hexokinase 2, and pyruvate kinase M2 in HT29/5-FU and LoVo/5-FU cells. However, PTEN interference counteracted the effect of noscapine on mitochondrial damage and the Warburg effect in HT29/5-FU and LoVo/5-FU cells by decreasing the activation of PI3K/mTOR signaling. CONCLUSION: These results indicated that noscapine induced the apoptosis of HT29/5-FU and LoVo/5-FU human colon cancer cells by regulating mitochondria damage and the Warburg effect via PTEN, and the process is closely related to the PI3K/mTOR signaling pathway.

Long noncoding RNA OSER1­AS1 promotes the malignant properties of non­small cell lung cancer by sponging microRNA­433­3p and thereby increasing Smad2 expression.

OSER1 antisense RNA 1 (OSER1­AS1), a long noncoding RNA, has been well studied in the context of hepatocellular carcinoma. However, its expression status, specific functions, and tumorigenic mechanism in non­small cell lung cancer (NSCLC) remain uninvestigated. Hence, this study aimed to assess OSER1­AS1 expression, test the malignancy­related biological functions of OSER1­AS1, and illustrate how they affect NSCLC progression. OSER1­AS1 expression in NSCLC was measured by reverse transcription­quantitative polymerase chain reaction. Cell Counting Kit­8 assay, flow cytometry, cell migration and invasion assay, and tumor xenograft assay were performed to analyze the effects of OSER1­AS1 on the malignant phenotypes of NSCLC cells. Bioinformatics prediction with luciferase reporter and RNA immunoprecipitation assays were performed to determine the interaction between OSER1­AS1 and microRNA­433­3p (miR­433­3p). OSER1­AS1 was strongly expressed in NSCLC tissues and cell lines. Enhanced OSER1­AS1 expression was significantly correlated with tumor size, TNM stage, and lymph node metastasis in patients with NSCLC. Patients with NSCLC exhibiting high OSER1­AS1 expression had shorter overall survival than those exhibiting low OSER1­AS1 expression. Functionally, a reduction in OSER1­AS1 expression led to significant decreases in NSCLC cell proliferation, migration, and invasion as well as an increase in cell apoptosis in vivo. OSER1­AS1 knockdown suppressed the tumorigenic ability of NSCLC cells in vivo. Mechanistically, OSER1­AS1 acts as a competing endogenous RNA (ceRNA) in NSCLC cells by sponging miR­433­3p and thereby increasing the expression of mothers against decapentaplegic homolog 2 (Smad2). Finally, restoration experiments revealed that the suppression of miR­433­3p and restoration of Smad2 both counteracted the suppressive effects of OSER1­AS1 depletion in NSCLC cells. Our findings illustrate the biological importance of the OSER1­AS1/miR­433­3p/Smad2 pathway in NSCLC progression and offer a novel perspective regarding the identification of effective therapeutic and diagnostic targets.

Effects of atmospheric pressure plasma jet on the physicochemical, functional, and antioxidant properties of flaxseed protein.

The aim of this study was to explore the effect of atmospheric pressure plasma jet (APPJ) on the physicochemical, functional, and antioxidant properties of flaxseed protein following APPJ treatment (0 to 240 s). The results showed that the pH value continuously dropped with the minimum value of 3.45 ± 0.15 after 240 s of APPJ treatment (-61.7%, P < 0.05). The relative protein solubility significantly declined after 15 s of APPJ treatment (-43.1%, P < 0.05), which was accompanied by the evident increase in mean particle size of flaxseed protein in aqueous solution (+157%, P < 0.05). Moreover, the surface hydrophobicity and contents of disulfide bonds gradually raised when the APPJ exposure time extended from 30 to 240 s. Notably, the foaming, emulsifying, and in vitro antioxidant properties of flaxseed protein were significantly improved following short time of APPJ treatment (5 to 15 s), which was paralleled with the changes of spatial conformation, mild protein oxidation, as well as the release of phenolic acids and flavonoids from naturally occurring protein-phenolic complex. Our findings elucidated that APPJ may be considered as an effective strategy to improve the functionality and antioxidant activities of flaxseed protein. PRACTICAL APPLICATION: We had evaluated the effect of APPJ treatment on the physicochemical, functional, and antioxidant properties of flaxseed protein, which was conducive to tailor flaxseed protein with the optimal techno-functionality and antioxidant activities as a potential nano-delivery vehicle.

Detecting novel mutations and combined Klinefelter syndrome in Usher syndrome cases.

BACKGROUND: Usher syndrome (USH) is an autosomal recessive disease characterized by hearing loss, vision loss, and occasionally vestibular dysfunction. Klinefelter syndrome (KS) is an X chromosome polyploidy characterized by one or more additional X chromosomes in males. To date, there has been no report of USH combined with KS. OBJECTIVES: This study examined the causative genes in three Chinese probands with congenital hearing loss. MATERIAL AND METHODS: Targeted next-generation sequencing (NGS) was performed to identify mutations in three probands with hearing loss. Low-coverage whole-genome sequencing (WGS) analysis of aneuploidy was used to verify the chromosome aneuploidy. RESULTS: Four novel MYO7A mutations were identified in two USH1 probands who were initially diagnosed with nonsyndromic hearing loss until the onset of vision loss. Another case was initially diagnosed with nonsyndromic hearing loss and USH2 and KS were discovered incidentally after the genetic analysis. CONCLUSIONS: Our findings expand the mutation spectrum of MYO7A. This is also the first report of concomitant USH and KS. Genetic testing can help with clinical management, particularly if an unrecognized syndromic disorder is identified before the onset of additional symptoms. A clinical genetic evaluation is recommended as part of the diagnostic work-up in congenital hearing loss.