Increasing Natural Killer Cell Activity of Mineral Nanomaterial ALP1018 in Healthy Adults: A Randomized, Double-Blind, Placebo Comparative Clinical Trial.

This randomized, double-blind, placebo comparative clinical trial aimed to determine the immune-enhancing effects and safety of a nanomaterial with iron and zinc (ALP1018) in healthy adults. Participants who met the inclusion criteria were recruited for this study (n = 80) and randomly assigned to either the test group (n = 40), which was given Alp1018 in capsule form, or the placebo group (n = 40), which was given crystal cellulose capsules of identical appearance, weight, and flavor for 8 weeks. Compared to baseline, natural killer (NK) cell activity (%) increased in the test group after 8 weeks, although there were no changes in the placebo group. Furthermore, in the subgroup analysis of Coronavirus disease 2019 (COVID-19) affected participants, significantly increased NK cell activity was observed in the test group at 4 (p < 0.05) and 8 weeks (p < 0.05). No significant differences were observed in cytokine levels between the two groups. ALP1018 supplementation appeared to enhance immune function by improving NK cell activity without adverse effects in healthy adults.

Osteoblastgenic and Osteogenic Effects of KY-273 with CDK8/19 Inhibitory Activity in Bone Marrow Mesenchymal Stem Cells and Female Rats.

Osteoporosis is caused by imbalance between osteogenesis and bone resorption, thus, osteogenic drugs and resorption inhibitors are used for treatment of osteoporosis. The present study examined the effects of (R)-4-(1-hydroxyethyl)-3-{4-[2-(tetrahydropyran-4-yloxy)ethoxy]phenoxy}benzamide (KY-273), a diphenyl ether derivative, on CDK8/19 activity, osteoblast differentiation and femoral bone using micro-computed tomography in female rats. KY-273 potently inhibited CDK8/19 activity, promoted osteoblast differentiation with an increase in alkaline phosphatase (ALP) activity, and gene expression of type I collagen, ALP and BMP-4 in mesenchymal stem cells (ST2 cells). In female rat femur, ovariectomy decreased metaphyseal trabecular bone volume (Tb.BV), mineral content (Tb.BMC), yet had no effect on metaphyseal and diaphyseal cortical bone volume (Ct.BV), mineral content (Ct.BMC) and strength parameters (BSPs). In ovaries-intact and ovariectomized rats, oral administration of KY-273 (10 mg/kg/d) for 6 weeks increased metaphyseal and diaphyseal Ct.BV, Ct.BMC, and BSPs without affecting medullary volume (Med.V), but did not affect Tb.BV and Tb.BMC. In ovariectomized rats, alendronate (3 mg/kg/d) caused marked restoration of Tb.BV, Tb.BMC and structural parameters after ovariectomy, and increased metaphyseal but not diaphyseal Ct.BV, Ct.BMC, and BSPs. In ovaries-intact and ovariectomized rats, by the last week, KY-273 increased bone formation rate/bone surface at the periosteal but not the endocortical side. These findings indicate that KY-273 causes osteogenesis in cortical bone at the periosteal side without reducing Med.V. In conclusion, KY-273 has cortical-bone-selective osteogenic effects by osteoblastogenesis via CDK8/19 inhibition in ovaries-intact and ovariectomized rats, and is an orally active drug candidate for bone diseases such as osteoporosis in monotherapy and combination therapy.

Supplemental trace minerals as complexed or inorganic sources for beef cattle during the receiving period.

To investigate effects of inorganic or complexed trace mineral source (zinc, copper, manganese, and cobalt) on receiving period performance and morbidity, crossbred beef heifer calves (n = 287) arriving on three delivery dates were used in a 42-d receiving trial. Heifers were processed after arrival, stratified by day -1 body weights (BW) and allocated randomly to eight pens (11 to 13 heifers/pen, 24 pens total). Within truckload, pens were assigned randomly to dietary treatment (n = 12 pens/treatment). Heifers were housed on 0.42-ha grass paddocks, provided ad libitum bermudagrass hay and provided dietary treatments in grain supplements fed daily. Treatments consisted of supplemental zinc (360 mg/d), copper (125 mg/d), manganese (200 mg/d), and cobalt (12 mg/d) from complexed (Zinpro Availa 4, Zinpro Corp. Eden Prairie, MN) or inorganic sources (sulfates). Heifers were observed daily for clinical bovine respiratory disease (BRD). If presenting BRD symptoms and rectal temperature ≥ 40 °C, heifers were deemed morbid and treated with antibiotics. Six heifers/pen were bled to determine serum haptoglobin concentrations on days 0, 14, and 28. Liver biopsies were taken on day 5 ±â€…2 and 43 ±â€…1 from three calves selected randomly from each pen for mineral status comparisons. Statistical analyses were performed using the MIXED, GLIMMIX, and repeated measures procedures of SAS 9.4 with truckload as a random effect and pen within truckload specified as subject. There tended to be a treatment by day interaction for BW (P = 0.07). Heifer BW did not differ on day 0 (P = 0.82) and day 14 (P = 0.36), but heifers fed complexed trace minerals had greater BW on day 28 (P = 0.04) and day 42 (P = 0.05). Overall average daily gains were greater for heifers fed complexed trace minerals (P = 0.05; 0.78 vs. 0.70 kg, SE = 0.03). Heifers supplemented with inorganic trace minerals had greater BRD incidence (P = 0.03; 58 vs. 46%, SE = 3.6). Haptoglobin concentrations decreased throughout the trial (P < 0.001), and heifers fed complexed trace minerals tended to have a decrease in haptoglobin concentrations (P = 0.07). The source of trace mineral supplementation had no effect (P ≥ 0.20) on liver mineral concentrations and there were no treatment × day interactions (P ≥ 0.35). In conclusion, supplementing diets for the first 42 d after arrival with complexed trace mineral sources improved heifer performance as compared to heifers supplemented with inorganic trace minerals.

Issues associated with health and management of newly received cattle continue to pose significant animal welfare and economic challenges for the beef industry. Diagnosis of bovine respiratory disease, accompanied with poor growth performance, can be addressed by nutritional intervention in receiving cattle. Trace mineral inclusion in receiving rations is vital to calf performance. There are numerous sources of trace mineral supplements that exist commercially for cattle and their effects on immune function, growth, and performance measures were evaluated. Organic trace mineral supplements are being used in replacement of inorganic salts due to potentially greater bioavailability and functionality. An organic source that is commonly used are amino acid complexes. Replacing inorganic sources with complexed sources of trace minerals (zinc, copper, manganese, and cobalt) improved growth performance and decreased sickness during the 42-d receiving study.

Silicon Supplementation for Bone Health: An Umbrella Review Attempting to Translate from Animals to Humans.

Studies have attempted to demonstrate the benefits of silicon on bone health using a wide range of Si amounts-provided in the diet or through supplementation-and several different animal species. Previous studies in humans have also demonstrated a positive correlation between Si intake and bone health measures. The aim of the current review is to determine the effective levels of Si intake or supplementation that influence bone health to better inform future study designs and guidelines. Articles were identified using one of two search terms: "silicon AND bone" or "sodium zeolite A AND bone". Articles were included if the article was a controlled research study on the effect of Si on bone health and/or mineral metabolism and was in English. Articles were excluded if the article included human subjects, was in vitro, or studied silica grafts for bone injuries. Silicon type, group name, Si intake from diet, Si supplementation amount, animal, and age at the start were extracted when available. Dietary Si intake, Si supplementation amount, and the amount of Si standardized on a kg BW basis were calculated and presented as overall mean ± standard deviations, medians, minimums, and maximums. Studies that left out animal weights, amount of food or water consumed, or nutrient profiles of the basal diet were excluded from these calculations. Standardized Si intakes ranged from 0.003 to 863 mg/kg BW, at times vastly exceeding current human Si intake recommendations (25 mg/d). The lack of data provided by the literature made definitively determining an effective threshold of supplementation for skeletal health difficult. However, it appears that Si consistently positively influences bone and mineral metabolism by around 139 mg Si/kg BW/d, which is likely unfeasible to attain in humans and large animal species. Future studies should examine this proposed threshold more directly and standardize supplemental or dietary Si intakes to kg BW for better study replication and translation.

Insights into the effect of manganese-based nanomaterials on the distribution trait and nutrition of radish (Raphanus sativus L.).

Manganese (Mn) is one of the essential elements for plant growth and is involved in the process of photosynthesis and seed germination. Herein, we applied two Mn-based nanoparticles, MnO2 and Mn3O4, to the soil to investigate their effects on radish growth, antioxidant system, and nutrients. The radish plant height after treatment with 10 mg/kg of MnO2 and Mn3O4 NPs were increased, compare to the control. In radish's shoot, MnO2 NPs at high concentrations (100 mg/kg) increased MDA activity by 58 % compared to the control group, while exposure to Mn3O4 NPs at the same concentration decreased MDA activity by 14 %. The nutrient content of radishes, such as soluble sugar and vitamin C, was improved. Moreover, single particle inductively coupled plasma mass spectrometry (SP ICP-MS) was used to understand the patterns of migration of Mn-based NPs in radish and subsequent impact on nutrients. We found that Mn-based NPs accumulated mainly in the roots of radish. Interestingly, the accumulation characteristics of MnO2 NPs and Mn3O4 NPs were different. MnO2 NPs accumulated more in radish leaves than in fruits, while the accumulation of Mn3O4 NPs gradually decreased from roots to leaves. Finally, we determined the mineral element content of the leaves, fruits, and roots of radish, and found that the uptake of main metallic mineral elements (e.g. Cu, Fe, Mg, Zn, Na, K) was inhibited by the application of Mn-based NPs. These findings underscore the importance of considering species and multifaceted impacts of Mn-based NPs as nanofertilizers for their wide application in agriculture.

Organic fertilizer type and dose affect growth, morphological and physiological parameters, and mineral nutrition of watermelon seedlings.

Background: Organic agriculture has grown rapidly in recent years due to its environmental friendliness, sustainability, and improved farm profitability. Transplants are commonly used for fruits and vegetables to achieve consistent quality, uniformity, and easy field spacing control. The efficacy and optimal amounts of fertilizers for organic transplant production need to be investigated. Methods: The effects of three organic fertilizers (Sustane 4-6-4, Nature Safe 7-7-7, and Dramatic 2-4-1) and one conventional fertilizer Peters Professional 20-20-20 (Conventional) with four doses (nitrogen (N) content was matched among fertilizers in each level, as 0.14 g/L, 0.28 g/L, 0.56 g/L, and 0.84 g/L N, respectively) on watermelon seedlings were compared in this study. Results: The results showed that all organic fertilizer treatments were not significantly different from the Conventional group in terms of watermelon germination. The only exception was the highest dose of Sustane 4-6-4 (0.84 g/L N) which decreased the germination rate and relative emergence index. Generally, growth index, shoot fresh and dry weights, true leaf number, and stem diameter increased as the amount of N increased within each fertilizer type. The best shoot growth was observed in the highest doses of Conventional and Dramatic 2-4-1 treatments (0.84 g/L N). However, Dramatic 2-4-1 treatments resulted in the lowest root growth when compared to other fertilizers at the same N dose. The second highest fertilization dose (0.56 g/L N) of Sustane 4-6-4 had the best root growth according to root fresh weight, root volume, root area, total root length, as well as the numbers of root tip and crossing when compared to other treatments. For seedlings, a well-developed root system can ensure a good seedling establishment and high survival rate under stressful field conditions after transplanting. Thus, Sustane 4-6-4 at 14 g/L (0.56 g/L N) is recommended to produce high-quality organic watermelon seedlings among the treatments applied in this study.

Do dietary interventions exert clinically important effects on the bioavailability of ß-lactam antibiotics? A systematic review with meta-analyses.

BACKGROUND: Managing drug-food interactions may help to achieve the optimal action and safety profile of ß-lactam antibiotics. METHODS: We conducted a systematic review with meta-analyses in adherence to PRISMA guidelines for 32 ß-lactams. We included 166 studies assessing the impact of food, beverages, antacids or mineral supplements on the pharmacokinetic (PK) parameters or PK/pharmacodynamic (PK/PD) indices. RESULTS: Eighteen of 25 ß-lactams for which data on food impact were available had clinically important interactions. We observed the highest negative influence of food (AUC or Cmax decreased by >40%) for ampicillin, cefaclor (immediate-release formulations), cefroxadine, cefradine, cloxacillin, oxacillin, penicillin V (liquid formulations and tablets) and sultamicillin, whereas the highest positive influence (AUC or Cmax increased by >45%) for cefditoren pivoxil, cefuroxime and tebipenem pivoxil (extended-release tablets). Significantly lower bioavailability in the presence of antacids or mineral supplements occurred for 4 of 13 analysed ß-lactams, with the highest negative impact for cefdinir (with iron salts) and moderate for cefpodoxime proxetil (with antacids). Data on beverage impact were limited to 11 antibiotics. With milk, the extent of absorption was decreased by >40% for cefalexin, cefradine, penicillin G and penicillin V, whereas it was moderately increased for cefuroxime. No significant interaction occurred with cranberry juice for two tested drugs (amoxicillin and cefaclor). CONCLUSIONS: Factors such as physicochemical features of antibiotics, drug formulation, type of intervention, and patient's health state may influence interactions. Due to the poor actuality and diverse methodology of included studies and unproportionate data availability for individual drugs, we judged the quality of evidence as low.

The role of calcium in the prevention of erosive tooth wear: a systematic review and meta-analysis.

OBJECTIVES: The loss of hard dental tissue due to recurrent acid challenges and mechanical stresses without bacterial involvement is known as erosive tooth wear (ETW). Many studies in the literature have concentrated on variables that may affect the ETW process and prevent its occurrence or reduce its advancement. However, to date, no previous systematic review has evaluated the role of calcium in preventing ETW. Therefore, the purpose of the present systematic review was to review and critically appraise the scientific evidence regarding the role of calcium formulations in the prevention of ETW. METHODS: The review protocol was registered in the PROSPERO international prospective register of systematic reviews (Ref: CRD42021229819). A literature search was conducted in electronic databases to identify in situ randomized controlled trials evaluating the prevention of ETW following the application of calcium formulations. The outcomes studied included mean enamel loss, surface microhardness, surface roughness, mean erosion/softening depth, mineral loss/precipitation and remineralization. Study characteristics and outcomes of included studies were summarized. Cochrane's risk-of-bias tool 2.0 was used to assess the quality of eligible studies, and meta-analysis using a random effects model was performed. RESULTS: The search retrieved 869 studies of which 21 were considered eligible. Regarding the results of the quality assessment for potential risk of bias in all included studies, overall, 5 studies were considered as being at low risk, another 12 at unclear risk and 4 at high risk of bias. The findings of the studies showed that the addition of calcium in juice drinks led to reduced enamel loss, with blackcurrant juice presenting 2.6 times statistically significant less enamel loss compared to orange juice (p = 0.0001, I2 = 89%). No statistically significant difference in mean surface microhardness of eroded enamel was recorded between chewing gum with or without casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) (p = 0.31, I2 = 71%). Contradictory were the results regarding the effect of milk and CPP-ACP pastes on prevention of ETW. CONCLUSIONS: Calcium formulations play an important role in ETW prevention, mainly through their addition to acidic drinks.

Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial and meta-analysis of 3 cognitive studies within COSMOS.

BACKGROUND: Longer effects of multivitamin-mineral (MVM) supplementation on late-life cognitive function remain untested using in-person, detailed neuropsychological assessments. Furthermore, insufficient evidence exists for healthcare providers to recommend daily MVM supplements to prevent cognitive decline. OBJECTIVES: This study aimed to test MVM effects on cognitive change using in-person, detailed neuropsychological assessments and conduct a meta-analysis within COSMOS (COcoa Supplement and Multivitamin Outcomes Study) cognitive substudies for a robust evaluation of MVM effects on cognition. METHODS: COSMOS is a 2 × 2 factorial trial of cocoa extract (500 mg flavanols/d) and/or a daily MVM supplement for cardiovascular disease and cancer prevention among 21,442 United States adults aged ≥60 y. There were 573 participants in the clinic subcohort of COSMOS (that is, COSMOS-Clinic) who completed all cognitive tests administered at baseline. For the meta-analysis, we included nonoverlapping participants across 3 COSMOS cognitive substudies: COSMOS-Clinic (n = 573); COSMOS-Mind (n = 2158); COSMOS-Web (n = 2472). RESULTS: In COSMOS-Clinic, we observed a modest benefit of MVM compared with placebo on global cognition over 2 y {mean difference [95% confidence interval (CI)] = 0.06 SD units (SU) (-0.003, 0.13)}, with a significantly more favorable change in episodic memory [mean difference (95% CI) = 0.12 SU (0.002, 0.23)] but not in executive function or attention [mean difference (95% CI) = 0.04 SU (-0.04, 0.11)]. The meta-analysis of COSMOS substudies showed clear evidence of MVM benefits on global cognition [mean difference (95% CI) = 0.07 SU (0.03, 0.11); P = 0.0009] and episodic memory [mean difference (95% CI) = 0.06 SU (0.03, 0.10); P = 0.0007]; the magnitude of effect on global cognition was equivalent to reducing cognitive aging by 2 y. CONCLUSIONS: In COSMOS-Clinic, daily MVM supplementation leads to a significantly more favorable 2-y change in episodic memory. The meta-analysis within COSMOS cognitive substudies indicates that daily MVM significantly benefits both global cognition and episodic memory. These findings within the COSMOS trial support the benefits of a daily MVM in preventing cognitive decline among older adults. This trial was registered at COSMOS-clinicaltrials.gov as NCT02422745, at COSMOS-Mind-clinicaltrials.gov as NCT03035201, and at COSMOS-Web-clinicaltrials.gov as NCT04582617.

The application of synthetic antibacterial minerals to combat topical infections: exploring a mouse model of MRSA infection.

The development of new antibiotics has stalled, and novel strategies are needed as we enter the age of antibiotic resistance. Certain naturally occurring clays have been shown to be effective in killing antibiotic resistant bacteria. However, these natural clays are too variable to be used in clinical settings. Our study shows that synthetic antibacterial minerals exhibit potent antibacterial activity against topical MRSA infections and increase the rate of wound closure relative to controls. The antibacterial minerals maintain a redox cycle between Fe2+/Fe3+ and the surfaces of pyrite minerals, which act as a semiconductor and produce reactive oxygen species (ROS), while smectite minerals act as a cation exchange reservoir. Acidic conditions are maintained throughout the application of the hydrated minerals and can mitigate the alkaline pH conditions observed in chronic non-healing wounds. These results provide evidence for the strategy of 'iron overload' to combat antibiotic resistant infections through the maintained release of Fe2+ and generation of ROS via distinct geochemical reactions that can break the chronic wound damage cycle.

UPLC-Q-TOF-MS profiling of Viola stocksii Boiss. and evaluation of aphrodisiac potential and risk factors associated with erectile dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Viola stocksii Boiss. locally known as makhni or makhanr booti, is an important medicinal food plant with multiple therapeutic applications, including erectile dysfunction (ED). It is mixed with butter and used for boosting energy and sexual health in the subcontinent. AIMS OF THE STUDY: This study was designed to evaluate the chemical composition, aphrodisiac potential and effect of V. stocksii on the risk factors associated with ED. METHODOLOGY: The hydroethanolic extract of V. stocksii (HEEVS) was prepared through the microwave-assisted extraction (MAE) technique. The chemical composition was evaluated using preliminary phytochemical screening and UPLC-Q-TOF-MS analysis. Metals and minerals analysis was performed by an atomic absorption spectrophotometer. The aphrodisiac activity of HEEVS was evaluated using an in vivo aphrodisiac model established in male albino rats and the effect on various sexual parameters such as mount, intromission, ejaculation frequencies and mount, intromission, ejaculation latencies, postejaculatory interval, penile reflexes and serum hormone concentration were analyzed. The effect of HEEVS on various risk factors associated with ED, including prostate cancer (PC), bacterial infections, diabetes and obesity, was evaluated using various in vitro assays. Moreover, four compounds were selected from the UPLC-Q-TOF-MS profile and evaluated for in silico computational analysis against phosphodiesterase-5 (PDE-5) for possible interaction. FINDINGS: The phytochemical screening revealed the presence of various secondary metabolites in HEEVS, while 58 compounds were tentatively identified in the UPLC-Q-TOF-MS analysis. Various important minerals and metals such as zinc, calcium, cadmium and magnesium were detected in the atomic absorption spectrometry analysis. The in vivo aphrodisiac evaluation showed a significant (p < 0.05) increase in the mount, intromission and ejaculation frequencies and a decrease in the mount, intromission latencies and post-ejaculatory intervals at a dose of 300 mg/kg. A marked (p < 0.05) increase was observed in the concentration of serum testosterone and luteinizing hormones in HEEVS treated animals with a significant increase in total penile reflexes. The extract displayed significant anti-prostate cancer activity and a potential antibacterial spectrum against E. coli and S. aureus, with MIC50 values of 215.72 µg/mL and 139.05 µg/mL, respectively. Similarly, HEEVS was found active towards pancreatic lipase (67.34 ± 1.03%), α-glucosidase (3.87 ± 0.54 mmol ACAE/g d.w.) and α-amylase (6.98 ± 1.63 mmol ACAE/g d.w.). The in silico docking study presented a potential interaction between the selected compounds and residues of the active site of PDE-5. CONCLUSION: This report highlights the aphrodisiac potential of V. stocksii and provides experimental support for its traditional use in ED with an attenuative effect on the risk factors associated with ED. Moreover, the chemical composition displayed the presence of functional phytoconstituents and minerals in HEEVS and paves the way for the isolation of compounds with potent aphrodisiac activity.

Deciphering the effect of salinity and boron stress on broccoli plants reveals that membranes phytosterols and PIP aquaporins facilitate stress adaptation.

Abiotic stresses, such as salinity and boron toxicity/deficiency, are prevalent in arid and semi-arid regions where broccoli is largely cultivated. This study aimed to investigate the physiological response of broccoli leaves to these stresses, focusing on parameters such as growth, relative water content, stomatal conductance, and mineral concentration after 15 days of treatment application. The effects of individual and combined stresses of salinity and boron (deficiency and toxicity) were examined. Additionally, the study explored the molecular aspects of PIP aquaporins in relation to their presence in the plasma membrane and their interaction with the lipid environment. The results showed that the combined stress of salinity and boron deficiency resulted in a significant reduction in plant biomass, suggesting a specific adaptation to this stress combination. Changes in stomatal conductance and mineral nutrient levels indicated that the adaptation mechanisms were associated with water and boron concentration in the leaves. The expression patterns of PIP aquaporins varied among the different stress treatments, either individually or in combination. Furthermore, the presence of aquaporins in the plasma membrane and microsomal fraction highlighted the potential regulatory roles of trafficking along with the membrane composition, particularly the concentration of phytosterols. The results underscore the importance of water transport by aquaporins and their interaction with the sterol composition in the membranes, in facilitating salinity-boron stress adaptation mechanisms.

Building a highly efficient Streptomyces super-chassis for secondary metabolite production by reprogramming naturally-evolved multifaceted shifts.

Streptomyces has an extensive array of bioactive secondary metabolites (SMs). Nevertheless, devising a framework for the heterologous production of these SMs remains challenging. We here reprogrammed a versatile plug-and-play Streptomyces super-chassis and established a universal pipeline for production of diverse SMs via understanding of the inherent pleiotropic effects of ethanol shock on jadomycin production in Streptomyces venezuelae. We initially identified and characterized a set of multiplex targets (afsQ1, bldD, bldA, and miaA) that contribute to SM (jadomycin) production when subjected to ethanol shock. Subsequently, we developed an ethanol-induced orthogonal amplification system (EOAS), enabling dynamic and precise control over targets. Ultimately, we integrated these multiplex targets into functional units governed by the EOAS, generating a universal and plug-and-play Streptomyces super-chassis. In addition to achieving the unprecedented titer and yield of jadomycin B, we also evidenced the potential of this super-chassis for production of diverse heterologous SMs, including antibiotic oxytetracycline, anticancer drug doxorubicins, agricultural herbicide thaxtomin A, and plant growth regulator guvermectin, all with the yields of >10 mg/g glucose in a simple mineral medium. Given that the production of SMs all required complexed medium and the cognate yields were usually much lower, our achievement of using a universal super-chassis and engineering pipeline in a simple mineral medium is promising for convenient heterologous production of SMs.

Role of MAPKs in TGF-ß1-induced maturation and mineralization in human osteoblast-like cells.

OBJECTIVES: Our study aimed to clarify the role of mitogen-activated protein kinases (MAPKs) in transforming growth factor (TGF)-ß1-stimulated mineralization in the human osteoblast-like MG63 cells. METHODS: The viability of MG63 cells under TGF-ß1 stimulation was assessed by MTS assay. Western blotting determined TGF-ß1-mediated activation of extracellular signal-related protein kinase (ERK), p38, and c-Jun amino-terminal kinase (JNK). Mineralization-related gene expression was examined by quantitative real-time PCR, and mineral deposition levels were evaluated by alizarin red S staining. RESULTS: TGF-ß1 had no effect on MG63 cell proliferation. Activation of p38 was observed at 3 h post TGF-ß1 stimulation. Moreover, JNK phosphorylation was upregulated by TGF-ß1 from 1 to 6 h post stimulation, but had no activation on ERK phosphorylation throughout the experimental period. Treatment with JNK inhibitor diminished the alizarin red S-stained area in a dose-dependent manner. Mineral deposition was unaffected by MEK inhibitor, whereas p38 inhibitor increased the red-stained area. Gene expression levels of ALP and BSP were significantly decreased under treatment with JNK inhibitor and p38 inhibitor. The MEK inhibitor had no effect on the TGF-ß1-mediated upregulation of ALP and BSP. Although all three inhibitors suppressed expression of COL I, none were found to stimulate expression of OCN. CONCLUSIONS: Human osteoblast-like MG63 cells maturation and mineralization are induced through JNK activation of MAPK signaling in response to TGF-ß1.

Comparative Evaluation of the Effect of Different Chelating Agents on Mineral Content and Erosion of Radicular Dentine: A FESEM-EDS Analysis.

OBJECTIVE: Irrigating solutions play an important role in the debridement and disinfection of the root canal space, and thus, it is crucial to comprehend their effects on the composition and surface structure of radicular dentine. This study evaluated and compared the effects of 17% ethylenediaminetetraacetic acid (EDTA), 9% 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) and 0.2% chitosan on the mineral content and erosion of radicular dentine when used as a final rinse. METHODS: Sixty extracted human mandibular premolar teeth were decoronated and instrumented to ProTaper size F2. After final instrumentation, the samples were randomly divided into 4 groups (n=15) according to the type of final irrigant used: Normal saline (control), 17% EDTA, 9% HEBP and 0.2% chitosan. Field emission scanning electron microscopy was used to assess the erosion of radicular dentine, and energy dispersive X- ray spectroscopy was used to quantify the radicular dentine mineral composition at the coronal, middle and apical levels of all the prepared samples after final irrigation. The one-way analysis of variance was used for intra-group and inter-group comparisons of means, the Kruskal Wallis test for intra-group and inter-group comparisons of medians and Tukey's post hoc test for pairwise comparisons. RESULTS: There was no significant difference in the levels of calcium (Ca), phosphorus (P) and Ca/P ratio after final rinse with 17% EDTA, 9% HEBP and 0.2% chitosan at all three root levels (p>0.05); except at the coronal level, where 0.2% chitosan caused significantly less alteration in Ca levels and Ca/P ratio than 17% EDTA and 9% HEBP respectively (p<0.05). 17% EDTA, 9% HEBP and 0.2% chitosan caused no erosion at the middle and apical levels. Meanwhile, 17% EDTA and 9% HEBP caused moderate erosion at the coronal level. CONCLUSION: Alternatives to 17% EDTA during final irrigation can be 9% HEBP and 0.2% chitosan. (EEJ-2023-06-078).

Influence of the Salivary Acquired Pellicle on the Inhibition/Progression of In Vitro Carious Dentin Treated with Silver Diamine Fluoride.

Purpose: To evaluate, in vitro, whether the presence of the acquired pellicle (AP) interferes with the effect of 38 percent silver diamine fluoride (SDF) on the inhibition or progression of carious dentin. Methods: Carious dentin specimens were divided into groups: C-no treatment control; FV-fluoride varnish; AP-acquired pellicle formation; SDF only, and APSDF-SDF plus acquired pellicle formation. After AP formation (AP and APSDF groups), all groups were subjected to pH cycling. Dentin mineral gain or loss was quantified using surface microhardness (SM). Concentrations of fluoride calcium (CaF2) and fluorapatite (FAp) fluoride retained in dentin and fluoride concentrations in de- and remineralizing solutions were determined. Results: Groups AP, FV, SDF, and APSDF showed reduced demineralization compared with the C group, but the AP group showed greater surface loss than the fluoridated groups. Groups FV, SDF, and APSDF showed greater mineral recovery than C and AP groups (P<0.05), but no differences were observed between the FV, SDF, and APSDF groups (P>0.05). The retained CaF2 and FAp were greater in the groups treated with fluoride, but there was no difference between the SDF and APSDF groups. Conclusion: The presence of the acquired pellicle reduced the progression of carious dentin lesion but did not influence its remineralization when associated with silver diamine fluoride.

Supplementing dairy feed by dicalcium phosphate and effect on dry matter intake, digestibility, milk composition, and blood mineral balances in crossbred dairy cows.

The present study was conducted to assess if Dicalcium Phosphate 18% (DCP) supplementation in dairy feed would affect dry matter intake, milk composition, blood mineral balance and milk production in lactating crossbred Dairy Cows). A 4 × 4 double change-over design set as Latin Squares was used to do feeding and digestibility trials. DCP was supplemented at different levels 0; 0.3; 0.6; 0.9% DM/day of DCP for which the experimental groups was respectively designated as T0, T1, T2, T3, The effect of DCP supplementation on parameters of interest was evaluated using blood serum, milk, feed and feed refusals samples. The present study revealed that supplementation of DCP with the concentrate mix improved mean dry matter intake (11.46; 12.81; 14.59, and 15.68 kg DM/d) for T0, T1, T2, T3, respectively, and digestibility of nutrients in lactating dairy cows compared to the controls. Likewise, DCP supplementation improved milk production and composition except solids not fat (SNF) composition. Serum calcium (Ca) composition was significantly in supplemented group (p<0.05). DCP supplementation significantly improved (p<0.05) total Ca intake, Ca in milk, Ca in feces, total Ca excretion. Optimum dairy cow production and productivity was achieved at 0.6% DM/day of DCP supplementation. However, the current results need to be confirmed using large number of lactating dairy animals.

Exogenous γ-aminobutyric acid improves the photosynthesis efficiency, soluble sugar contents, and mineral nutrients in pomegranate plants exposed to drought, salinity, and drought-salinity stresses.

BACKGROUND: γ-aminobutyric acid (GABA), as a regulator of many aspects of plant growth, has a pivotal role in improving plant stress resistance. However, few studies have focused on the use of GABA in increasing plants' resistance to interactional stresses, such as drought-salinity. Therefore, the focus of this study was to examine the effect of foliar application of GABA (0, 10, 20, and 40 mM) on growth indices and physio-biochemical parameters in plants of two pomegranate cultivars, 'Rabab' and 'Atabaki' exposed to drought, salinity, and drought-salinity. RESULTS: Under stress conditions, the photosynthetic capacity of two pomegranate cultivars, including transpiration rate, net photosynthetic rate, intercellular carbon dioxide concentration, stomatal conductance of water vapour, and mesophyll conductance, was significantly reduced. This resulted in a decrease in root morphological traits such as fresh and dry weight, diameter, and volume, as well as the fresh and dry weight of the aerial part of the plants. However, the application of GABA reversed the negative effects caused by stress treatments on growth parameters and maintained the photosynthetic capacity. GABA application has induced the accumulation of compatible osmolytes, including total soluble carbohydrate, starch, glucose, fructose, and sucrose, in charge of providing energy for cellular defense response against abiotic stresses. Analysis of mineral nutrients has shown that GABA application increases the absorption of potassium, potassium/sodium, magnesium, phosphorus, manganese, zinc, and iron. As concentration increased up to 40 mM, GABA prevented the uptake of toxic ions, sodium and chloride. CONCLUSIONS: These findings highlight the potential of GABA as a biostimulant strategy to enhance plant stress tolerance.

Vitamins and Minerals for Blood Pressure Reduction in the General, Normotensive Population: A Systematic Review and Meta-Analysis of Six Supplements.

Hypertension is the leading preventable risk factor for cardiovascular disease and all-cause mortality worldwide. However, studies have shown increased risk of mortality from heart disease and stroke even within the normal blood pressure (BP) range, starting at BPs above 110-115/70-75 mm Hg. Nutraceuticals, such as vitamins and minerals, have been studied extensively for their efficacy in lowering BP and may be of benefit to the general, normotensive population in achieving optimal BP. Our study investigated the effects of six nutraceuticals (Vitamins: C, D, E; Minerals: Calcium, Magnesium, Potassium) on both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in this population. We performed a systematic review and pairwise meta-analysis for all six supplements versus placebo. Calcium and magnesium achieved significant reductions in both SBP and DBP of -1.37/-1.63 mm Hg and -2.79/-1.56 mm Hg, respectively. Vitamin E and potassium only yielded significant reductions in SBP with values of -1.76 mm Hg and -2.10 mm Hg, respectively. Vitamins C and D were not found to significantly lower either SBP or DBP. Future studies should determine optimal dosage and treatment length for these supplements in the general, normotensive population.

Evaluation of alveolar ridge preservation in sockets with buccal dehiscence defects using two types of xenogeneic biomaterials: An in vivo experimental study.

OBJECTIVES: Alveolar ridge preservation (ARP) has been extensively investigated in various preclinical and clinical studies, yielding favorable results. We aim to evaluate the effects of ARP using collagenated bovine bone mineral (CBBM) alone or particulated bovine bone mineral with a non-cross-linked collagen membrane (PBBM/NCLM) in tooth extraction sockets with buccal dehiscence in an experimental dog model. MATERIALS AND METHODS: The mesial roots of three mandibular premolars (P2, P3, and P4) were extracted from six mongrel dogs 4 weeks after inducing dehiscence defects. ARP was randomly performed using two different protocols: 1) CBBM alone and 2) PBBM/NCLM. Three-dimensional (3D) volumetric, micro-computed tomography, and histological analyses were employed to determine changes over a span of 20 weeks. RESULTS: In 3D volumetric and radiographic analyses, CBBM alone demonstrated similar effectiveness to PBBM/NCLM in ARP (p > .05). However, in the PBBM/NCLM group (3.05 ± 0.60 mm), the horizontal ridge width was well maintained 3 mm below the alveolar crest compared with the CBBM group (2.11 ± 1.01 mm, p = .002). CONCLUSION: Although the radiographic changes in the quality and quantity of bone were not significant between the two groups, the use of PBBM/NCLM resulted in greater horizontal dimensions and more favorable maintenance of the ridge profile.