optimal dose
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Author(s):  
Md. Mashiar Rahman ◽  
Md. Abdullah Al Noman ◽  
Md. Walid Hossain ◽  
Rahat Alam ◽  
Selena Akter ◽  
...  

AbstractLoss of tubulin is associated with neurodegeneration and brain aging. Turmeric (Curcuma longa L.) has frequently been employed as a spice in curry and traditional medications in the Indian subcontinent to attain longevity and better cognitive performance. We aimed to evaluate the unelucidated mechanism of how turmeric protects the brain to be an anti-aging agent. D. melanogaster was cultured on a regular diet and turmeric-supplemented diet. β-tubulin level and physiological traits including survivability, locomotor activity, fertility, tolerance to oxidative stress, and eye health were analyzed. Turmeric showed a hormetic effect, and 0.5% turmeric was the optimal dose in preventing aging. β-tubulin protein level was decreased in the brain of D. melanogaster upon aging, while a 0.5% turmeric-supplemented diet predominantly prevented this aging-induced loss of β-tubulin and degeneration of physiological traits as well as improved β-tubulin synthesis in the brain of D. melanogaster early to mid-age. The higher concentration (≥ 1%) of turmeric-supplemented diet decreased the β-tubulin level and degenerated many of the physiological traits of D. melanogaster. The turmeric concentration-dependent increase and decrease of β-tubulin level were consistent with the increment and decrement data obtained from the evaluated physiological traits. This correlation demonstrated that turmeric targets β-tubulin and has both beneficial and detrimental effects that depend on the concentration of turmeric. The findings of this study concluded that an optimal dosage of turmeric could maintain a healthy neuron and thus healthy aging, by preventing the loss and increasing the level of β-tubulin in the brain.


2022 ◽  
Author(s):  
Kun Han ◽  
Nan Kang ◽  
Xiaotong Yu ◽  
Jie Lu ◽  
Yuewen Ma

Abstract In previous studies, we found radial extracorporeal shock wave (rESW), can promote the proliferation of neural stem cells(NSCs). Emerging evidence suggests that lncRNA NEAT1 can regulate NSCs proliferation. Whether lncRNA NEAT1 plays a role in the proliferation of NSC induced by shock waves is unclear. Cell Counting Kit-8(CCK 8) method was used to detect the proliferation of NSCs, and the relative protein and mRNA expression of related genes of Nestin, Cyclin D1 and P21 were detected by Western Blot and Quantitative real-time PCR(RT-qPCR)respectively. Immunofluorescence staining was used to observe the changes in the number of BrdU/nestin positive cells. Overexpression of NEAT1 and let 7b in cells were used to explore whether rESW can rescue the decreased number of NSCs.We found that the optimal dose of R15 transmitter promoting NSCs proliferation is 1.5 bar, 500 pulse, 2 Hz. 1.2-1.5bar showed a dose-dependent effect on the proliferation of NSCs, but it was negatively correlated with the proliferation effect of NSC when it was more than 1.5bar. We revealed that let 7b-P21 axis was involved in regulating the inhibition of NSC proliferation which was activated by NEAT1 in NSCs. In addition, we demonstrated that rESW treatment resulted in the decrease of NEAT1 expression, which was accompanied by the improved biological function including proliferation.Our results confirm that low-intensity rESW(1.5bar,500pulse,2Hz) can promote the proliferation of NSCs through NEAT1-let 7b-P21 axis.


2022 ◽  
Author(s):  
Ashleigh Tuite ◽  
Nelson Lee ◽  
David Fisman

Background: Provision of safe and effective vaccines has been a remarkable public health achievement during the SARS-CoV-2 pandemic. The effectiveness and durability of protection of the first two doses of SARS-CoV-2 vaccines is an important area for study, as are questions related to optimal dose combinations and dosing intervals. Methods: We performed a case-cohort study to generate real-world evidence on efficacy of first and second dose of SARS-CoV-2 vaccines, using a population-based case line list and vaccination database for the province of Ontario, Canada between December 2020 and October 2021. Risk of infection after vaccination was evaluated in all laboratory-confirmed vaccinated SARS-CoV-2 cases, and a 2% sample of vaccinated controls, evaluated using survival analytic methods, including construction of Cox proportional hazards models. Vaccination status was treated as a time-varying covariate. Results: First and second doses of SARS-CoV-2 vaccine markedly reduced risk of infection (first dose efficacy 68%, 95% CI 67% to 69%; second dose efficacy 88%, 95% CI 87 to 88%). In multivariable models, extended dosing intervals were associated with lowest risk of breakthrough infection (HR for redosing 0.64 (95% CI 0.61 to 0.67) at 6-8 weeks). Heterologous vaccine schedules that mixed viral vector vaccine first doses with mRNA second doses were significantly more effective than mRNA only vaccines. Risk of infection largely vanished during the time period 4-6 months after the second vaccine dose, but rose markedly thereafter. Interpretation: A case-cohort design provided an efficient means to identify strong protective effects associated with SARS-CoV-2 vaccination, particularly after the second dose of vaccine. However, this effect appeared to wane once more than 6 months had elapsed since vaccination. Heterologous vaccination and extended dosing intervals improved the durability of immune response.


2022 ◽  
Vol 12 ◽  
Author(s):  
Won-Ho Kang ◽  
Hyo-Jeong Ryu ◽  
Seongsung Kwak ◽  
Hwi-Yeol Yun

In recent, Botulinum Neurotoxin A1 (BoNT/A1) has been suggested as a potential anticancer agent due to neuronal innervation in tumor cells. Although potential BoNT/A1’s mechanism of action for the tumor suppression has been gradually revealed so far, there were no reports to figure out the exposure-response relationships because of the difficulty of its quantitation in the biological matrix. The main objectives of this study were to measure the anticancer effect of BoNT/A1 using a syngeneic mouse model transplanted with melanoma cells (B16-F10) and developed a kinetic-pharmacodynamic (K-PD) model for quantitative exposure-response evaluation. To overcome the lack of exposure information, the K-PD model was implemented by the virtual pharmacokinetic compartment link to the pharmacodynamic compartment of Simeoni’s tumor growth inhibition model and evaluated using curve-fitting for the tumor growth-time profile after intratumoral injection of BoNT/A1. The final K-PD model was adequately explained for a pattern of tumor growth depending on represented exposure parameters and simulation studies were conducted to determine the optimal dose under various scenarios considering dose strength and frequency. The optimal dose range and regimen of ≥13.8 units kg−1 once a week or once every 3 days was predicted using the final model in B16-F10 syngeneic model and it was demonstrated with an extra in-vivo experiment. In conclusion, the K-PD model of BoNT/A1 was well developed to optimize the dosing regimen for evaluation of anticancer effect and this approach could be expandable to figure out quantitative interpretation of BoNT/A1’s efficacy in various xenograft and/or syngeneic models.


2022 ◽  
Vol 66 (9-10) ◽  
pp. 30-38
Author(s):  
N. M. Krasnova ◽  
S. G. Efremenko ◽  
N. E. Evdokimova ◽  
O. I. Filippova ◽  
Y. V. Chertovskikh ◽  
...  

Background. Individual sensitivity to isoniazid in tuberculosis patients is determined by the presence of N-acetyltransferase 2 (NAT2) enzyme gene allelic variants in genome. Evaluation of quantitative and qualitative alterations in peripheral blood can be used for diagnosis, disease severity estimation, or as a clue for estimation of anti-tuberculosis chemotherapy effectiveness and safety.Aim: Find associations between acetylation type and peripheral red blood cell (RBC) dynamics; determine the effect of NAT2 acetylation rate on the effectiveness and safety of treatment in patients with newly identified pulmonary tuberculosis (TB) residing in the Sakha Republic (Yakutia).Methods. This study included 146 patients with various clinical forms of newly diagnosed pulmonary TB. Oral isoniazid, rifampicin, pyrazinamide, and ethambutol were administered patients. Genotyping was performed via real time PCR.Results. Rapid and intermediate acetylators showed an increase in hemoglobin concentrations and RBC erythrocyte hemoglobin content by the end of chemotherapy (P<0.05). Incidence of anemia was lower in intermediate acetylators, compared to rapid or slow acetylators (P=0.013). Negative correlation was established between absolute RBC count and slow acetylation type (P=0.017). Patients with rapid acetylation type showed increased RBC distribution width indexes RDW-CV and RDW-SD (P<0.05).Conclusions. An adequate therapeutic effect was achieved with standard doses of anti-TB medications in patients with intermediate acetylation type. Rapid and slow acetylators required anti-TB medication dose correction. Genotyping for NAT2 gene in patients with pulmonary TB enables clinicians to choose the optimal dose of anti-TB medications, specifically, isoniazid dose.


Author(s):  
Hamidi Abdul Aziz ◽  
Nur Syahirah Rahmat ◽  
Motasem Y. D. Alazaiza

Chemical-based coagulants and flocculants are commonly used in the coagulation–flocculation process. However, the drawbacks of using these chemical materials have triggered researchers to find natural materials to substitute or reduce the number of chemical-based coagulants and flocculants. This study examines the potential application of Nephelium lappaceum seeds as a natural coagulant–coagulant aid with Tin (IV) chloride (SnCl4) in eliminating suspended solids (SS), colour, and chemical oxygen demand (COD) from landfill leachate. Results showed that the efficiency of Nephelium lappaceum was low when used as the main coagulant in the standard jar test. When SnCl4 was applied as a single coagulant, as much as 98.4% of SS, 96.8% of colour and 82.0% of COD was eliminated at an optimal dose of 10.5 g/L and pH 7. The higher removal efficiency of colour (88.8%) was obtained when 8.40 g/L of SnCl4 was applied with a support of 3 g/L of Nephelium lappaceum. When SnCl4 was utilised as a coagulant, and Nephelium lappaceum seed was used as a flocculant, the removal of pollutants generally improved. Overall, this research showed that Nephelium lappaceum seed is a viable natural alternative for treating landfill leachate as a coagulant aid.


ScienceRise ◽  
2021 ◽  
pp. 18-24
Author(s):  
Olena Bilyk ◽  
Yulia Bondarenko ◽  
Oksana Kochubei-Lytvynenko ◽  
Liudmyla Burchenko

The object of research is the technology of bakery products enriched with a mixture of germinated grains of wheat, corn, barley and oats. Investigated problem: The problem of using a mixture of germinated grains is the formation of a closure sticky crumb in baked goods with a mixture. The reason for this is the high activity in the mixture of amylolytic and proteolytic enzymes. The solution to the problem consists in the developed multicomponent mixture (MM) to improve the consumer properties of bakery products, the formulation of which includes 15 % of the flour mass of the germinated grain mixture. Main scientific results: On the basis of experimental studies, the formulation of the "Solodok+" multicomponent mixture has been developed. The mixture contains: chicory inulin, dry milk whey enriched with Mg and Mn, apple pectin, phosphatide concentrate, enzyme preparation Deltamalt FN-A 50 and ascorbic acid. The optimal dose of the "Solodok+" MM for bakery products is 2.5 % by weight of flour. The area of practical use of the research results: "Solodok+" MM is recommended to be used in the production of bakery products enriched with sprouted grains at enterprises of the bakery industry of various capacities. An innovative technological product: "Solodok+" MM helps not only to reduce the stickiness of the crumb, improve its porosity, increase the volume of products, but also lengthen the freshness of unpackaged products. Scope of application of the innovative technological product: Bakery products with a mixture of sprouted grains and "Solodok+" MM have increased nutritional value, high consumer properties and are intended for a wide range of consumers.


2021 ◽  
Vol 215 (12) ◽  
pp. 50-58
Author(s):  
Al'bina Luneva

Abstract. The purpose of the research. Screening of collection strains of microorganisms with enzymatic properties to accelerate the processes of microbial biodegradation of bird droppings. Research methods. The proteolytic activity of the grown cultures was studied according to GOST 20264.2-88, the total microbial number in the chicken droppings (CFU/ml) was analyzed, and the ammonium nitrogen was determined. Research results. As a result of the experiments, it was found that the highest proteolytic activity was demonstrated by the strain Pseudomonas putida 90 biovar A (171), which amounted to 74.6 units/g. When analyzing the effect of the studied collection strains on the decomposition processes of droppings, it was revealed that the largest number of microbial cells in bird droppings was achieved using Pseudomonas putida 90 biovar A (171), which was 104 CFU/ml at the beginning of the researches, and was the maximum and amounted to 1011 CFU/ml by the 15th day. The content of ammonium nitrogen in droppings treated with this culture decreased from 340 mg/l from the beginning of the experiment to 174 (15th day) and 169 mg/l (20th day) and it was the best indicator. When selecting the dose and concentration of the strain-producer Pseudomonas putida 90 biovar A (171) under introduction to bird droppings, it was found that to accelerate the process of biodegradation of bird droppings, the optimal dose for applying the studied culture is 4.0 % of organic waste mass with preliminary dilution by 2 times with water. At the same time, the optimal time of droppings keeping and the studied culture is 15 days. Scientific novelty. It was established for the first time that the treatment of chicken manure with the collection strain Pseudomonas putida 90 biovar A (171) accelerates the process of its microbial transformation.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jian Han ◽  
Lu Liu ◽  
Li Meng ◽  
Huan Guo ◽  
Jin Zhang ◽  
...  

Study of the association between single nucleotide polymorphisms (SNPs) of methotrexate (MTX) pathway genes and MTX-related toxicity in the treatment of hematological malignancies is popular. Here, we studied the association between SNPs of MTHFR and ABCB1 and MTX-related toxicity in 157 adult Chinese patients diagnosed with hematological malignancies. Patients were genotyped for MTHFR rs1801131, MTHFR rs1801133, and ABCB1 rs1045642 by fluorescence in situ hybridization. Patients with MTHFR rs1801133T allele had a significantly higher risk of hematopoietic toxicity compared with those with CC genotype (p=0.003). With respect to MTHFR rs1801131, patients with CC and AC genotypes had significantly lower frequency of hematopoietic toxicity than patients with AA genotype (p=0.044). In conclusion, we identified an important influence of the SNPs of ABCB1 and MTHFR on MTX-related hematopoietic toxicity in adults with hematological malignancies. To optimize high-dose (HD)-MTX therapy and reduce related hematopoietic toxicity, it is necessary to detect the SNPs of MTHFR and ABCB1 before initiating HD-MTX and deciding the optimal dose of MTX and duration of leucovorin rescue, according to genetic tests and disease type in adults with hematological malignancies.


2021 ◽  
Vol 23 (104) ◽  
pp. 55-59
Author(s):  
N. Cherniy ◽  
I. Skvortsova ◽  
B. Gutyj ◽  
R. Mylostyvyi ◽  
V. Voronyak

The results of the studies on the determination of the optimal dose of the probiotic additive “Evitalia” (PAE) for the quails of the Texas breed have been presented in the article. The experiments were conducted on the quails aged 1–35 days. The object of the research was the probiotic additive “Evitalia” that consisted of eight components (the strains of lactic acidmicroorganisms, macro- and microelements). The subject of the investigation was the influence of PAE on the growth, preservation, the morphological composition and biochemical indices of blood. The studies were carried out in the following conditions of microclimate and sanitary regime: the air temperature in the pens-cages was 16–18 ºC in the autumn and winter period that was 5–7 ºC lower than it was provided by the standard; in spring the temperature was 23–15 ºС that was lower than it was provided by the standard (29–35 ºС). The concentration of carbon dioxide ranged within 0.20–0.25 % (2.0–2.5 l/m3), ammonia – 12–13.4 mg/m3, the general contamination of the air by microflora was 50–60 thousand KOE/m3. The experiments were conducted on the four groups of quails, 60 quails in each group. The quails of the control group were fed by water without PAE, the probiotic at the dose of 7 mg/500 ml of water was given to the quails of the experimental group 1 (E-1), 9 mg of probiotic/500 ml water received the birds of the experimental group 2 (E-2) and the quails of the experimental group 3 (E-3) were given the probiotic at the dose of 11 mg/500 ml water. The positive influence of the probiotic additive “Evitalia” on the growth and the body live weight gain of the quails was observedin the experimental groups as compared to the quails of the control group. The trustworthy increase in the growth and live weight gain of the quails was detected on the 7-, 14-, 21-, 35-day of their life (Р < 0.05), especially in the quails that received PAE at the dose of 9 mg (E-2). The quails of the experimental group 2 exceeded the others by the average daily live weight gains. The growth intensity of the quails in the experimental group 2 was 6.43 % higher than that of the control one, higher by 3.47 % and 5.57 % than in the experimental groups 1 and 3, respectively. The preservation of the quails in the control group was lower by 4.8 – 5.1 % as compared to the quails in the experimental groups. By the data on the growth of the body live weight, the composition and biochemical indices of blood of the quails it can be concluded that the optimal dose of the probioticadditive “Evitalia” is 9 mg/500 ml water that activates hematopoesis and stimulates the growth and development of quails.


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