scholarly journals Reaction of Chalcones with Cellular Thiols. The Effect of the 4-Substitution of Chalcones and Protonation State of the Thiols on the Addition Process. Diastereoselective Thiol Addition

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4332
Author(s):  
Fatemeh Kenari ◽  
Szilárd Molnár ◽  
Pál Perjési
Keyword(s):  
Biological Effects ◽  
Equilibrium Composition ◽  
Deprotonated Form ◽  
Degree Of Ionization ◽  
Thiol Reactivity ◽  
Michael Type Addition ◽  
Ph Conditions ◽  
The Difference ◽  
Initial Reactivity

Several biological effects of chalcones have been reported to be associated with their thiol reactivity. In vivo, the reactions can result in the formation of small-molecule or protein thiol adducts. Both types of reactions can play a role in the biological effects of this class of compounds. Progress of the reaction of 4-methyl- and 4-methoxychalcone with glutathione and N-acetylcysteine was studied by the HPLC-UV-VIS method. The reactions were conducted under three different pH conditions. HPLC-MS measurements confirmed the structure of the formed adducts. The chalcones reacted with both thiols under all incubation conditions. The initial rate and composition of the equilibrium mixtures depended on the ratio of the deprotonated form of the thiols. In the reaction of 4-methoxychalcone with N-acetylcysteine under strongly basic conditions, transformation of the kinetic adduct into the thermodynamically more stable one was observed. Addition of S-protonated N-acetylcysteine onto the polar double bonds of the chalcones showed different degrees of diastereoselectivity. Both chalcones showed a Michael-type addition reaction with the ionized and non-ionized forms of the investigated thiols. The initial reactivity of the chalcones and the equilibrium composition of the incubates showed a positive correlation with the degree of ionization of the thiols. Conversions showed systematic differences under each set of conditions. The observed differences can hint at the difference in reported biological actions of 4-methyl- and 4-methoxy-substituted chalcones.

Enhancement of ADP-induced Platelet Aggregation by Adrenaline in Vivo and Its Prevention

1973 ◽  
Vol 29 (02) ◽  
pp. 490-498 ◽  
Author(s):  
Hiroh Yamazaki ◽  
Itsuro Kobayashi ◽  
Tadahiro Sano ◽  
Takio Shimamoto
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
The Other ◽  
Endothelial Surface ◽  
Important Interaction ◽  
Blood Coagulability ◽  
The Difference

SummaryThe authors previously reported a transient decrease in adhesive platelet count and an enhancement of blood coagulability after administration of a small amount of adrenaline (0.1-1 µg per Kg, i. v.) in man and rabbit. In such circumstances, the sensitivity of platelets to aggregation induced by ADP was studied by an optical density method. Five minutes after i. v. injection of 1 µg per Kg of adrenaline in 10 rabbits, intensity of platelet aggregation increased to 115.1 ± 4.9% (mean ± S. E.) by 10∼5 molar, 121.8 ± 7.8% by 3 × 10-6 molar and 129.4 ± 12.8% of the value before the injection by 10”6 molar ADP. The difference was statistically significant (P<0.01-0.05). The above change was not observed in each group of rabbits injected with saline, 1 µg per Kg of 1-noradrenaline or 0.1 and 10 µg per Kg of adrenaline. Also, it was prevented by oral administration of 10 mg per Kg of phenoxybenzamine or propranolol or aspirin or pyridinolcarbamate 3 hours before the challenge. On the other hand, the enhancement of ADP-induced platelet aggregation was not observed in vitro, when 10-5 or 3 × 10-6 molar and 129.4 ± 12.8% of the value before 10∼6 molar ADP was added to citrated platelet rich plasma (CPRP) of rabbit after incubation at 37°C for 30 second with 0.01, 0.1, 1, 10 or 100 µg per ml of adrenaline or noradrenaline. These results suggest an important interaction between endothelial surface and platelets in connection with the enhancement of ADP-induced platelet aggregation by adrenaline in vivo.

Reliability of a Single β-Thromboglobulin Measurement in a Diabetic Population : Importance of PGE1 in Anticoagulant Mixture

1987 ◽  
Vol 57 (02) ◽  
pp. 201-204 ◽  
Author(s):  
P Y Scarabin ◽  
L Strain ◽  
C A Ludlam ◽  
J Jones ◽  
E M Kohner
Keyword(s):  
In Vitro Release ◽  
Mean Value ◽  
Reliable Estimate ◽  
Diabetic Patients ◽  
Single Measurement ◽  
Diabetic Population ◽  
The Difference ◽  
Vitro Release

SummaryDuring the collection of samples for plasma β-thromboglobulin (β-TG) determination, it is well established that artificially high values can be observed due to in-vitro release. To estimate the reliability of a single β-TG measurement, blood samples were collected simultaneously from both arms on two separate occasions in 56 diabetic patients selected for a clinical trial. From each arm, blood was taken into two tubes containing an anticoagulant mixture with (tube A) and without (tube B) PGE!. The overall mean value of B-TG in tube B was 1.14 times higher than in tube A (p <0.01). The markedly large between-arms variation accounted for the most part of within-subject variation in both tubes and was significantly greater in tube B than in tube A. Based on the difference between B-TG values from both arms, the number of subjects with artifically high B-TG values was significantly higher in tube B than in tube A on each occasion (overall rate: 28% and 14% respectively). Estimate of between-occasions variation showed that B-TG levels were relatively stable for each subject between two occasions in each tube. It is concluded that the use of PGEi decreases falsely high B-TG levels, but a single measurement of B-TG does not provide a reliable estimate of the true B-TG value in vivo.

The role of aromatic microbial metabolites

2018 ◽  
pp. 97-108
Author(s):  
Н.В. Белобородова ◽  
В.В. Мороз ◽  
А.Ю. Бедова
Keyword(s):  
Process Integration ◽  
Biological Effects ◽  
Clinical Findings ◽  
Multiple Organ ◽  
Critical Conditions ◽  
Clear Understanding ◽  
Microbial Metabolites ◽  
Blood Concentrations

Интеграция метаболизма макроорганизма и его микробиоты, обеспечивающая в норме симбиоз и саногенез, нарушается при заболеваниях, травме, критическом состоянии, и вектор взаимодействия может изменяться в пользу прокариотов по принципу «метаболиты бактерий - против хозяина». Анализ литературы показал, что, с одной стороны, имеется живой интерес к ароматическим микробным метаболитам, с другой - отсутствует четкое представление об их роли в организме человека. Публикации, касающиеся ряда ароматических микробных метаболитов (фенилкарбоновых кислот, ФКК), как правило, не связаны между собой по тематике и направлены на решение тех или иных прикладных задач в разных областях биологии и медицины. Цель обзора - анализ информации о происхождении, биологических эффектах ФКК в экспериментах in vitro и in vivo , и клинических наблюдениях. Обобщая результаты приведенных в обзоре исследований на клеточном, субклеточном и молекулярном уровнях, логично предположить участие ароматических микробных метаболитов в патогенезе полиорганной недостаточности при сепсисе. Наиболее перспективным для раскрытия роли ароматических микробных метаболитов представляется изучение механизмов вторичной почечной недостаточности и септической энцефалопатии. Важным направлением для будущих исследований является изучение влияния продуктов микробной биодеградации ароматических соединений на развитие диссеминированного внутрисосудистого свертывания крови, артериальной гипотензии и септического шока. Результаты дальнейших исследований будут иметь не только фундаментальное значение, но и обогатят практическую медицину новыми диагностическими и лечебными технологиями. Significant increases in blood concentrations of some aromatic metabolites (phenylcarboxylic acids, PhCAs) in patients with sepsis have been previously shown. Enhanced bacterial biodegradation of aromatic compounds has been demonstrated to considerably contribute to this process. Integration of macroorganism metabolism and its microbiota, which provides normal symbiosis and sanogenesis, is disturbed in diseases, trauma, and critical conditions. Direction of this interaction may change in favor of prokaryotes according to the principle, “bacterial metabolites are against the host”. Analysis of literature showed a particular interest of many investigators to aromatic microbial metabolites. However, there is no clear understanding of their role in the human body. Publications on PhCAs are generally not thematically interrelated and usually focus on solving applied tasks in different fields of biology and medicine. The aim of this work was to consolidate existing information about origin and biological effects of PhCAs in in vitro / in vivo experiments and some clinical findings. The presented summary of reported data from studies performed at cellular, sub-cellular, and molecular levels suggests participation of aromatic microbial metabolites in the pathogenesis of multiple organ failure in sepsis. Studying mechanisms of secondary renal failure and septic encephalopathy is most promising for discovering the function of aromatic microbial metabolites. Effects of microbial biodegradation products of aromatic substances on development of disseminated intravascular coagulation, hypotension, and septic shock are an important challenge for future studies. Results of further investigations will be not only fundamental, but will also enrich medical practice with new diagnostic and therapeutic technologies.

Antioxidant Activity, Phenolic Content and Hematoprotective Effects of Cleome arabica Polyphenolic Leaf Extract

2019 ◽  
Author(s):  
C. Tigrine ◽  
A. Kameli
Keyword(s):  
Antioxidant Activity ◽  
Biological Effects ◽  
Reducing Power ◽  
Hematological Toxicity ◽  
Protective Effects ◽  
Ferrous Ions ◽  
Polyphenolic Extract ◽  
Cleome Arabica

In this study a polyphenolic extract from Cleome arabica leaves (CALE) was investigated for its antioxidant activity in vitro using DPPH•, metal chelating and reducing power methods and for its protective effects against AraC-induced hematological toxicity in vivo using Balb C mice. Results indicated that CALE exhibited a strong and dose-dependent scavenging activity against the DPPH• free radical (IC50 = 4.88 μg/ml) and a high reducing power activity (EC50 = 4.85 μg/ml). Furthermore, it showed a good chelating effects against ferrous ions (IC50 = 377.75 μg/ml). The analysis of blood showed that subcutaneous injection of AraC (50 mg/kg) to mice during three consecutive days caused a significant myelosupression (P < 0.05). The combination of CALE and AraC protected blood cells from a veritable toxicity. Where, the number of the red cells, the amount of hemoglobin and the percentage of the hematocrite were significantly high. On the other hand, AraC cause an elevation of body temperature (39 °C) in mice. However, the temperature of the group treated with CALE and AraC remained normal and did not exceed 37.5 °C. The observed biological effects of CALE, in vitro as well as in vivo, could be due to the high polyphenol and flavonoid contents. In addition, the antioxidant activity of CALE suggested to be responsible for its hematoprotective effect.

Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity

2019 ◽  
Vol 26 (7) ◽  
pp. 494-501 ◽  
Author(s):  
Sameer Suresh Bhagyawant ◽  
Dakshita Tanaji Narvekar ◽  
Neha Gupta ◽  
Amita Bhadkaria ◽  
Ajay Kumar Gautam ◽  
...  
Keyword(s):  
Biological Effects ◽  
Exchange Chromatography ◽  
Health Concern ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ic50 Values ◽  
Chickpea Lectin

Background: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. Methods: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. Results: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. Conclusion: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.

Pleiotropic Effect of Mahanine and Girinimbine Analogs: Anticancer Mechanism and its Therapeutic Versatility

2019 ◽  
Vol 18 (14) ◽  
pp. 1983-1990 ◽  
Author(s):  
V. Lenin Maruthanila ◽  
Ramakrishnan Elancheran ◽  
Ajaikumar B. Kunnumakkar ◽  
Senthamaraikannan Kabilan ◽  
Jibon Kotoky
Keyword(s):  
Biological Effects ◽  
Pleiotropic Effect ◽  
In Vivo Evaluation ◽  
Chemopreventive Agents ◽  
Cycle Arrest ◽  
Wide Range ◽  
Anticancer Mechanism ◽  
Metastasis Development

Emerging evidence present credible support in favour of the potential role of mahanine and girinimbine. Non-toxic herbal carbazole alkaloids occur in the edible part of Murraya koenigii, Micromelum minutum, M. zeylanicum, and M. euchrestiolia. Mahanine and girinimbine are the major potent compounds from these species. In fact, they interfered with tumour expansion and metastasis development through down-regulation of apoptotic and antiapoptotic protein, also involved in the stimulation of cell cycle arrest. Consequently, these compounds were well proven for the in-vitro and in vivo evaluation that could be developed as novel agents either alone or as an adjuvant to conventional therapeutics. Therefore, mahanine and girinimbine analogs have the potential to be the promising chemopreventive agents for the tumour recurrence and the treatment of human malignancies. In this review, an updated wide-range of pleiotropic anticancer and biological effects induction by mahanine and girinimbine against cancer cells were deeply summarized.

scholarly journals Force Generation on the Hallux Is More Affected by the Ankle Joint Angle than the Lesser Toes: An In Vivo Human Study

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 48
Author(s):  
Junya Saeki ◽  
Soichiro Iwanuma ◽  
Suguru Torii
Keyword(s):  
Repeated Measures ◽  
Joint Angle ◽  
Plantar Flexion ◽  
Human Study ◽  
Force Generation ◽  
Functional Difference ◽  
Multiple Comparison Test ◽  
The Difference ◽  
Metatarsophalangeal Joints

The structure of the first toe is independent of that of the other toes, while the functional difference remains unclear. The purpose of this study was to investigate the difference in the force generation characteristics between the plantar-flexion of the first and second–fifth metatarsophalangeal joints (MTPJs) by comparing the maximal voluntary plantar-flexion torques (MVC torque) at different MTPJs and ankle positions. The MVC torques of the first and second–fifth MTPJs were measured at 0°, 15°, 30°, and 45° dorsiflexed positions of the MTPJs, and at 20° plantar-flexed, neutral, and 20° dorsiflexed positions of the ankle. Two-way repeated measures analyses of variance with Holm’s multiple comparison test (MTPJ position × ankle position) were performed. When the MTPJ was dorsiflexed at 0°, 15°, and 30°, the MVC torque of the first MTPJ when the ankle was dorsiflexed at 20° was higher than that when the ankle was plantar-flexed at 20°. However, the ankle position had no significant effect on the MVC torque of the second–fifth MTPJ. Thus, the MVC torque of the first MTPJ was more affected by the ankle position than the second–fifth MTPJs.

scholarly journals Biological Effects of β-Glucans on Osteoclastogenesis

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1982
Author(s):  
Wataru Ariyoshi ◽  
Shiika Hara ◽  
Ayaka Koga ◽  
Yoshie Nagai-Yoshioka ◽  
Ryota Yamasaki
Keyword(s):  
Bone Resorption ◽  
Bone Marrow Cells ◽  
Biological Effects ◽  
Osteoclast Differentiation ◽  
Treatment Strategies ◽  
Alcaligenes Faecalis ◽  
Osteoclast Formation ◽  
Osteoclast Precursors

Although the anti-tumor and anti-infective properties of β-glucans have been well-discussed, their role in bone metabolism has not been reviewed so far. This review discusses the biological effects of β-glucans on bone metabolisms, especially on bone-resorbing osteoclasts, which are differentiated from hematopoietic precursors. Multiple immunoreceptors that can recognize β-glucans were reported to be expressed in osteoclast precursors. Coordinated co-stimulatory signals mediated by these immunoreceptors are important for the regulation of osteoclastogenesis and bone remodeling. Curdlan from the bacterium Alcaligenes faecalis negatively regulates osteoclast differentiation in vitro by affecting both the osteoclast precursors and osteoclast-supporting cells. We also showed that laminarin, lichenan, and glucan from baker’s yeast, as well as β-1,3-glucan from Euglema gracilisas, inhibit the osteoclast formation in bone marrow cells. Consistent with these findings, systemic and local administration of β-glucan derived from Aureobasidium pullulans and Saccharomyces cerevisiae suppressed bone resorption in vivo. However, zymosan derived from S. cerevisiae stimulated the bone resorption activity and is widely used to induce arthritis in animal models. Additional research concerning the relationship between the molecular structure of β-glucan and its effect on osteoclastic bone resorption will be beneficial for the development of novel treatment strategies for bone-related diseases.

scholarly journals A therapeutic vascular conduit to support in vivo cell-secreted therapy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Edward X. Han ◽  
Hong Qian ◽  
Bo Jiang ◽  
Maria Figetakis ◽  
Natalia Kosyakova ◽  
...  
Keyword(s):  
Vascular Graft ◽  
Large Scale ◽  
Biological Effects ◽  
Therapeutic Protein ◽  
Close Proximity ◽  
Delivery Platform ◽  
Stage Renal Disease ◽  
End Stage

AbstractA significant barrier to implementation of cell-based therapies is providing adequate vascularization to provide oxygen and nutrients. Here we describe an approach for cell transplantation termed the Therapeutic Vascular Conduit (TVC), which uses an acellular vessel as a scaffold for a hydrogel sheath containing cells designed to secrete a therapeutic protein. The TVC can be directly anastomosed as a vascular graft. Modeling supports the concept that the TVC allows oxygenated blood to flow in close proximity to the transplanted cells to prevent hypoxia. As a proof-of-principle study, we used erythropoietin (EPO) as a model therapeutic protein. If implanted as an arteriovenous vascular graft, such a construct could serve a dual role as an EPO delivery platform and hemodialysis access for patients with end-stage renal disease. When implanted into nude rats, TVCs containing EPO-secreting fibroblasts were able to increase serum EPO and hemoglobin levels for up to 4 weeks. However, constitutive EPO expression resulted in macrophage infiltration and luminal obstruction of the TVC, thus limiting longer-term efficacy. Follow-up in vitro studies support the hypothesis that EPO also functions to recruit macrophages. The TVC is a promising approach to cell-based therapeutic delivery that has the potential to overcome the oxygenation barrier to large-scale cellular implantation and could thus be used for a myriad of clinical disorders. However, a complete understanding of the biological effects of the selected therapeutic is absolutely essential.

scholarly journals Drug Delivery by Ultrasound-Responsive Nanocarriers for Cancer Treatment

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1135
Author(s):  
Kristin Entzian ◽  
Achim Aigner
Keyword(s):  
Drug Delivery ◽  
Biological Effects ◽  
Invasive Technique ◽  
Stimuli Responsive ◽  
Comprehensive Overview ◽  
Drug Concentrations ◽  
Therapeutic Outcomes ◽  
Cost Efficient ◽  
Safety Considerations

Conventional cancer chemotherapies often exhibit insufficient therapeutic outcomes and dose-limiting toxicity. Therefore, there is a need for novel therapeutics and formulations with higher efficacy, improved safety, and more favorable toxicological profiles. This has promoted the development of nanomedicines, including systems for drug delivery, but also for imaging and diagnostics. Nanoparticles loaded with drugs can be designed to overcome several biological barriers to improving efficiency and reducing toxicity. In addition, stimuli-responsive nanocarriers are able to release their payload on demand at the tumor tissue site, preventing premature drug loss. This review focuses on ultrasound-triggered drug delivery by nanocarriers as a versatile, cost-efficient, non-invasive technique for improving tissue specificity and tissue penetration, and for achieving high drug concentrations at their intended site of action. It highlights aspects relevant for ultrasound-mediated drug delivery, including ultrasound parameters and resulting biological effects. Then, concepts in ultrasound-mediated drug delivery are introduced and a comprehensive overview of several types of nanoparticles used for this purpose is given. This includes an in-depth compilation of the literature on the various in vivo ultrasound-responsive drug delivery systems. Finally, toxicological and safety considerations regarding ultrasound-mediated drug delivery with nanocarriers are discussed.

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