Mitigating the toxicity of reactive oxygen species induced by cadmium via restoring citrate valve and improving the stability of enzyme structure in rice.

The mechanism of reactive oxygen species (ROS) burst in rice cells induced by cadmium (Cd) stress remains poorly understood. The present study shows that the burst of superoxide anions (O2·-) and hydrogen peroxide (H2O2) in roots and shoots led by Cd stress was attributed to the disturbance of citrate (CA) valve and the damage of antioxidant enzyme structure in the rice seedlings. Cd accumulation in cells altered the molecular structure of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) through attacking glutamate (Glu) and other residues, leading to the significant reduction of their activities in clearing O2·- and decomposing H2O2. Citrate supplementation obviously increased the activity of antioxidant enzymes and decreased ∼20-30% of O2·- and H2O2 contents in roots and shoots. Meanwhile, the synthesis of metabolites/ligands such as CA, α-ketoglutarate (α-KG) and Glu as well as the activities of related enzymes in CA valve were remarkably improved. The activities of antioxidant enzymes were protected by CA through forming stable hydrogen-bonds between CA and antioxidant enzymes, and forming the stable chelates between ligands and Cd. These findings indicate that exogenous CA mitigated the toxicity of ROS under Cd stress by the ways of restoring CA valve function to reduce the production of ROS, and improving the stability of enzyme structure to enhance antioxidant enzymes activity.

Update on citric acid use in endodontic treatment: a systematic review.

This systematic review aims to analyse the available evidence concerning the use of citric acid (CA) in endodontics treatment and to assess its results in terms of different considerations: effect on smear layer removal, influence on sealer bond strength, activation effect by means of sonic or ultrasonic devices, effects on dentine surface, antibacterial activity, and effectiveness boost for regenerative procedures, releasing growth factors from dentin. To evaluate the results of CA as a final irrigant and compare them to other chelating agents. This review followed the PRISMA checklist. An electronic search was conducted in MEDLINE (OVID), Scopus (Elsevier) and the Web of Science (Thomson Reuters) databases. Risk of bias of included studies was evaluated using the modified CONSORT checklist and the PRIRATE checklist 2020 guidelines. 39 studies fulfilled the eligibility criteria to be included in this review: 27 in vitro studies using extracted human teeth, 10 in vitro studies using human dentin disks, and 2 RCT. Citric acid has proven to be effective in smear layer removal, showing better results in coronal and middle root thirds, improving its effect when combined with manual dynamic activation. There is no agreement regarding citric acid effect on sealer adhesion and adaptation to root canal walls due to heterogeneity within studies. Citric acid irrigation can decrease dentine microhardness and cause decalcification and erosion, especially when used before NaOCl. Citric acid has proven to be beneficial in regenerative endodontic procedures due to higher TGF-ß1 release.Trial registration: Prospero database CRD42021267055.

A mixture of organic acids and thymol protects primary chicken intestinal epithelial cells from Clostridium perfringens infection in vitro.

Necrotic enteritis causes economic losses estimated to be up to 6 billion US dollars per year. Clinical and subclinical infections in poultry are also both correlated with decreased growth and feed efficiency. Moreover, in a context of increased antibiotic resistance, feed additives with enhanced antimicrobial properties are a useful and increasingly needed strategy. In this study, the protective effects of a blend of thymol and organic acids against the effects of Clostridium perfringens type A (CP) on chicken intestinal epithelial cells were investigated and compared to bacitracin, a widely used antibiotic in poultry production. Primary chicken intestinal epithelial cells were challenged with CP for a total time of 3 h to assess the beneficial effect of 2 doses of citric acid, dodecanoic acid, and thymol-containing blend, and compare them with bacitracin. During the challenge, different parameters were recorded, such as transepithelial electrical resistance, cell viability, mRNA expression, and reactive oxygen species production. CP induced inflammation with cytokine production and loss of epithelial barrier integrity. It was also able to induce reactive oxygen species production and increase the caspase expression leading to cellular death. The high dose of the blend acted similarly to bacitracin, preventing the disruptive effects of CP and inducing also an increase in zonula occludens-1 mRNA expression. The low dose only partially prevented the disruptive effects of CP but successfully reduced the associated inflammation. This study shows that the usage of thymol combined with 2 organic acids can protect primary chicken intestinal epithelial cells from CP-induced damages creating a valid candidate to substitute or adjuvate the antibiotic treatment against necrotic enteritis.

Effect of Citric Acid Versus EDTA on Radiographic Root Development in Regenerative Endodontic Treatment: An Animal Study.

INTRODUCTION: Regenerative endodontic treatment was introduced with the aim of reinforcing the root and enabling further root development. In the process of dentin mineralization, bioactive molecules are entrapped in the dentin matrix, which can be released later by rinsing the dentin with chelating agents. This study aimed to compare the effects of citric acid and EDTA on radiographic root development in regenerative endodontic treatment in an animal model. METHODS: Premolars of 3 beagle dogs were used in this study. The teeth at 1 side of the jaw were irrigated with EDTA according to the regeneration protocol of the American Association of Endodontists. The teeth in the other quadrant were irrigated with citric acid in the second treatment session. Follow-up radiographs were obtained at 6 months, and the primary and final data were analyzed in SPSS Version 23 (IBM Corp, Armonk, NY) using the analysis of covariance. RESULTS: There was no significant difference between the 2 irrigating solutions regarding the increase in root length (P = .668); however, EDTA showed significantly superior efficacy in increasing the root dentin thickness compared with citric acid (P = .022). CONCLUSIONS: Within the limitations of this study, the use of citric acid versus EDTA was not superior on radiographic root development in regenerative endodontic treatment.

Effect of citric acid and heat treatment on the content of less-polar ginsenosides in flower buds of Panax ginseng.

Ginseng flower bud (GFB), as an inexpensive part of Panax ginseng, attracted significant attention as a beneficial functional food with medicinal potentials due to its high content of ginsenosides. A few studies focused on the utilization of heat treatment and citric acid treatment to process ginseng flowers, converting its polar ginsenosides into rare ginsenosides to improve its biological activities. Thus, in this study, we compared the changes of ginsenosides in GFB after citric acid and heat treatment by HPLC method. The results revealed that less-polar ginsenoside, Rg6 and F4, increased to 1.01 and 0.27% by heat treatment, respectively. Further, ginsenoside F2 increased to 1.13% with 1 M citric acid treatment. Furthermore, based on the combination of these two processing methods for the first time, the conversion rate of less-polar ginsenosides surged to 80%. The content of ginsenoside Rg3(s) and Rg5 increased to 1.509 and 1.871%, respectively, by simultaneous heat and citric acid treatment. Therefore, a processing approach that simultaneously performs heat and citric acid treatments has been proposed, and this considerably inexpensive and convenient processing method could be applied to the processing of GFBs and produce less-polar ginsenosides.

The effects of two different antioxidant combinations on sperm parameters.

BACKGROUND: Studies demonstrate that getting antioxidants in the course of treatment has a positive impact beneficial effect on fertility, especially on the quality of sperm. Because of that reason antioxidants are recommended as a potentially influential treatment for infertility in men. However, it is argued that this treatment is not based on sufficient evidence and has no effect on the rate of healthy pregnancy. OBJECTIVE: In this study, two different antioxidant combinations with different doses and contents were evaluated in terms of their effect on sperm parameters. MATERIALS/METHODS: A total of 122 patients diagnosed with idiopathic infertility were enrolled in our multicenter study. The patients were divided into two different groups: The first group used a combination 2 × 1 sachet form (l-carnitine 1 g, acetyl-l-carnitine 0.5 g, fructose 1 g, citric acid 0.50 mg, selenium 50 µg, coenzyme Q10 20 mg, vitamin C 90 mg, zinc 10 mg, folic acid 200 µg, and vitamin B12 1.5 µg) and the second group used a combination tablets form 2 × 1 (l-carnitine 500 mg, selenium 50 µg, coenzyme Q10 20 mg, vitamin C 60 mg, zinc 15 mg, folic acid 400 µg, vitamin E, and ginseng 15 µg) for 6 months. The total semen volume, the total sperm number, sperm concentration, sperm motility, and lastly morphological findings of the patients were compared at the end of 6 months. RESULTS: The mean age of the patients participating in the study was 30.8 ± 6.05 years. No significant difference was found between the two groups in terms of baseline sperm count. There was a significant difference between the baseline and sixth-month values of the patients using both combinations. However, no significant statistical difference was found between the groups according to the sixth-month data. The combinations of both antioxidants had a positive effect on sperm parameters, and the use of different doses and contents had a similar effect. CONCLUSION: Both antioxidants respectively had a positive effect on sperm parameters and also the use of different doses and contents had a similar effect.

Use of citric acid and garlic extract to inhibit Salmonella enterica and Listeria monocytogenes in hummus.

Recently, the consumption of hummus has become popular in the United States, European countries, and Canada, and unfortunately, several foodborne outbreaks and recalls have been reported due to its contamination with Listeria monocytogenes and Salmonella enterica. The current study aimed to investigate the inhibitory activity of 0.5, 1.0, and 1.5% citric acid (CA) and 1.0, 2.0 and 3.0% garlic extract (GE) toward S. enterica and L. monocytogenes in hummus stored at 4, 10 and 24 °C. L. monocytogenes grew well in untreated (control) hummus samples at all tested temperatures, whereas S. enterica grew only at 10 and 24 °C. CA at 0.5 to 1.5% reduced L. monocytogenes numbers by 3.0-3.3 log CFU/g at 4 °C, 1.7-3.9 log CFU/g at 10 °C, and 0.9-1.4 log CFU/g at 24 °C. Numbers of S. enterica were reduced by 0.6-1.7, 4.1-4.9 and <1.5 log CFU/g, at 4, 10 and 24 °C, respectively, compared to the control during 10 d storage. GE at 1.0-3.0% also reduced numbers of L. monocytogenes at 10 d by 0.7-3.0, and 1.3-3.6 log CFU/g at 4 and 10 °C, respectively, and numbers of S. enterica by 0.7-1.2, 1.8-2.6 and 0.5-1.6 log CFU/g, at 4, 10 and 24 °C, respectively, compared to the control. Chromatographic analysis of GE revealed the presence of four organosulfur compounds including diallyl disulfide, diallyl trisulfide, 2-vinyl-(4H)-1,3-dithiin and 3-vinyl-(4H)-1,2-dithiin where the latter was the predominant compound with a level of 22.9 mg/g which significantly contributed to the inhibitory effect of GE. CA and GE are adequate natural antimicrobials in hummus to reduce L. monocytogenes and S. enterica numbers and enhance product safety.

Dietary citrate supplementation enhances longevity, metabolic health, and memory performance through promoting ketogenesis.

Citrate is an essential substrate for energy metabolism that plays critical roles in regulating cell growth and survival. However, the action of citrate in regulating metabolism, cognition, and aging at the organismal level remains poorly understood. Here, we report that dietary supplementation with citrate significantly reduces energy status and extends lifespan in Drosophila melanogaster. Our genetic studies in fruit flies implicate a molecular mechanism associated with AMP-activated protein kinase (AMPK), target of rapamycin (TOR), and ketogenesis. Mice fed a high-fat diet that supplemented with citrate or the ketone body ß-hydroxybutyrate (ßOHB) also display improved metabolic health and memory. These results suggest that dietary citrate supplementation may prove to be a useful intervention in the future treatment of age-related dysfunction.

Role of Citrus Fruit Juices in Prevention of Kidney Stone Disease (KSD): A Narrative Review.

To explore the relationship between citrus fruit juices (oranges, grapefruits, and lemonades) and kidney stone disease (KSD). METHODS: A systematic review was performed using the Medline, EMBASE, and Scopus databases, in concordance with the PRISMA checklist for all English, French, and Spanish language studies regarding the consumption of citrus fruit juices and the relationship to urinary stone disease. The main outcome of interest was the association of citrus fruit juices with KSD. RESULTS: Thirteen articles met the criteria for inclusion in the final review. Three large epidemiological studies found that grapefruit juice was a risk factor for stone formation, while orange juice did not increase the risk for KSD. Ten small prospective clinical studies found that orange, grapefruit, and lemon juices all increased urinary citrate levels. Only orange and grapefruit juices had an alkalinizing effect and while lemon juice has a protective effect by raising urinary citrate levels, it lacked a significant alkalinizing effect on urine pH. Orange juice and grapefruit juices significantly increased urinary oxalate levels, while orange juice also had a high carbohydrate content. CONCLUSION: While orange juice seems to play a protective role against stone formation, grapefruit was found to raise the risk of KSD in epidemiological studies but had a protective role in smaller clinical studies. Lemon juice had a smaller protective role than orange juice. Larger amounts of, as well as more accurate, data is needed before recommendations can be made and a high carbohydrate content in these juices needs to be taken into consideration.

Bioremediation of hemotoxic and oxidative stress induced by polyethylene microplastic in Clarias gariepinus using lycopene, citric acid, and chlorella.

Despite extensive research on the toxic effects of microplastics (MPs), there is no obtainable data on the use of phytobioremediation against MPs toxicity in fish. This study aimed to investigate the protective role of lycopene, citric acid, and chlorella against the toxic effects of MPs in African catfish (Clarias gariepinus) using hematology, biochemical, antioxidants, erythron profiles (poikilocytosis and nuclear abnormalities) and the accumulation of MPs in tissues as biomarkers. Five groups of fish received: normal diet (control); MPs (500 mg/kg diet) (Group 2); MPs (500 mg/kg diet) + lycopene (500 mg/kg diet) (Group 3); MPs (500 mg/kg diet) + citric acid (30 g/kg diet) (Group 4); and MPs (500 mg/kg diet) + chlorella (50 g/kg diet) (Group 5) for 15 days. Group 2 had significantly higher amounts of MPs in the stomach, gills, and feces, electrolyte imbalances (HCO3, Fe, Na+, K+, Ca+2, Cl-, and anion gap, hematobiochemical alterations, and decreases in the activities of superoxide dismutase, catalase, total antioxidant capacity, and glutathione S-transferases compared to the control group. Additionally, Group 2 had significant increase in the percentage of poikilocytosis, and nuclear abnormalities in RBC's compared to the control group. The co-treatment of MPs-exposed fish with lycopene, citric acid, and chlorella-supplemented diets ameliorated the hematological, biochemical, and erythron profile alterations, but only slightly enhanced the antioxidant activity. Overall, lycopene, citric acid, and chlorella can be recommended as a feed supplement to improve hematobiochemical alterations and oxidative damage induced by MPs toxicity in the African catfish (C. gariepinus).

Effectiveness of supplemental oral calcium drink in preventing citrate-related adverse effects in peripheral blood progenitor cell collection.

Peripheral blood progenitor cells (PBPCs) are a predominant graft source in allogeneic hematopoietic cell transplantation. Citrate-induced hypocalcemia remains the most frequent side effect of PBPC apheresis. Although the method for preventing severe adverse events is established, more efficient prophylaxis is required so that volunteer donors can donate PBPCs without pain and anxiety. We studied 80 healthy donors who underwent PBPC harvest between February 2014 and June 2020. Of these, 23 donors who underwent apheresis between February 2014 and December 2015 received only the standard prophylaxis of intravenous calcium gluconate. Oral calcium drinks were provided to 57 donors who underwent apheresis from January 2016 to June 2020 to supplement intravenous calcium gluconate prophylaxis. The ionized calcium (ICa) levels at multiple time intervals and the hypocalcemic symptoms were evaluated. Oral supplementation with a calcium drink maintained significantly higher ICa levels. Analysis using the inverse probability weighted regression adjustment method suggested that calcium drinks reduced the frequency of citrate-related reactions by 39.2 %. Administering a prophylactic oral calcium drink before apheresis with intravenous administration of calcium gluconate is promising to further reduce citrate-induced hypocalcemia in volunteer donors.

Effect of plant extracts and citric acid on phytoremediation of metal-contaminated soil.

Application of activating agents can significantly improve efficiency of plants for remediation of soils contaminated by heavy metals, however, damage to soil and plants limits application of traditional activating agents. The aim of our experiments is to select an efficient,green and low-cost activating agent to improve efficiency of plant extraction technology. In this study, contaminated soil was remediated by Sedum alfredii. The effects of two plant extracts (i.e., Oxalis corniculata,OX and Medicago sativaextract, ME) in addition to citric acid (CA) were studied in oscillatory activation experiment and pot experiment. The oscillation activation experiment revealed that extraction quantity of heavy metals in the soil was enhanced significantly with concentration of plant extract. The extraction quantity of Zn from 100% OX extract and ME extract were significantly higher than 10 mmol/L CA (54.04% and 33.09%, respectively). The 10 mmol/L CA has best extraction efficiency for Cd, up to 41.36 µg/kg, which is significantly higher than CK (control) (p < 0.05). The pot experiment exhibited that application of CA has significantly reduced soil pH and organic matter content by 8.63% and 28.21%, respectively, however the two extracts have no significant effect on soil properties. The study indicated that application of CA has negative effects on root morphological parameters and chlorophyll fluorescence parameters of Sedum alfredii.The addition of extracts of two plants have not caused any harm to Sedum alfredii. The application of three activating agents was beneficial for purification of Cd and Zn in soils, and its repairing efficiency was improved by 3.92, 3.37, 3.33 times and 0.44, 0.20, 0.86 times, respectively. The combination of plant extracts and hyperaccumulators can effectively remove heavy metals from contaminated soils, which provided a theoretical basis for mitigation of pollution in soils.

In vitro evaluation of Labrador dog spermatozoa cryopreserved in Tris-citric acid-fructose buffer supplemented with different combinations of extracellular and intracellular cryoprotectants.

Aim of this study was to compare different combinations of penetrating intracellular CPAs, i.e., glycerol (G), ethylene glycol (EG), propylene glycol (PG), dimethyl formamide (DM), and methyl acetamide (MA) and extracellular [egg yolk (EY), egg yolk plasma (EYP), low-density lipoproteins (LDL), and coconut water (CW)] in Tris-citric acid-fructose buffer (T) for Labrador dog semen cryopreservation. The study was conducted in two parts, first trial was conducted to assess optimum glycerol concentration (5-7%) in TEY and equilibration time (ET, 2-4 hrs) for Labrador dog semen cryopreservation. Secondly, compatibility of 15% TEY, 15% TEYP, 13% TLDL, and 25% TCW with G, DMF, MA, D + M, EG, and PG was evaluated for in vitro sperm function tests. Decline in sperm attributes, i.e., motility, viability, plasma membrane integrity (PMI), and acrosome integrity (AI)) was significantly (p < 0.05) less in 7% TEY-G and 4 h compared to other concentrations and ET at post-thaw. There was significantly (p < 0.05) less decline in sperm attributes in TEY-G, TEYP-G, TLDL-G, TLDL-D, TLDL-EG, and TCW-D extenders compared to other combinations at post-thaw. However, these parameters were significantly (p < 0.05) high in TEY-G and TEYP-G compared to TEYP-D, TLDL-G, TLDL-D, TLDL-EG, and TCW-D extenders at post-thaw. However, decline in motility, viability, PMI, and AI was identical in these seven extenders. This study concluded that glycerol at a concentration of 7% in TEY and 4 h ET were optimum for successful cryopreservation and besides TEY-G, other combinations of protectants may be an alternative for canine semen cryopreservation.

Preparation of Sterile Raw Material - Chicken Eggshells in the Process of their Transformation into Selected Calcium Salts.

BACKGROUND: The chicken eggshells and their subcrustal membranes are a valuable source of calcium, but they are not further processed but disposed of as waste from the food industry. Chicken eggshells have high content (>95%) of calcium carbonate. Some properties suggest that eggshells may be a promising alternative to the present calcium sources used in the pharmaceutical industry. METHODS: The effect of roasting chicken eggshells with a selected organic acid (citric or fumaric or lactic acid) on microbiological purity, including the presence of fungi and bacteria Salmonella spp., Staphylococcus aureus, Escherichia coli of obtained calcium salts, was investigated. In this study, chicken eggshells were subjected to chemical reactions with organic acids (citric, fumaric or lactic acid) at two different calcium-acid molar ratios (1:1 or 1:3) and the mixture was heat-treated for 1 or 3 hours at a temperature of 100°C or 120°C. RESULTS AND DISCUSSION: It was found that lactic acid was 100% effective against fungi, and the remaining citric and fumaric acids were -50% (regardless of the other examined conditions). The type of acid used has a significant effect on fungal growth inhibition (p<0.05). Fumaric acid and lactic acid will be nearly 100% effective against bacteria (100% fumaric acid and 97% lactic acid effectiveness), regardless of other factors. CONCLUSION: Lactic acid is the most effective against pathogenic flora - fungi and bacteria. The transformation of chicken eggshells into calcium lactate can provide us with sterile calcium salt, free of 100% fungi and 97% of all bacteria.

Optimized calcium supplementation approach in post-dilution CVVHDF using regional citrate anticoagulation.

BACKGROUND: Regional citrate anticoagulation has been recommended as first choice for anticoagulation of continuous renal replacement therapy. Precise calcium supplementation is important for the safety of regional citrate anticoagulation. In this study we aimed to provide an optimized calcium supplementation approach for regional citrate anticoagulation in post-dilution continuous venous-venous hemodiafiltration. METHODS: Twenty-seven patients receiving post-dilution continuous venous-venous hemodiafiltration anticoagulated by citrate were included in this study. The ionized calcium levels were monitored and maintained in the targeted range. After linear regression analysis of the clearance of non-protein bound calcium and calculating the ratio of the non-protein bound calcium concentration to total calcium concentration, we concluded the mathematical model for calcium supplementation. RESULTS: Positive correlations were found between the clearance of non-protein bound calcium and both dialysate flow rates (r = 0.647, p < 0.001) and ultrafiltration plus substitution fluid flow rates (r = 0.525, p = 0.005). The ratio of the non-protein bound calcium concentration to total calcium concentration values at the pre-filter point after infusion of citrate were constant about 0.83. Based on the clearance and the calcium ratio, the amount of extracorporeal calcium removal can be estimated with a simplified equation. CONCLUSIONS: We provided an optimized calcium supplementation approach for post-dilution continuous venous-venous hemodiafiltration anticoagulated by citrate which may help to estimate the amount of extracorporeal circuit removal of calcium with regard to different dosages of regional citrate anticoagulation.

Citrate Supplementation Restores the Impaired Mineralisation Resulting from the Acidic Microenvironment: An In Vitro Study.

Chronic metabolic acidosis leads to bone-remodelling disorders based on excessive mineral matrix resorption and inhibition of bone formation, but also affects the homeostasis of citrate, which is an essential player in maintaining the acid-base balance and in driving the mineralisation process. This study aimed to investigate the impact of acidosis on the osteogenic properties of bone-forming cells and the effects of citrate supplementation in restoring the osteogenic features impaired by the acidic milieu. For this purpose, human mesenchymal stromal cells were cultured in an osteogenic medium and the extracellular matrix mineralisation was analysed at the micro- and nano-level, both in neutral and acidic conditions and after treatment with calcium citrate and potassium citrate. The acidic milieu significantly decreased the citrate release and hindered the organisation of the extracellular matrix, but the citrate supplementation increased collagen production and, particularly calcium citrate, promoted the mineralisation process. Moreover, the positive effect of citrate supplementation was observed also in the physiological microenvironment. This in vitro study proves that the mineral matrix organisation is influenced by citrate availability in the microenvironment surrounding bone-forming cells, thus providing a biological basis for using citrate-based supplements in the management of bone-remodelling disorders related to chronic low-grade acidosis.

Mumefural Improves Blood Flow in a Rat Model of FeCl3-Induced Arterial Thrombosis.

Mumefural (MF), a bioactive component of the processed fruit of Prunus mume Sieb. et Zucc, is known to inhibit platelet aggregation induced by agonists in vitro. In this study, we investigated the anti-thrombotic effects of MF using a rat model of FeCl3-induced arterial thrombosis. Sprague-Dawley rats were intraperitoneally injected with MF (0.1, 1, or 10 mg/kg) 30 min before 35% FeCl3 treatment to measure the time to occlusion using a laser Doppler flowmeter and to assess the weight of the blood vessels containing thrombus. MF treatment significantly improved blood flow by inhibiting occlusion and thrombus formation. MF also prevented collagen fiber damage in injured vessels and inhibited the expression of the platelet activation-related proteins P-selectin and E-selectin. Moreover, MF significantly reduced the increased inflammatory signal of nuclear factor (NF)-κB, toll-like receptor 4 (TLR4), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in blood vessels. After administration, MF was detected in the plasma samples of rats with a bioavailability of 36.95%. Therefore, we suggest that MF may improve blood flow as a candidate component in dietary supplements for improving blood flow and preventing blood circulation disorders.

Targeting Chemosensory Ion Channels in Peripheral Swallowing-Related Regions for the Management of Oropharyngeal Dysphagia.

Oropharyngeal dysphagia, or difficulty in swallowing, is a major health problem that can lead to serious complications, such as pulmonary aspiration, malnutrition, dehydration, and pneumonia. The current clinical management of oropharyngeal dysphagia mainly focuses on compensatory strategies and swallowing exercises/maneuvers; however, studies have suggested their limited effectiveness for recovering swallowing physiology and for promoting neuroplasticity in swallowing-related neuronal networks. Several new and innovative strategies based on neurostimulation in peripheral and cortical swallowing-related regions have been investigated, and appear promising for the management of oropharyngeal dysphagia. The peripheral chemical neurostimulation strategy is one of the innovative strategies, and targets chemosensory ion channels expressed in peripheral swallowing-related regions. A considerable number of animal and human studies, including randomized clinical trials in patients with oropharyngeal dysphagia, have reported improvements in the efficacy, safety, and physiology of swallowing using this strategy. There is also evidence that neuroplasticity is promoted in swallowing-related neuronal networks with this strategy. The targeting of chemosensory ion channels in peripheral swallowing-related regions may therefore be a promising pharmacological treatment strategy for the management of oropharyngeal dysphagia. In this review, we focus on this strategy, including its possible neurophysiological and molecular mechanisms.

Berberine inhibits cancer cells growth by suppressing fatty acid synthesis and biogenesis of extracellular vesicles.

AIMS: Berberine is an isoquinoline alkaloid extracted from the root, rhizome and stem bark of Coptidis Rhizoma. Previous studies have revealed the anti-tumor potential of berberine against various types of cancer cells. However, the underlying mechanisms are not yet fully understood. In this study, we focused on the effects of berberine on fatty acid synthesis and extracellular vesicles formation in cancer cells, and revealed the internal mechanism of berberine inhibition on cancer cell proliferation. MATERIALS AND METHODS: Anti-proliferative activity of berberine was determined by cell counting and microscope observation and cell cycle analysis. Activities of AMPK and ACC, expression of extracellular vesicles markers were detected by western blotting. 13C labeling metabolic flux analysis was used for determination of de novo synthesis of fatty acids. The excreted extracellular vesicles in culture mediums were separated by both polyethylene glycol enrichment of extracellular vesicles and differential centrifugation separation. KEY FINDINGS: Among our early experiments, 5-10 µmol/L berberine exhibited the substantial anti-proliferative effect against human colon cancer cell line HCT116, cervical cancer cell line HeLa and other cancer cells. It was also revealed that, through activating AMPK, berberine inhibited ACC activity then suppressed intracellular fatty acid synthesis, finally decreased the biogenesis of extracellular vesicles. Moreover, supplement with citrate acid, palmitic acid, as well as exogenous extracellular vesicles, could rescue the inhibitory effect of berberine on cell proliferation, suggesting that inhibited ACC activity, suppressed fatty acid synthesis and decreased extracellular vesicles production were important mechanisms account for berberine inhibiting cancer cell proliferation. SIGNIFICANCE: Our study indicates that berberine suppresses cancer cell proliferation through inhibiting the synthesis of fatty acids and decreasing biogenesis and secretion of extracellular vesicles, suggests that berberine is a promising candidate for the development of new therapies for cancer.

Effect of Citric Acid on Growth, Ecophysiology, Chloroplast Ultrastructure, and Phytoremediation Potential of Jute (Corchorus capsularis L.) Seedlings Exposed to Copper Stress.

Soil and water contamination from heavy metals and metalloids is one of the most discussed and caused adverse effects on food safety and marketability, crop growth due to phytotoxicity, and environmental health of soil organisms. A hydroponic investigation was executed to evaluate the influence of citric acid (CA) on copper (Cu) phytoextraction potential of jute (Corchorus capsularis L.). Three-weeks-old seedlings of C. capsularis were exposed to different Cu concentrations (0, 50, and 100 µM) with or without the application of CA (2 mM) in a nutrient growth medium. The results revealed that exposure of various levels of Cu by 50 and 100 µM significantly (p < 0.05) reduced plant growth, biomass, chlorophyll contents, gaseous exchange attributes, and damaged ultra-structure of chloroplast in C. capsularis seedlings. Furthermore, Cu toxicity also enhanced the production of malondialdehyde (MDA) which indicated the Cu-induced oxidative damage in the leaves of C. capsularis seedlings. Increasing the level of Cu in the nutrient solution significantly increased Cu uptake by the roots and shoots of C. capsularis seedlings. The application of CA into the nutrient medium significantly alleviated Cu phytotoxicity effects on C. capsularis seedlings as seen by plant growth and biomass, chlorophyll contents, gaseous exchange attributes, and ultra-structure of chloroplast. Moreover, CA supplementation also alleviated Cu-induced oxidative stress by reducing the contents of MDA. In addition, application of CA is helpful in increasing phytoremediation potential of the plant by increasing Cu concentration in the roots and shoots of the plants which is manifested by increasing the values of bioaccumulation (BAF) and translocation factors (TF) also. These observations depicted that application of CA could be a useful approach to assist Cu phytoextraction and stress tolerance against Cu in C. capsularis seedlings grown in Cu contaminated sites.