Cationic Substitutions in Hydroxyapatite: Current Status of the Derived Biofunctional Effects and Their In Vitro Interrogation Methods

High-performance bioceramics are required for preventing failure and prolonging the life-time of bone grafting scaffolds and osseous implants. The proper identification and development of materials with extended functionalities addressing socio-economic needs and health problems constitute important and critical steps at the heart of clinical research. Recent findings in the realm of ion-substituted hydroxyapatite (HA) could pave the road towards significant developments in biomedicine, with an emphasis on a new generation of orthopaedic and dentistry applications, since such bioceramics are able to mimic the structural, compositional and mechanical properties of the bone mineral phase. In fact, the fascinating ability of the HA crystalline lattice to allow for the substitution of calcium ions with a plethora of cationic species has been widely explored in the recent period, with consequent modifications of its physical and chemical features, as well as its functional mechanical and in vitro and in vivo biological performance. A comprehensive inventory of the progresses achieved so far is both opportune and of paramount importance, in order to not only gather and summarize information, but to also allow fellow researchers to compare with ease and filter the best solutions for the cation substitution of HA-based materials and enable the development of multi-functional biomedical designs. The review surveys preparation and synthesis methods, pinpoints all the explored cation dopants, and discloses the full application range of substituted HA. Special attention is dedicated to the antimicrobial efficiency spectrum and cytotoxic trade-off concentration values for various cell lines, highlighting new prophylactic routes for the prevention of implant failure. Importantly, the current in vitro biological tests (widely employed to unveil the biological performance of HA-based materials), and their ability to mimic the in vivo biological interactions, are also critically assessed. Future perspectives are discussed, and a series of recommendations are underlined.

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Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

Current Drug Targets ◽

10.2174/1389450120666190429120314 ◽

2019 ◽

Vol 20 (12) ◽

pp. 1227-1243

Author(s):

Hina Qamar ◽

Sumbul Rehman ◽

D.K. Chauhan

Keyword(s):

Side Effects ◽

Medicinal Plants ◽

Anticancer Agents ◽

Drug Targets ◽

Psidium Guajava ◽

Current Status ◽

Future Perspective ◽

Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

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The Application of the Cold Atmospheric Plasma-Activated Solutions in Cancer Treatment

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666170731115233 ◽

2018 ◽

Vol 18 (6) ◽

pp. 769-775 ◽

Cited By ~ 13

Author(s):

Dayun Yan ◽

Jonathan H. Sherman ◽

Michael Keidar

Keyword(s):

Cancer Treatment ◽

Atmospheric Plasma ◽

Current Status ◽

Cold Atmospheric Plasma ◽

Anti Cancer ◽

Long Time ◽

Key Topics ◽

The Common

Background: Over the past five years, the cold atmospheric plasma-activated solutions (PAS) have shown their promissing application in cancer treatment. Similar as the common direct cold plasma treatment, PAS shows a selective anti-cancer capacity in vitro and in vivo. However, different from the direct cold atmospheric plasma (CAP) treatment, PAS can be stored for a long time and can be used without dependence on a CAP device. The research on PAS is gradually becoming a hot topic in plasma medicine. Objectives: In this review, we gave a concise but comprehensive summary on key topics about PAS including the development, current status, as well as the main conclusions about the anti-cancer mechanism achieved in past years. The approaches to make strong and stable PAS are also summarized.

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Phytochemical, Analytical and Medicinal Studies of Holoptelea integrifolia Roxb. Planch - A Review

Current Traditional Medicine ◽

10.2174/2215083805666190521103308 ◽

2019 ◽

Vol 5 (4) ◽

pp. 270-277 ◽

Cited By ~ 2

Author(s):

Vijay Kumar ◽

Simranjeet Singh ◽

Ragini Bhadouria ◽

Ravindra Singh ◽

Om Prakash

Keyword(s):

Liquid Chromatography ◽

Thin Layer ◽

Thin Layer Chromatography ◽

High Performance ◽

Biologically Active ◽

Toxicological Studies ◽

Wide Range ◽

Layer Chromatography

Holoptelea integrifolia Roxb. Planch (HI) has been used to treat various ailments including obesity, osteoarthritis, arthritis, inflammation, anemia, diabetes etc. To review the major phytochemicals and medicinal properties of HI, exhaustive bibliographic research was designed by means of various scientific search engines and databases. Only 12 phytochemicals have been reported including biologically active compounds like betulin, betulinic acid, epifriedlin, octacosanol, Friedlin, Holoptelin-A and Holoptelin-B. Analytical methods including the Thin Layer Chromatography (TLC), High-Performance Thin Layer Chromatography (HPTLC), High-Performance Liquid Chromatography (HPLC) and Liquid Chromatography With Mass Spectral (LC-MS) analysis have been used to analyze the HI. From medicinal potency point of view, these phytochemicals have a wide range of pharmacological activities such as antioxidant, antibacterial, anti-inflammatory, and anti-tumor. In the current review, it has been noticed that the mechanism of action of HI with biomolecules has not been fully explored. Pharmacology and toxicological studies are very few. This seems a huge literature gap to be fulfilled through the detailed in-vivo and in-vitro studies.

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A novel PET tracer 18F-deoxy-thiamine: synthesis, metabolic kinetics, and evaluation on cerebral thiamine metabolism status

EJNMMI Research ◽

10.1186/s13550-020-00710-5 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Changpeng Wang ◽

Siwei Zhang ◽

Yuefei Zou ◽

Hongzhao Ma ◽

Donglang Jiang ◽

...

Keyword(s):

High Performance ◽

Specific Activity ◽

High Accumulation ◽

Metabolic Kinetics ◽

Thiamine Metabolism ◽

Pet Tracer ◽

The Status ◽

The Brain

Abstract Background Some neuropsychological diseases are associated with abnormal thiamine metabolism, including Korsakoff–Wernicke syndrome and Alzheimer’s disease. However, in vivo detection of the status of brain thiamine metabolism is still unavailable and needs to be developed. Methods A novel PET tracer of 18F-deoxy-thiamine was synthesized using an automated module via a two-step route. The main quality control parameters, such as specific activity and radiochemical purity, were evaluated by high-performance liquid chromatography (HPLC). Radiochemical concentration was determined by radioactivity calibrator. Metabolic kinetics and the level of 18F-deoxy-thiamine in brains of mice and marmosets were studied by micro-positron emission tomography/computed tomography (PET/CT). In vivo stability, renal excretion rate, and biodistribution of 18F-deoxy-thiamine in the mice were assayed using HPLC and γ-counter, respectively. Also, the correlation between the retention of cerebral 18F-deoxy-thiamine in 60 min after injection as represented by the area under the curve (AUC) and blood thiamine levels was investigated. Results The 18F-deoxy-thiamine was stable both in vitro and in vivo. The uptake and clearance of 18F-deoxy-thiamine were quick in the mice. It reached the max standard uptake value (SUVmax) of 4.61 ± 0.53 in the liver within 1 min, 18.67 ± 7.04 in the kidney within half a minute. The SUV dropped to 0.72 ± 0.05 and 0.77 ± 0.35 after 60 min of injection in the liver and kidney, respectively. After injection, kidney, liver, and pancreas exhibited high accumulation level of 18F-deoxy-thiamine, while brain, muscle, fat, and gonad showed low accumulation concentration, consistent with previous reports on thiamine distribution in mice. Within 90 min after injection, the level of 18F-deoxy-thiamine in the brain of C57BL/6 mice with thiamine deficiency (TD) was 1.9 times higher than that in control mice, and was 3.1 times higher in ICR mice with TD than that in control mice. The AUC of the tracer in the brain of marmosets within 60 min was 29.33 ± 5.15 and negatively correlated with blood thiamine diphosphate levels (r = − 0.985, p = 0.015). Conclusion The 18F-deoxy-thiamine meets the requirements for ideal PET tracer for in vivo detecting the status of cerebral thiamine metabolism.

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In Vitro Antibacterial Effect of the Methanolic Extract of the Korean Soybean Fermented Product Doenjang against Staphylococcus aureus

Animals ◽

10.3390/ani11082319 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2319

Author(s):

Klara Lalouckova ◽

Lucie Mala ◽

Petr Marsik ◽

Eva Skrivanova

Keyword(s):

Staphylococcus Aureus ◽

High Performance ◽

Methanolic Extract ◽

Bioactive Substances ◽

Microdilution Method ◽

Antibacterial Compound ◽

Fermented Product ◽

Broth Microdilution Method

Ultra-high performance liquid chromatography/mass spectrometry showed soyasaponin I and the isoflavones daidzein, genistein, and glycitein to be the main components of the methanolic extract of the Korean soybean fermented product doenjang, which is known to be a rich source of naturally occurring bioactive substances, at average contents of 515.40, 236.30, 131.23, and 29.00 ng/mg, respectively. The antimicrobial activity of the methanolic extract of doenjang against nine Staphylococcusaureus strains was determined in vitro by the broth microdilution method to investigate its potential to serve as an alternative antibacterial compound. The results suggest that the extract is an effective antistaphylococcal agent at concentrations of 2048–4096 µg/mL. Moreover, the tested extract also showed the ability to inhibit the growth of both methicillin-sensitive and methicillin-resistant animal and clinical S. aureus isolates. The growth kinetics of the chosen strains of S. aureus at the minimum inhibitory concentration of the methanolic extract of doenjang support the idea that the tested extract acts as an antibacterial compound. To the best of our knowledge, this is the first report on the antistaphylococcal action of the methanolic extract of doenjang thus, additional studies including in vivo testing are necessary to confirm this hypothesis.

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Current Status of Putative Animal Sources of SARS-CoV-2 Infection in Humans: Wildlife, Domestic Animals and Pets

Microorganisms ◽

10.3390/microorganisms9040868 ◽

2021 ◽

Vol 9 (4) ◽

pp. 868

Author(s):

Max Maurin ◽

Florence Fenollar ◽

Oleg Mediannikov ◽

Bernard Davoust ◽

Christian Devaux ◽

...

Keyword(s):

Animal Species ◽

Biological Properties ◽

Experimental Models ◽

Current Data ◽

The Body ◽

Receptor Expression ◽

Current Status ◽

Susceptible Animal

SARS-CoV-2 is currently considered to have emerged from a bat coronavirus reservoir. However, the real natural cycle of this virus remains to be elucidated. Moreover, the COVID-19 pandemic has led to novel opportunities for SARS-CoV-2 transmission between humans and susceptible animal species. In silico and in vitro evaluation of the interactions between the SARS-CoV-2 spike protein and eucaryotic angiotensin-converting enzyme 2 (ACE2) receptor have tentatively predicted susceptibility to SARS-CoV-2 infection of several animal species. Although useful, these data do not always correlate with in vivo data obtained in experimental models or during natural infections. Other host biological properties may intervene such as the body temperature, level of receptor expression, co-receptor, restriction factors, and genetic background. The spread of SARS-CoV-2 also depends on the extent and duration of viral shedding in the infected host as well as population density and behaviour (group living and grooming). Overall, current data indicate that the most at-risk interactions between humans and animals for COVID-19 infection are those involving certain mustelids (such as minks and ferrets), rodents (such as hamsters), lagomorphs (especially rabbits), and felines (including cats). Therefore, special attention should be paid to the risk of SARS-CoV-2 infection associated with pets.

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High-Throughput Identification of Organic Compounds from Polygoni Multiflori Radix Praeparata (Zhiheshouwu) by UHPLC-Q-Exactive Orbitrap-MS

Molecules ◽

10.3390/molecules26133977 ◽

2021 ◽

Vol 26 (13) ◽

pp. 3977

Author(s):

Shaoyun Wang ◽

Xiaozhu Sun ◽

Shuo An ◽

Fang Sang ◽

Yunli Zhao ◽

...

Keyword(s):

High Performance ◽

Chemical Constituents ◽

Water Extract ◽

Ethanol Extract ◽

In Vivo Studies ◽

Polygonum Multiflorum ◽

Q Exactive ◽

Orbitrap Ms

Polygoni Multiflori Radix Praeparata (PMRP), as the processed product of tuberous roots of Polygonum multiflorum Thunb., is one of the most famous traditional Chinese medicines, with a long history. However, in recent years, liver adverse reactions linked to PMRP have been frequently reported. Our work attempted to investigate the chemical constituents of PMRP for clinical research and safe medication. In this study, an effective and rapid method was established to separate and characterize the constituents in PMRP by combining ultra-high performance liquid chromatography with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). Based on the accurate mass measurements for molecular and characteristic fragment ions, a total of 103 compounds, including 24 anthraquinones, 21 stilbenes, 15 phenolic acids, 14 flavones, and 29 other compounds were identified or tentatively characterized. Forty-eight compounds were tentatively characterized from PMRP for the first time, and their fragmentation behaviors were summarized. There were 101 components in PMRP ethanol extract (PMRPE) and 91 components in PMRP water extract (PMRPW). Simultaneously, the peak areas of several potential xenobiotic components were compared in the detection, which showed that PMRPE has a higher content of anthraquinones and stilbenes. The obtained results can be used in pharmacological and toxicological research and provided useful information for further in vitro and in vivo studies.

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Phytochemical Study and In Vitro Screening Focusing on the Anti-Aging Features of Various Plants of the Greek Flora

Antioxidants ◽

10.3390/antiox10081206 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1206

Author(s):

Aimilia D. Sklirou ◽

Maria T. Angelopoulou ◽

Aikaterini Argyropoulou ◽

Eliza Chaita ◽

Vasiliki Ioanna Boka ◽

...

Keyword(s):

Plant Species ◽

High Performance ◽

High Resolution Mass Spectrometry ◽

Ultra Performance Liquid Chromatography ◽

Skin Aging ◽

Rosa Damascena ◽

Phytochemical Study ◽

Age Related

Skin health is heavily affected by ultraviolet irradiation from the sun. In addition, senile skin is characterized by major changes in the collagen, elastin and in the hyaluronan content. Natural products (NPs) have been shown to delay cellular senescence or in vivo aging by regulating age-related signaling pathways. Moreover, NPs are a preferable source of photoprotective agents and have been proven to be useful against the undesirable skin hyperpigmentation. Greek flora harvests great plant diversity with approximately 6000 plant species, as it has a wealth of NPs. Here, we report an extensive screening among hundreds of plant species. More than 440 plant species and subspecies were selected and evaluated. The extracts were screened for their antioxidant and anti-melanogenic properties, while the most promising were further subjected to various in vitro and cell-based assays related to skin aging. In parallel, their chemical profile was analyzed with High-Performance Thin-Layer Chromatography (HPTLC) and/or Ultra-Performance Liquid Chromatography High-Resolution Mass Spectrometry (UPLC-HRMS). A variety of extracts were identified that can be of great value for the cosmetic industry, since they combine antioxidant, photoprotective, anti-melanogenic and anti-aging properties. In particular, the methanolic extracts of Sideritis scardica and Rosa damascena could be worthy of further attention, since they showed interesting chemical profiles and promising properties against specific targets involved in skin aging.

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Translational Research in FLASH Radiotherapy—From Radiobiological Mechanisms to In Vivo Results

Biomedicines ◽

10.3390/biomedicines9020181 ◽

2021 ◽

Vol 9 (2) ◽

pp. 181

Author(s):

Loredana G. Marcu ◽

Eva Bezak ◽

Dylan D. Peukert ◽

Puthenparampil Wilson

Keyword(s):

Dose Rate ◽

High Dose Rate ◽

Current Status ◽

Therapeutic Window ◽

High Dose ◽

Linear Accelerators ◽

Radiation Delivery ◽

Tissue Sparing

FLASH radiotherapy, or the administration of ultra-high dose rate radiotherapy, is a new radiation delivery method that aims to widen the therapeutic window in radiotherapy. Thus far, most in vitro and in vivo results show a real potential of FLASH to offer superior normal tissue sparing compared to conventionally delivered radiation. While there are several postulations behind the differential behaviour among normal and cancer cells under FLASH, the full spectra of radiobiological mechanisms are yet to be clarified. Currently the number of devices delivering FLASH dose rate is few and is mainly limited to experimental and modified linear accelerators. Nevertheless, FLASH research is increasing with new developments in all the main areas: radiobiology, technology and clinical research. This paper presents the current status of FLASH radiotherapy with the aforementioned aspects in mind, but also to highlight the existing challenges and future prospects to overcome them.

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67 Current Status and Future Prospective of the Use of Plant Bioactive Compounds in Dairy and Beef Cattle

Journal of Animal Science ◽

10.1093/jas/skab054.222 ◽

2021 ◽

Vol 99 (Supplement_1) ◽

pp. 132-132

Author(s):

Sergio Calsamiglia ◽

Maria Rodriguez-Prado ◽

Gonzalo Fernandez-Turren ◽

Lorena Castillejos

Keyword(s):

Beef Cattle ◽

Essential Oils ◽

Average Daily Gain ◽

Rumen Fermentation ◽

Production Performance ◽

In Vivo Studies ◽

Current Status ◽

The Impact

Abstract In the last 20 years there has been extensive in vitro research on the effects of plant extracts and essential oils on rumen microbial fermentation. The main objectives have been to improve energy metabolism through a reduction in methane emissions and an increase in propionate production; and to improve protein metabolism by reducing proteolysis and deamination. While the positive results from in vitro studies has stimulated the release of commercial products based on blends of essential oils, there is limited in vivo evidence on the rumen fermentation and production performance effects. A literature search was conducted to select in vivo studies where information on rumen fermentation and animal performance was reported. For dairy cattle, we identified 37 studies of which 21 were adequate to test production performance. Ten studies reported increases and 3 decreases in milk yield. For beef cattle, we identified 20 studies with rumen fermentation profile and 22 with performance data. Average daily gain improved in 7 and decreased in 1 study. Only 1 out of 16 studies reported an improvement in feed efficiency. Data indicate that out of more than 500 products tested in vitro, only around 20 have been tested in vivo in different mixtures and doses. The use of statistical approaches will allow to describe the conditions, doses and responses in dairy and beef cattle performance. The search for postruminal effects offers another alternative use. Evidence for effects on the intestinal and systemic effects on the immune system and antioxidant status (i.e., capsicum, garlic, eugenol, cinnamaldehyde curcuma, catechins, anethol or pinene), and in the modulation of metabolic regulation (capsicum, cinnamaldehyde, curcuma or garlic) may open the opportunity for future applications. However, stability of the product in the GI tract, description of the mechanisms of action and the impact of these changes on performance needs to be further demonstrated.

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