Herein,a one-pot chemical reduction method was reported to prepare folic acid(FA)-stabilized silver nanoclusters(FA@Ag NCs),in which FA,hydrazine hydrate,and silver nitrate were used as capping agent,reducing agent,an...Herein,a one-pot chemical reduction method was reported to prepare folic acid(FA)-stabilized silver nanoclusters(FA@Ag NCs),in which FA,hydrazine hydrate,and silver nitrate were used as capping agent,reducing agent,and precursor,respectively.Several technologies were employed to investigate the structures and optical properties of FA@Ag NCs,including transmission electron microscopy(TEM),X-ray photoelectron spectrometer(XPS),Fourier transform infrared spectrometer(FTIR),X-ray diffractometer(XRD),fluorescence spectrometer,and ultraviolet visible absorption spectrometer.FA@Ag NCs were suggested to be highly dispersed and spherical with a size of around 2.8 nm.Moreover,the maximum excitation and emission wavelengths of FA@Ag NCs were 370 and 447 nm,respectively.Under the optimal detection conditions,FA@Ag NCs could be used to effectively detect malachite green with the linear detection range of 0.5-200μmol·L^(-1).The detection limit was 0.084μmol·L^(-1).The fluorescence-quenching mechanism was ascribed to the static quenching.The detection system based on FA@AgNCs was successfully used for the detection of malachite green in actual samples with good accuracy and reproducibility.展开更多
As PEGylated liposomes have witnessed remarkable advancements in drug delivery,their immunogenicity has emerged as a notable challenge.In this study,we discovered that a simple pre-injection of folic acid(FA)effective...As PEGylated liposomes have witnessed remarkable advancements in drug delivery,their immunogenicity has emerged as a notable challenge.In this study,we discovered that a simple pre-injection of folic acid(FA)effectively mitigated the immunogenicity of PEGylated liposomes and enhanced their in vivo performance by tolerating splenic marginal zone B cells.FA specifically inhibited the internalization of PEGylated liposomes by splenic marginal zone B cells,thereby reducing splenic lymphocyte proliferation and specific IgM secretion.This modulation alleviated Ig M-mediated accelerated blood clearance and adverse accumulation of the PEGylated liposomes in the skin.These findings provide new insights into the immunomodulatory effects of FA and promising avenues to enhance the efficacy and safety of PEGylated liposomal nanomedicines.展开更多
Preterm birth and suboptimal fetal growth remain significant perinatal challenges worldwide.Recent data indicate that China's perinatal profile has improved due to reductions in preterm birth rates.However,the cou...Preterm birth and suboptimal fetal growth remain significant perinatal challenges worldwide.Recent data indicate that China's perinatal profile has improved due to reductions in preterm birth rates.However,the country has a 6.5%prevalence of small-for-gestational-age(SGA),ranking fifth globally in total SGA birth numbers^([1,2]).展开更多
Tributyltin(TBT),a common organotin environmental pollutant,may pose a threat to human development during critical early-life periods.We aimed to assess the neurodevelopmental intergenerational toxicity of early-life ...Tributyltin(TBT),a common organotin environmental pollutant,may pose a threat to human development during critical early-life periods.We aimed to assess the neurodevelopmental intergenerational toxicity of early-life exposure to TBT and the protective effect of DNA methyl donor folic acid(FA).Specifically,after early-life exposure(1–21 days postfertilization,dpf)to TBT(0,1,10 and 100 ng/L),zebrafish(Danio rerio)were cultured in clean medium until sexual maturity.The exposed females were mated with unexposed males to produce embryos(F1).The F1 generation were cultured(4–120 hours post-fertilization,hpf)with and without 1 mmol/L FA.The neurotoxic effects of early-life TBT exposure for zebrafish and their offspring(F1)were significantly enhanced anxiety and reduced aggression,decreased gene expression of DNA methyltransferase in the brain and increased serotonin levels in the body.Moreover,the intergenerational neurodevelopmental toxicity,as manifested in the F1 generation,was attenuated by FA supplementation.In summary,early-life TBT exposure led to intergenerational neurodevelopmental deficits in zebrafish,and DNA methyl donors had a protective effect on F1 neurodevelopment,which can inform the prevention and treatment of intergenerational neurotoxicity due to organotin pollutants.展开更多
Oral squamous cell carcinoma(OSCC)is known as one of the most malignant tumors with high recurrence and fatality rate.The poor tumor-targeting ability of traditional chemotherapeutic drugs has been a grand challenge f...Oral squamous cell carcinoma(OSCC)is known as one of the most malignant tumors with high recurrence and fatality rate.The poor tumor-targeting ability of traditional chemotherapeutic drugs has been a grand challenge for anti-OSCC therapy.Beyond that,a large quantity of tumor associated macrophages in OSCC tissues further diminish the anti-tumor effects of these drugs.Therefore,we produced a therapeutic nano drug delivery system(FA-PEG-PLA-JQ1)through encapsulating JQ1[a small-molecule inhibitor of bromodomain containing protein 4(BRD4)]into the folic acid(FA)-modified nanoparticle(PEG-PLA),which could prolong the half-life of JQ1 and target the tumor tissues.And then,JQ1 released from this nanoparticle could prevent OSCC growth inducing tumor cell apoptosis,inhibiting tumor angiogenesis and the polarization of M2 type macrophages.In conclusion,our date demonstrated the therapeutic benefits of FA-PEG-PLA-JQ1 against OSCC in vivo or in vitro,which could be a novel treatment strategy for OSCC in coming days.展开更多
The study focuses on the development of biocompatible and stable FA-functionalized nanocrystalline cellulose(NCC)as a potential drug delivery system for targeting folate receptor-positive cancer cells.The FA-functiona...The study focuses on the development of biocompatible and stable FA-functionalized nanocrystalline cellulose(NCC)as a potential drug delivery system for targeting folate receptor-positive cancer cells.The FA-functionalized NCCs were synthesized through a series of chemical reactions,resulting in nanoparticles with favorable properties for biomedical applications.The microstructural analysis revealed that the functionalized NCCs maintained their rod-shaped morphology and displayed hydrodynamic diameters suitable for evading the mononuclear phagocytic system while being large enough to target tumor tissues.Importantly,these nanoparticles possessed a negative surface charge,enhancing their stability and repelling potential aggregation.The binding specificity of FA-functionalized NCCs to folate receptor-positive cancer cells was demonstrated through various assays.The free folic acid inhibition assay showed approximately 30%decrease in the binding of functionalized NCCs in the presence of just 5 mM free FA,confirming their selectivity for folate receptor-positive cells.Confocal microscopy further validated this specificity,as only cancer cells displayed significant binding of functionalized NCCs.Crucially,biocompatibility tests revealed that both NCCs and FA-functionalized NCCs had minimal effects on red blood cells,and they did not induce erythrocyte aggregation.Furthermore,cell viability assays demonstrated functionalized NCCs have selective cytotoxicity against colorectal cancer cells HT-29 and SW-620(68%–88%cell viability)while sparing noncancerous colon cells CCD-18Co(81%–97%cell viability).In summary,FA-functionalized NCCs exhibit promising characteristics for targeted drug delivery in cancer therapy.Their biocompatibility,stability,and selective cytotoxicity make them an attractive option for delivering therapeutic agents to folate receptor-positive cancer cells,potentially improving the effectiveness of cancer treatments while minimizing harm to healthy tissues.展开更多
Folic acid participates in the metabolism of homocysteine and lowers plasma homocysteine levels directly or indirectly. To establish a hyperhomocysteinemic pregnant rat model, 2 mL of DL-homocysteine was administered ...Folic acid participates in the metabolism of homocysteine and lowers plasma homocysteine levels directly or indirectly. To establish a hyperhomocysteinemic pregnant rat model, 2 mL of DL-homocysteine was administered daily by intraperitoneal injection at a dose of 200 mg/kg from day 10 to day 19 of gestation. Folic acid was administered by intragastric administration at a dose of 20 mg/kg during the period of preeclampsia induction. Results showed that systolic blood pressure, proteinuria/creatinine ratio, and plasma homocysteine levels in the hyperhomocysteinemic pregnant rats increased significantly, and that body weight and brain weight of rat pups significantly decreased. Folic acid supplementation markedly reversed the above-mentioned abnormal changes of hyperhomocysteinemic pregnant rats and rat pups. These findings suggest that folic acid can alleviate the symptoms of hyperhomocysteinemia- induced preeclampsia in pregnant rats without influencing brain development of rat pups.展开更多
AIM: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions. METHODS: Thirty-eight patients, with premalignant gastric lesions incl...AIM: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions. METHODS: Thirty-eight patients, with premalignant gastric lesions including 18 colonic-type intestinal metaplasia (IM) and 20 mild or moderate dysplasia, were randomly divided into a treatment group (n = 19) receiving folic acid 10 mg thrice daily and a control group (n = 19) receiving sucralfate 1 000 mg thrice daily for 3 mo. All patients underwent endoscopies and four biopsies were taken prior to treatment and repeated after concluding therapy. Folate concentrations in gastric mucosa were measured with chemiluminescent enzyme immunoassay. Epithelial apoptosis and the expression of Bcl-2 and p53 protein in gastric mucosa were detected with flow cytometric assay. RESULTS: The mean of folate concentration in gastric mucosa was 9.03±3.37 μg/g wet wt in the folic acid treatment group, which was significantly higher than 6.83±3.02 μg/g wet wt in the control group. Both the epithelial apoptosis rate and the tumor suppressor p53 expression in gastric mucosa significantly increased after folic acid treatment. In contrast, the expression of Bcl-2 oncogene protein decreased after folic acid therapy. CONCLUSION: These data indicate that folic acid may play an important role in the chemoprevention of gastric carcinogenesis by enhancing gastric epithelial apoptosis in the patients with premalignant lesions.展开更多
BACKGROUND： Folic acid is essential for normal functioning of the nervous system. Previous studies have focused on the effects of folic acid on astrocyte proliferation. OBJECTIVE： To explore the effects of folic aci...BACKGROUND： Folic acid is essential for normal functioning of the nervous system. Previous studies have focused on the effects of folic acid on astrocyte proliferation. OBJECTIVE： To explore the effects of folic acid on astrocyte differentiation of neural stem cells （NSCs） and the related mechanisms in vitro. DESIGN, TIME AND SETTING： A randomized, controlled, grouping experiment was performed in Tianjin Medical University between August 2007 and October 2008. MATERIALS： Folic acid and 5-bromo-2-deoxyuridine （BrdU） were obtained from Sigma, MO, USA. Primary antibodies [rabbit anti-rat nestin, β-tubulin-Ⅲ, glial fibrillary acidic protein, and neurogeninl （Ngnl）; mouse anti-rat BrdU and β-actin monoclonal antibodies] were purchased from Santa Cruz Biotechnology, USA. METHODS： At 6 days of NSC proliferation from 24-hour-old neonatal rats, BrdU incorporation assay was performed. Seven days after primary culture, NSCs were induced to differentiate with medium containing 5% fetal bovine serum. Cultured NSCs were assigned to three groups： control, low-dose （liquid media with 8 mg/L folic acid）, and high-dose folic acid （liquid media with 44 mg/L folic acid）. MAIN OUTCOME MEASURES： At day 7 after primary culture, the cells were identified as NSCs by immunocytochemical methods. Double-label immunofluorescence technique for glial fibrillary acidic protein/BrdU detected differentiated cells 7 days after induction. Western blot was used to analyze expression of Ngnl protein in NSCs. RESULTS： In serum-free suspension medium, neurospheres comprised a large number of Nestin-, glial fibrillary acidic protein-, β-tubulin-Ⅲ-, and BrdU-positive cells. Compared with the control group, high-dose folic acid supplementation led to an marked increase in the percentage of glial fibrillary acidic protein/BrdU-positive cells （P 〈 0.05）, and significantly decreased Ngnl protein expression （P 〈 0.05）. CONCLUSION： Folic acid promotes astrocytic differentiation of NSCs, which might be related to downregulation of Ngnl protein expression.展开更多
Capture and detection of metastatic cancer cells are crucial for diagnosis and treatment of malignant neoplasm. Here, we report the use of folic acid （FA） modified electrospun poly（vinyl alcohol） （PVA）/polyethyl...Capture and detection of metastatic cancer cells are crucial for diagnosis and treatment of malignant neoplasm. Here, we report the use of folic acid （FA） modified electrospun poly（vinyl alcohol） （PVA）/polyethyleneimine （PEI） nanofibers for cancer cell capture applications. Electrospun PVA/PEI nanofibers crosslinked by glutaraldehyde vapor were modified with FA via a poly（ethylene glycol） （PEG） spacer, followed by acetylation of the fiber surface PEI amines. The formed FA-modified nanofibers were well characterized. The morphology of the electrospun PVA/PEI nanofibers is smooth and uniform despite the surface modification. In addition, the FA-modified nanofibers display good hemocompatibility as confirmed by hemolysis assay. Importantly, the developed FA-modified nanofibers are able to specifically capture cancer cells overexpressing FA receptors, which were validated by quantitative cell counting assay and qualitative confocal microscopy analysis. The developed FA-modified PVA/PEI nanofibers may be used for capturing circulating tumor cells for cancer diagnosis applications.展开更多
Neural tube defects(NTDs) are a group of congenital malformations of the central nervous system that are caused by the closure failure of the embryonic neural tube by the 28 th day of conception. Anencephaly and spina...Neural tube defects(NTDs) are a group of congenital malformations of the central nervous system that are caused by the closure failure of the embryonic neural tube by the 28 th day of conception. Anencephaly and spina bifida are the two major subtypes. Fetuses with anencephaly are often stillborn or electively aborted due to prenatal diagnosis, or they die shortly after birth. Most infants with spina bifida are live-born and, with proper surgical treatment, can survive into adulthood. However, these children often have life-long physical disabilities. China has one of the highest prevalence of NTDs in the world. Inadequate dietary folate intake is believed to be the main cause of the cluster. Unlike many other countries that use staple fortification with folic acid as the public health strategy to prevent NTDs, the Chinese government provides all women who have a rural household registration and who plan to become pregnant with folic acid supplements, free of charge, through a nation-wide program started in 2009. Two to three years after the initiation of the program, the folic acid supplementation rate increased to 85% in the areas of the highest NTD prevalence. The mean plasma folate level of women during early and mid-pregnancy doubled the level before the program was introduced. However, most women began taking folic acid supplements when they knew that they were pregnant. This is too late for the protection of the embryonic neural tube. In a postprogram survey of the women who reported folic acid supplementation, less than a quarter of the women began taking supplements prior to pregnancy, indicating that the remaining three quarters of the fetuses remained unprotected during the time of neural tube formation. Therefore, staple food fortification with folic acid should be considered as a priority in the prevention of NTDs.展开更多
After peripheral nerve injury, intraperitoneal injection of folic acid improves axon quantity, increases axon density and improves electromyography results. However, the mechanisms for this remain unclear. This study ...After peripheral nerve injury, intraperitoneal injection of folic acid improves axon quantity, increases axon density and improves electromyography results. However, the mechanisms for this remain unclear. This study explored whether folic acid promotes peripheral nerve injury repair by affecting Schwann cell function. Primary Schwann cells were obtained from rats by in vitro separation and culture. Cell proliferation, assayed using the Cell Counting Kit-8 assay, was higher in cells cultured for 72 hours with 100 mg/L folic acid compared with the control group. Cell proliferation was also higher in the 50, 100, 150, and 200 mg/L folic acid groups compared with the control group after culture for 96 hours. Proliferation was markedly higher in the 100 mg/L folic acid group compared with the 50 mg/L folic acid group and the 40 ng/L nerve growth factor group. In Transwell assays, the number of migrated Schwann cells dramatically increased after culture with 100 and 150 mg/L folic acid compared with the control group. In nerve growth factor enzyme-linked immunosorbent assays, treatment of Schwa nn cell cultures with 50, 100, and 150 mg/L folic acid increased levels of nerve growth factor in the culture medium compared with the control group at 3 days. The nerve growth factor concentration of Schwann cell cultures treated with 100 mg/L folic acid group was remarkably higher than that in the 50 and 150 mg/L folic acid groups at 3 days. Nerve growth factor concentration in the 10, 50, and 100 mg/L folic acid groups was higher than that in the control group at 7 days. The nerve growth factor concentration in the 50 mg/L folic acid group was remarkably higher than that in the 10 and 100 mg/L folic acid groups at 7 days. In vivo, 80 μg/kg folic acid was intraperitoneally administrated for 7 consecutive days after sciatic nerve injury. Immunohistochemical staining showed that the number of Schwann cells in the folic acid group was greater than that in the control group. We suggest that folic acid may play a role in improving the repair of peripheral nerve injury by promoting the proliferation and migration of Schwann cells and the secretion of nerve growth factors.展开更多
In this study, a targeting micellar drug delivery system was developed for intravesical instilled chemotherapy of bladder cancer. The amphiphilic diblock copolymer poly（？-caprolactone）-block-poly（ethylene glycol）...In this study, a targeting micellar drug delivery system was developed for intravesical instilled chemotherapy of bladder cancer. The amphiphilic diblock copolymer poly（？-caprolactone）-block-poly（ethylene glycol）（PCL-b-PEO） with functional amino group（NH2） at the end of PEO block was synthesized. Then the copolymer was conjugated with folic acid（FA） and fluorescein isothiocyannate（FITC） via the PEO-NH2 terminus, and then assembled into micelles with the target moiety and fluorescence labeling. In addition, drug loaded micelles were also fabricated with anticancer drug doxorubicin（DOX） encapsulated in the hydrophobic core. The micelles were characterized in terms of size, drug loaded efficiency and critical micellization concentration（CMC） by means of DLS, UV and fluorescence spectra. In vitro cellular uptake and cytotoxicity studies showed that FA modified PCL-b-PEO-FA micelles have a greater targeting efficiency to human bladder cancer cell（T-24 cell） compared to PCL-b-PEO-NH2 micelles due to the conjugation of FA on the surface, while no targeting effect to normal tissue originated human embryonic kidney 293（HEK-293） cells was observed, enabling the micelles a promising drug carrier for intravesical instilled chemotherapy of bladder cancer.展开更多
BACKGROUND Folic acid has been shown to improve non-alcoholic steatohepatitis(NASH),but its roles in hepatic lipid metabolism,hepatic one-carbon metabolism,and gut microbiota are still unknown.AIM To demonstrate the r...BACKGROUND Folic acid has been shown to improve non-alcoholic steatohepatitis(NASH),but its roles in hepatic lipid metabolism,hepatic one-carbon metabolism,and gut microbiota are still unknown.AIM To demonstrate the role of folic acid in lipid metabolism and gut microbiota in NASH.METHODS Twenty-four Sprague-Dawley rats were assigned into three groups:Chow diet,high-fat diet(HFD),and HFD with folic acid administration.At the end of 16 wk,the liver histology,the expression of hepatic genes related to lipid metabolism,one-carbon metabolism,and gut microbiota structure analysis of fecal samples based on 16 S r RNA sequencing were measured to evaluate the effect of folic acid.Palmitic acid-exposed Huh7 cell line was used to evaluate the role of folic acid in hepatic lipid metabolism.RESULTS Folic acid treatment attenuated steatosis,lobular inflammation,and hepatocellular ballooning in rats with HFD-induced steatohepatitis.Genes related to lipid de novo lipogenesis,β-oxidation,and lipid uptake were improvedin HFD-fed folic acid-treated rats.Furthermore,peroxisome proliferator-activated receptor alpha(PPARα)and silence information regulation factor 1(SIRT1)were restored by folic acid in HFD-fed rats and palmitic acid-exposed Huh7 cell line.The restoration of PPARαby folic acid was blocked after transfection with SIRT1 si RNA in the Huh7 cell line.Additionally,folic acid administration ameliorated depleted hepatic one-carbon metabolism and restored the diversity of the gut microbiota in rats with HFD-induced steatohepatitis.CONCLUSION Folic acid improves hepatic lipid metabolism by upregulating PPARαlevels via a SIRT1-dependent mechanism and restores hepatic one-carbon metabolism and diversity of gut microbiota,thereby attenuating HFD-induced NASH in rats.展开更多
AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenom...AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps. METHODS: In the current double-blind, placebo-controlled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years. RESULTS: Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 (SD, 0.69) for folic acid treated patients compared to 0.82 (SD, 1.17) for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonicadenomas or advanced adenomas responded better to folic acid supplementation. CONCLUSION: High dose folic acid supplementation is associated with a signif icant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia.展开更多
This study evaluated the effects of palm fat powder(PFP) and coated folic acid(CFA) on growth performance, ruminal fermentation, nutrient digestibility, microbial enzyme activity, microflora, hepatic lipid content and...This study evaluated the effects of palm fat powder(PFP) and coated folic acid(CFA) on growth performance, ruminal fermentation, nutrient digestibility, microbial enzyme activity, microflora, hepatic lipid content and gene expression in dairy bulls. Forty-eight Chinese Holstein bulls((362±12.4) days of age and(483±27.1) kg of body weight(BW)) were assigned to four groups in a completely randomized design with a 2×2 factorial arrangements. Supplemental PFP(0 or 30 g PFP kg-1 dietary dry matter(DM)) and CFA(0 or 120 mg FA d-1 as CFA) were mixed into the top one-third of a total mixed ration. The study included a 20-day adaptation period and followed by a 90-day collection period. The lower(P<0.01) feed conversion ratio with PFP or CFA addition resulted from the constant DM intake and the higher(P<0.05) average daily gain. The higher(P<0.05) ruminal p H, ether extract digestibility, microbial α-amylase activity, Butyrivibrio fibrisolvens copy, and expression of peroxisome-proliferator-activated receptor α(PPARα) and carnitine palmitoyl transferase-1(CPT1), and lower ruminal total volatile fatty acids(VFA) concentration, acetate to propionate ratio, neutral detergent fibre(NDF) digestibility, copies of total protozoa and Ruminococcus flavefaciens, and expression of sterol regulatory element binding protein-1(SREBP1) and acetyl-coenzyme A carboxylase α(ACACA) were observed for PFP addition. Supplementation with CFA increased(P<0.05) ruminal total VFA concentration, acetate to propionate ratio, digestibility of DM, organic matter, crude protein and NDF, activity of cellobiase, pectinase and α-amylase, copies of selected microbial except for total protozoa, as well as expression of PPARα, but decreased(P<0.05) ruminal p H, and expression of SREBP1 and ACACA. The PFP×CFA interaction(P<0.05) was observed for ammonia N, hepatic TG content, and m RNA expression of CPT1 and FAS. There had no significant difference in hepatic TG content when CFA was supplemented in the diet without PFP addition, the lower(P=0.001) hepatic TG content was observed when CFA was supplemented in the diet with PFP addition. The higher(P<0.05) m RNA expression of CPT1, and the lower(P<0.05) m RNA expression of FAS and ammonia N concentration were observed when CFA was supplemented in diet either without or with PFP addition. The results indicated that supplementation of CFA in PFP diet was more effective on increasing hepatic CPT1 expression, and decreasing ammonia N, hepatic TG content and FAS expression than in diet without PFP. Supplementation with PFP or CFA improved growth performance of dairy bulls by promoting nutrient utilization, microbial enzyme activity, microflora, and hepatic gene expression.展开更多
We encapsulated vincristine into folic acid-conjugated PEGylated liposomes to improve the anti-tumor efficacy on multidrug resistant cancers.It was observed that the drug delivery system we constructed exhibited maxim...We encapsulated vincristine into folic acid-conjugated PEGylated liposomes to improve the anti-tumor efficacy on multidrug resistant cancers.It was observed that the drug delivery system we constructed exhibited maximum cytotoxicity on KBv200 cells(multidrug resistant variant)compared with any other formulations.The semi-quantitative analysis of region of interest revealed that there was a great increase in area under curve(AUC)of a near-infrared fluorescein in solid tumors due to folic acid-mediated accumulation.Folic acid-conjugated PEGylated liposomes showed a significant tumor growth inhibiting effect in vitro and in vivo.TUNEL assay revealed that folic acid-conjugated PEGylated liposomes could induce cell apoptosis much more greatly than others.This study demonstrated that it had potential application prospective for the treatment of multidrug resistant cancer.展开更多
Efficient and robust single-atom catalysts(SACs)based on cheap and earth-abundant elements are highly desirable for electrochemical reduction of nitrogen to ammonia(NRR)under ambient conditions.Herein,for the first ti...Efficient and robust single-atom catalysts(SACs)based on cheap and earth-abundant elements are highly desirable for electrochemical reduction of nitrogen to ammonia(NRR)under ambient conditions.Herein,for the first time,a Mn-N-C SAC consisting of isolated manganese atomic sites on ultrathin carbon nanosheets is developed via a template-free folic acid self-assembly strategy.The spontaneous molecular partial dissociation enables a facile fabrication process without being plagued by metal atom aggregation.Thanks to well-exposed atomic Mn active sites anchored on two-dimensional conductive carbon matrix,the catalyst exhibits excellent activity for NRR with high activity and selectivity,achieving a high Faradaic efficiency of 32.02%for ammonia synthesis at−0.45 V versus reversible hydrogen electrode.Density functional theory calculations unveil the crucial role of atomic Mn sites in promoting N_(2) adsorption,activation and selective reduction to NH_(3) by the distal mechanism.This work provides a simple synthesis process for Mn-N-C SAC and a good platform for understanding the structure-activity relationship of atomic Mn sites.展开更多
Folic acid conjugated chitosan was prepared by cross-linking reaction with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride(EDC), and then used as a template to prepare folic acid-chitosan(FA-CS) conjugate...Folic acid conjugated chitosan was prepared by cross-linking reaction with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride(EDC), and then used as a template to prepare folic acid-chitosan(FA-CS) conjugated nanoparticles and load mitoxantrone nanoparticles(FA-CSNP/MTX). Drug dissolution testing, CCK-8 method, and confocal microscopy were used to detect their controlled-release capability in different situations and the specific uptake by HONE1 cells. The experimental results show that the nanoparticles have uniform size distribution of 48-58 nm. The highest encapsulation rate of the particles on mitoxantrone hydrochloride(MTX) is(77.5±1.9)%, and the drug loading efficiency is(18.4±0.4)%. The sustained release effect, cell growth inhibition activity and targeting effect of the FA-CS/MTX nanoparticles are good in artificial gastric fluid and intestinal fluid. It is demonstrated that the FA-CSNP system is a potentially useful system for the targeted delivery of anticancer drug MTX.展开更多
文摘Herein,a one-pot chemical reduction method was reported to prepare folic acid(FA)-stabilized silver nanoclusters(FA@Ag NCs),in which FA,hydrazine hydrate,and silver nitrate were used as capping agent,reducing agent,and precursor,respectively.Several technologies were employed to investigate the structures and optical properties of FA@Ag NCs,including transmission electron microscopy(TEM),X-ray photoelectron spectrometer(XPS),Fourier transform infrared spectrometer(FTIR),X-ray diffractometer(XRD),fluorescence spectrometer,and ultraviolet visible absorption spectrometer.FA@Ag NCs were suggested to be highly dispersed and spherical with a size of around 2.8 nm.Moreover,the maximum excitation and emission wavelengths of FA@Ag NCs were 370 and 447 nm,respectively.Under the optimal detection conditions,FA@Ag NCs could be used to effectively detect malachite green with the linear detection range of 0.5-200μmol·L^(-1).The detection limit was 0.084μmol·L^(-1).The fluorescence-quenching mechanism was ascribed to the static quenching.The detection system based on FA@AgNCs was successfully used for the detection of malachite green in actual samples with good accuracy and reproducibility.
基金supported by the National Natural Science Foundation of China(Nos.82373817 and 82003659)Shanghai Natural Science Foundation(No.23ZR1477500)Pudong Health Bureau of Shanghai(No.YC-2023-0401)。
文摘As PEGylated liposomes have witnessed remarkable advancements in drug delivery,their immunogenicity has emerged as a notable challenge.In this study,we discovered that a simple pre-injection of folic acid(FA)effectively mitigated the immunogenicity of PEGylated liposomes and enhanced their in vivo performance by tolerating splenic marginal zone B cells.FA specifically inhibited the internalization of PEGylated liposomes by splenic marginal zone B cells,thereby reducing splenic lymphocyte proliferation and specific IgM secretion.This modulation alleviated Ig M-mediated accelerated blood clearance and adverse accumulation of the PEGylated liposomes in the skin.These findings provide new insights into the immunomodulatory effects of FA and promising avenues to enhance the efficacy and safety of PEGylated liposomal nanomedicines.
基金funded by the Natural Science Foundation of Hunan Province(grant number 2024JJ5283 to XH)。
文摘Preterm birth and suboptimal fetal growth remain significant perinatal challenges worldwide.Recent data indicate that China's perinatal profile has improved due to reductions in preterm birth rates.However,the country has a 6.5%prevalence of small-for-gestational-age(SGA),ranking fifth globally in total SGA birth numbers^([1,2]).
基金supported by the National Natural Science Foundation of China (Nos.32071301,31971234 and 42177411)the Natural Science Foundation of Fujian Province,China (No.2020J01027)。
文摘Tributyltin(TBT),a common organotin environmental pollutant,may pose a threat to human development during critical early-life periods.We aimed to assess the neurodevelopmental intergenerational toxicity of early-life exposure to TBT and the protective effect of DNA methyl donor folic acid(FA).Specifically,after early-life exposure(1–21 days postfertilization,dpf)to TBT(0,1,10 and 100 ng/L),zebrafish(Danio rerio)were cultured in clean medium until sexual maturity.The exposed females were mated with unexposed males to produce embryos(F1).The F1 generation were cultured(4–120 hours post-fertilization,hpf)with and without 1 mmol/L FA.The neurotoxic effects of early-life TBT exposure for zebrafish and their offspring(F1)were significantly enhanced anxiety and reduced aggression,decreased gene expression of DNA methyltransferase in the brain and increased serotonin levels in the body.Moreover,the intergenerational neurodevelopmental toxicity,as manifested in the F1 generation,was attenuated by FA supplementation.In summary,early-life TBT exposure led to intergenerational neurodevelopmental deficits in zebrafish,and DNA methyl donors had a protective effect on F1 neurodevelopment,which can inform the prevention and treatment of intergenerational neurotoxicity due to organotin pollutants.
基金supported by the National Natural Science Foundation of China(Nos.32222046 and 82172630)the Key R&D Projects of the Science and Technology Department of Sichuan Province(No.2021YFS0235)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(Nos.ZYJC21022 and 2019HXFH017)。
文摘Oral squamous cell carcinoma(OSCC)is known as one of the most malignant tumors with high recurrence and fatality rate.The poor tumor-targeting ability of traditional chemotherapeutic drugs has been a grand challenge for anti-OSCC therapy.Beyond that,a large quantity of tumor associated macrophages in OSCC tissues further diminish the anti-tumor effects of these drugs.Therefore,we produced a therapeutic nano drug delivery system(FA-PEG-PLA-JQ1)through encapsulating JQ1[a small-molecule inhibitor of bromodomain containing protein 4(BRD4)]into the folic acid(FA)-modified nanoparticle(PEG-PLA),which could prolong the half-life of JQ1 and target the tumor tissues.And then,JQ1 released from this nanoparticle could prevent OSCC growth inducing tumor cell apoptosis,inhibiting tumor angiogenesis and the polarization of M2 type macrophages.In conclusion,our date demonstrated the therapeutic benefits of FA-PEG-PLA-JQ1 against OSCC in vivo or in vitro,which could be a novel treatment strategy for OSCC in coming days.
基金funded by Ministry of Higher Education(MOHE),Malaysia-Prototype Development Research Grant Scheme,Grant Number PRGS/1/2020/STG05/UM/02/1.
文摘The study focuses on the development of biocompatible and stable FA-functionalized nanocrystalline cellulose(NCC)as a potential drug delivery system for targeting folate receptor-positive cancer cells.The FA-functionalized NCCs were synthesized through a series of chemical reactions,resulting in nanoparticles with favorable properties for biomedical applications.The microstructural analysis revealed that the functionalized NCCs maintained their rod-shaped morphology and displayed hydrodynamic diameters suitable for evading the mononuclear phagocytic system while being large enough to target tumor tissues.Importantly,these nanoparticles possessed a negative surface charge,enhancing their stability and repelling potential aggregation.The binding specificity of FA-functionalized NCCs to folate receptor-positive cancer cells was demonstrated through various assays.The free folic acid inhibition assay showed approximately 30%decrease in the binding of functionalized NCCs in the presence of just 5 mM free FA,confirming their selectivity for folate receptor-positive cells.Confocal microscopy further validated this specificity,as only cancer cells displayed significant binding of functionalized NCCs.Crucially,biocompatibility tests revealed that both NCCs and FA-functionalized NCCs had minimal effects on red blood cells,and they did not induce erythrocyte aggregation.Furthermore,cell viability assays demonstrated functionalized NCCs have selective cytotoxicity against colorectal cancer cells HT-29 and SW-620(68%–88%cell viability)while sparing noncancerous colon cells CCD-18Co(81%–97%cell viability).In summary,FA-functionalized NCCs exhibit promising characteristics for targeted drug delivery in cancer therapy.Their biocompatibility,stability,and selective cytotoxicity make them an attractive option for delivering therapeutic agents to folate receptor-positive cancer cells,potentially improving the effectiveness of cancer treatments while minimizing harm to healthy tissues.
基金The Medical Science and Technology Foundation of Chinese PLA during Twelfth "Five-year" Development Period(General Program),No. CWS11J003
文摘Folic acid participates in the metabolism of homocysteine and lowers plasma homocysteine levels directly or indirectly. To establish a hyperhomocysteinemic pregnant rat model, 2 mL of DL-homocysteine was administered daily by intraperitoneal injection at a dose of 200 mg/kg from day 10 to day 19 of gestation. Folic acid was administered by intragastric administration at a dose of 20 mg/kg during the period of preeclampsia induction. Results showed that systolic blood pressure, proteinuria/creatinine ratio, and plasma homocysteine levels in the hyperhomocysteinemic pregnant rats increased significantly, and that body weight and brain weight of rat pups significantly decreased. Folic acid supplementation markedly reversed the above-mentioned abnormal changes of hyperhomocysteinemic pregnant rats and rat pups. These findings suggest that folic acid can alleviate the symptoms of hyperhomocysteinemia- induced preeclampsia in pregnant rats without influencing brain development of rat pups.
基金Supported by the Science and Technology Foundation of the State Railway Ministry, No. J98Z034
文摘AIM: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions. METHODS: Thirty-eight patients, with premalignant gastric lesions including 18 colonic-type intestinal metaplasia (IM) and 20 mild or moderate dysplasia, were randomly divided into a treatment group (n = 19) receiving folic acid 10 mg thrice daily and a control group (n = 19) receiving sucralfate 1 000 mg thrice daily for 3 mo. All patients underwent endoscopies and four biopsies were taken prior to treatment and repeated after concluding therapy. Folate concentrations in gastric mucosa were measured with chemiluminescent enzyme immunoassay. Epithelial apoptosis and the expression of Bcl-2 and p53 protein in gastric mucosa were detected with flow cytometric assay. RESULTS: The mean of folate concentration in gastric mucosa was 9.03±3.37 μg/g wet wt in the folic acid treatment group, which was significantly higher than 6.83±3.02 μg/g wet wt in the control group. Both the epithelial apoptosis rate and the tumor suppressor p53 expression in gastric mucosa significantly increased after folic acid treatment. In contrast, the expression of Bcl-2 oncogene protein decreased after folic acid therapy. CONCLUSION: These data indicate that folic acid may play an important role in the chemoprevention of gastric carcinogenesis by enhancing gastric epithelial apoptosis in the patients with premalignant lesions.
基金the National Natural Science Foundation of China,No.30571563, 30771797the grant from Tianjin Education Commission,China,No. 20070208
文摘BACKGROUND： Folic acid is essential for normal functioning of the nervous system. Previous studies have focused on the effects of folic acid on astrocyte proliferation. OBJECTIVE： To explore the effects of folic acid on astrocyte differentiation of neural stem cells （NSCs） and the related mechanisms in vitro. DESIGN, TIME AND SETTING： A randomized, controlled, grouping experiment was performed in Tianjin Medical University between August 2007 and October 2008. MATERIALS： Folic acid and 5-bromo-2-deoxyuridine （BrdU） were obtained from Sigma, MO, USA. Primary antibodies [rabbit anti-rat nestin, β-tubulin-Ⅲ, glial fibrillary acidic protein, and neurogeninl （Ngnl）; mouse anti-rat BrdU and β-actin monoclonal antibodies] were purchased from Santa Cruz Biotechnology, USA. METHODS： At 6 days of NSC proliferation from 24-hour-old neonatal rats, BrdU incorporation assay was performed. Seven days after primary culture, NSCs were induced to differentiate with medium containing 5% fetal bovine serum. Cultured NSCs were assigned to three groups： control, low-dose （liquid media with 8 mg/L folic acid）, and high-dose folic acid （liquid media with 44 mg/L folic acid）. MAIN OUTCOME MEASURES： At day 7 after primary culture, the cells were identified as NSCs by immunocytochemical methods. Double-label immunofluorescence technique for glial fibrillary acidic protein/BrdU detected differentiated cells 7 days after induction. Western blot was used to analyze expression of Ngnl protein in NSCs. RESULTS： In serum-free suspension medium, neurospheres comprised a large number of Nestin-, glial fibrillary acidic protein-, β-tubulin-Ⅲ-, and BrdU-positive cells. Compared with the control group, high-dose folic acid supplementation led to an marked increase in the percentage of glial fibrillary acidic protein/BrdU-positive cells （P 〈 0.05）, and significantly decreased Ngnl protein expression （P 〈 0.05）. CONCLUSION： Folic acid promotes astrocytic differentiation of NSCs, which might be related to downregulation of Ngnl protein expression.
基金financially supported by the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learningthe Key Laboratory of Textile Science&Technology,Ministry of Education,“111 Project”(B07024)+4 种基金the Fundamental Research Funds for the Central Universitiesthe Chinese Universities Scientific Fund(No.101-06-0019014)the support from Shanghai Pujiang Program(No.14PJ1400400)the National Natural Science Foundation of China(No.21405012)the State Key Laboratory for Modification of Chemical Fibers and Polymer Materials,Donghua University(No.LK1429)
文摘Capture and detection of metastatic cancer cells are crucial for diagnosis and treatment of malignant neoplasm. Here, we report the use of folic acid （FA） modified electrospun poly（vinyl alcohol） （PVA）/polyethyleneimine （PEI） nanofibers for cancer cell capture applications. Electrospun PVA/PEI nanofibers crosslinked by glutaraldehyde vapor were modified with FA via a poly（ethylene glycol） （PEG） spacer, followed by acetylation of the fiber surface PEI amines. The formed FA-modified nanofibers were well characterized. The morphology of the electrospun PVA/PEI nanofibers is smooth and uniform despite the surface modification. In addition, the FA-modified nanofibers display good hemocompatibility as confirmed by hemolysis assay. Importantly, the developed FA-modified nanofibers are able to specifically capture cancer cells overexpressing FA receptors, which were validated by quantitative cell counting assay and qualitative confocal microscopy analysis. The developed FA-modified PVA/PEI nanofibers may be used for capturing circulating tumor cells for cancer diagnosis applications.
文摘Neural tube defects(NTDs) are a group of congenital malformations of the central nervous system that are caused by the closure failure of the embryonic neural tube by the 28 th day of conception. Anencephaly and spina bifida are the two major subtypes. Fetuses with anencephaly are often stillborn or electively aborted due to prenatal diagnosis, or they die shortly after birth. Most infants with spina bifida are live-born and, with proper surgical treatment, can survive into adulthood. However, these children often have life-long physical disabilities. China has one of the highest prevalence of NTDs in the world. Inadequate dietary folate intake is believed to be the main cause of the cluster. Unlike many other countries that use staple fortification with folic acid as the public health strategy to prevent NTDs, the Chinese government provides all women who have a rural household registration and who plan to become pregnant with folic acid supplements, free of charge, through a nation-wide program started in 2009. Two to three years after the initiation of the program, the folic acid supplementation rate increased to 85% in the areas of the highest NTD prevalence. The mean plasma folate level of women during early and mid-pregnancy doubled the level before the program was introduced. However, most women began taking folic acid supplements when they knew that they were pregnant. This is too late for the protection of the embryonic neural tube. In a postprogram survey of the women who reported folic acid supplementation, less than a quarter of the women began taking supplements prior to pregnancy, indicating that the remaining three quarters of the fetuses remained unprotected during the time of neural tube formation. Therefore, staple food fortification with folic acid should be considered as a priority in the prevention of NTDs.
基金supported by the High Levels of Health Technical Personnel in Beijing City Health System of China,No.2013-3-050(to JZY)
文摘After peripheral nerve injury, intraperitoneal injection of folic acid improves axon quantity, increases axon density and improves electromyography results. However, the mechanisms for this remain unclear. This study explored whether folic acid promotes peripheral nerve injury repair by affecting Schwann cell function. Primary Schwann cells were obtained from rats by in vitro separation and culture. Cell proliferation, assayed using the Cell Counting Kit-8 assay, was higher in cells cultured for 72 hours with 100 mg/L folic acid compared with the control group. Cell proliferation was also higher in the 50, 100, 150, and 200 mg/L folic acid groups compared with the control group after culture for 96 hours. Proliferation was markedly higher in the 100 mg/L folic acid group compared with the 50 mg/L folic acid group and the 40 ng/L nerve growth factor group. In Transwell assays, the number of migrated Schwann cells dramatically increased after culture with 100 and 150 mg/L folic acid compared with the control group. In nerve growth factor enzyme-linked immunosorbent assays, treatment of Schwa nn cell cultures with 50, 100, and 150 mg/L folic acid increased levels of nerve growth factor in the culture medium compared with the control group at 3 days. The nerve growth factor concentration of Schwann cell cultures treated with 100 mg/L folic acid group was remarkably higher than that in the 50 and 150 mg/L folic acid groups at 3 days. Nerve growth factor concentration in the 10, 50, and 100 mg/L folic acid groups was higher than that in the control group at 7 days. The nerve growth factor concentration in the 50 mg/L folic acid group was remarkably higher than that in the 10 and 100 mg/L folic acid groups at 7 days. In vivo, 80 μg/kg folic acid was intraperitoneally administrated for 7 consecutive days after sciatic nerve injury. Immunohistochemical staining showed that the number of Schwann cells in the folic acid group was greater than that in the control group. We suggest that folic acid may play a role in improving the repair of peripheral nerve injury by promoting the proliferation and migration of Schwann cells and the secretion of nerve growth factors.
基金financially supported by the National Natural Science Foundation of China(Nos.51503013,51390481,and 81472412)the Ministry of Finance and the Ministry of Education of PRC for BUCT
文摘In this study, a targeting micellar drug delivery system was developed for intravesical instilled chemotherapy of bladder cancer. The amphiphilic diblock copolymer poly（？-caprolactone）-block-poly（ethylene glycol）（PCL-b-PEO） with functional amino group（NH2） at the end of PEO block was synthesized. Then the copolymer was conjugated with folic acid（FA） and fluorescein isothiocyannate（FITC） via the PEO-NH2 terminus, and then assembled into micelles with the target moiety and fluorescence labeling. In addition, drug loaded micelles were also fabricated with anticancer drug doxorubicin（DOX） encapsulated in the hydrophobic core. The micelles were characterized in terms of size, drug loaded efficiency and critical micellization concentration（CMC） by means of DLS, UV and fluorescence spectra. In vitro cellular uptake and cytotoxicity studies showed that FA modified PCL-b-PEO-FA micelles have a greater targeting efficiency to human bladder cancer cell（T-24 cell） compared to PCL-b-PEO-NH2 micelles due to the conjugation of FA on the surface, while no targeting effect to normal tissue originated human embryonic kidney 293（HEK-293） cells was observed, enabling the micelles a promising drug carrier for intravesical instilled chemotherapy of bladder cancer.
基金Supported by National Key R&D Program of China,No.2017YFC0908903National Natural Science Foundation of China,No.81873565,No.81470840,and No.81700503.
文摘BACKGROUND Folic acid has been shown to improve non-alcoholic steatohepatitis(NASH),but its roles in hepatic lipid metabolism,hepatic one-carbon metabolism,and gut microbiota are still unknown.AIM To demonstrate the role of folic acid in lipid metabolism and gut microbiota in NASH.METHODS Twenty-four Sprague-Dawley rats were assigned into three groups:Chow diet,high-fat diet(HFD),and HFD with folic acid administration.At the end of 16 wk,the liver histology,the expression of hepatic genes related to lipid metabolism,one-carbon metabolism,and gut microbiota structure analysis of fecal samples based on 16 S r RNA sequencing were measured to evaluate the effect of folic acid.Palmitic acid-exposed Huh7 cell line was used to evaluate the role of folic acid in hepatic lipid metabolism.RESULTS Folic acid treatment attenuated steatosis,lobular inflammation,and hepatocellular ballooning in rats with HFD-induced steatohepatitis.Genes related to lipid de novo lipogenesis,β-oxidation,and lipid uptake were improvedin HFD-fed folic acid-treated rats.Furthermore,peroxisome proliferator-activated receptor alpha(PPARα)and silence information regulation factor 1(SIRT1)were restored by folic acid in HFD-fed rats and palmitic acid-exposed Huh7 cell line.The restoration of PPARαby folic acid was blocked after transfection with SIRT1 si RNA in the Huh7 cell line.Additionally,folic acid administration ameliorated depleted hepatic one-carbon metabolism and restored the diversity of the gut microbiota in rats with HFD-induced steatohepatitis.CONCLUSION Folic acid improves hepatic lipid metabolism by upregulating PPARαlevels via a SIRT1-dependent mechanism and restores hepatic one-carbon metabolism and diversity of gut microbiota,thereby attenuating HFD-induced NASH in rats.
文摘AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps. METHODS: In the current double-blind, placebo-controlled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years. RESULTS: Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 (SD, 0.69) for folic acid treated patients compared to 0.82 (SD, 1.17) for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonicadenomas or advanced adenomas responded better to folic acid supplementation. CONCLUSION: High dose folic acid supplementation is associated with a signif icant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia.
基金supported by a grant from the Natural Science Funding Projects of Shanxi Province,China(201801D121241)the Animal Husbandry Dominant Key Discipline Construction Project in“1331 Project”of Shanxi Province,China。
文摘This study evaluated the effects of palm fat powder(PFP) and coated folic acid(CFA) on growth performance, ruminal fermentation, nutrient digestibility, microbial enzyme activity, microflora, hepatic lipid content and gene expression in dairy bulls. Forty-eight Chinese Holstein bulls((362±12.4) days of age and(483±27.1) kg of body weight(BW)) were assigned to four groups in a completely randomized design with a 2×2 factorial arrangements. Supplemental PFP(0 or 30 g PFP kg-1 dietary dry matter(DM)) and CFA(0 or 120 mg FA d-1 as CFA) were mixed into the top one-third of a total mixed ration. The study included a 20-day adaptation period and followed by a 90-day collection period. The lower(P<0.01) feed conversion ratio with PFP or CFA addition resulted from the constant DM intake and the higher(P<0.05) average daily gain. The higher(P<0.05) ruminal p H, ether extract digestibility, microbial α-amylase activity, Butyrivibrio fibrisolvens copy, and expression of peroxisome-proliferator-activated receptor α(PPARα) and carnitine palmitoyl transferase-1(CPT1), and lower ruminal total volatile fatty acids(VFA) concentration, acetate to propionate ratio, neutral detergent fibre(NDF) digestibility, copies of total protozoa and Ruminococcus flavefaciens, and expression of sterol regulatory element binding protein-1(SREBP1) and acetyl-coenzyme A carboxylase α(ACACA) were observed for PFP addition. Supplementation with CFA increased(P<0.05) ruminal total VFA concentration, acetate to propionate ratio, digestibility of DM, organic matter, crude protein and NDF, activity of cellobiase, pectinase and α-amylase, copies of selected microbial except for total protozoa, as well as expression of PPARα, but decreased(P<0.05) ruminal p H, and expression of SREBP1 and ACACA. The PFP×CFA interaction(P<0.05) was observed for ammonia N, hepatic TG content, and m RNA expression of CPT1 and FAS. There had no significant difference in hepatic TG content when CFA was supplemented in the diet without PFP addition, the lower(P=0.001) hepatic TG content was observed when CFA was supplemented in the diet with PFP addition. The higher(P<0.05) m RNA expression of CPT1, and the lower(P<0.05) m RNA expression of FAS and ammonia N concentration were observed when CFA was supplemented in diet either without or with PFP addition. The results indicated that supplementation of CFA in PFP diet was more effective on increasing hepatic CPT1 expression, and decreasing ammonia N, hepatic TG content and FAS expression than in diet without PFP. Supplementation with PFP or CFA improved growth performance of dairy bulls by promoting nutrient utilization, microbial enzyme activity, microflora, and hepatic gene expression.
基金This work was supported by National Science and Technology Major Project(2012ZX09304004)National Basic Research Program of China(973 Program,2010CB934000)+1 种基金National Natural Science Foundation of China(81072593,81102402)Specialized Research Fund for the Doctoral Program of Higher Education(20110071130011).
文摘We encapsulated vincristine into folic acid-conjugated PEGylated liposomes to improve the anti-tumor efficacy on multidrug resistant cancers.It was observed that the drug delivery system we constructed exhibited maximum cytotoxicity on KBv200 cells(multidrug resistant variant)compared with any other formulations.The semi-quantitative analysis of region of interest revealed that there was a great increase in area under curve(AUC)of a near-infrared fluorescein in solid tumors due to folic acid-mediated accumulation.Folic acid-conjugated PEGylated liposomes showed a significant tumor growth inhibiting effect in vitro and in vivo.TUNEL assay revealed that folic acid-conjugated PEGylated liposomes could induce cell apoptosis much more greatly than others.This study demonstrated that it had potential application prospective for the treatment of multidrug resistant cancer.
基金The authors thank the financial support from the National Natural Science Foundation of China(No.51902204,52001214,21975163)Bureau of Industry and Information Technology of Shenzhen(No.201901171518)Shenzhen Science and Technology Program(KQTD20190929173914967).
文摘Efficient and robust single-atom catalysts(SACs)based on cheap and earth-abundant elements are highly desirable for electrochemical reduction of nitrogen to ammonia(NRR)under ambient conditions.Herein,for the first time,a Mn-N-C SAC consisting of isolated manganese atomic sites on ultrathin carbon nanosheets is developed via a template-free folic acid self-assembly strategy.The spontaneous molecular partial dissociation enables a facile fabrication process without being plagued by metal atom aggregation.Thanks to well-exposed atomic Mn active sites anchored on two-dimensional conductive carbon matrix,the catalyst exhibits excellent activity for NRR with high activity and selectivity,achieving a high Faradaic efficiency of 32.02%for ammonia synthesis at−0.45 V versus reversible hydrogen electrode.Density functional theory calculations unveil the crucial role of atomic Mn sites in promoting N_(2) adsorption,activation and selective reduction to NH_(3) by the distal mechanism.This work provides a simple synthesis process for Mn-N-C SAC and a good platform for understanding the structure-activity relationship of atomic Mn sites.
基金Projects(31201074,81371013) supported by the National Natural Science Foundation of ChinaProject(2011105102016) supported by the Key Program of Medical Health of Dongguan City,Guangdong Province,ChinaProject(2011108102026) supported by Dongguan Universities Program,China
文摘Folic acid conjugated chitosan was prepared by cross-linking reaction with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride(EDC), and then used as a template to prepare folic acid-chitosan(FA-CS) conjugated nanoparticles and load mitoxantrone nanoparticles(FA-CSNP/MTX). Drug dissolution testing, CCK-8 method, and confocal microscopy were used to detect their controlled-release capability in different situations and the specific uptake by HONE1 cells. The experimental results show that the nanoparticles have uniform size distribution of 48-58 nm. The highest encapsulation rate of the particles on mitoxantrone hydrochloride(MTX) is(77.5±1.9)%, and the drug loading efficiency is(18.4±0.4)%. The sustained release effect, cell growth inhibition activity and targeting effect of the FA-CS/MTX nanoparticles are good in artificial gastric fluid and intestinal fluid. It is demonstrated that the FA-CSNP system is a potentially useful system for the targeted delivery of anticancer drug MTX.
