Polycystic ovary syndrome (PCOS) is an endocrine-gynecology disorder affecting many women of childbearing age. Although a part of the involved mechanism in PCOS occurrence is discovered, the exact ...etiology and pathophysiology are not comprehensively understood yet. We searched PubMed for PCOS pathogenesis and management in this article and ClinicalTrials.gov for information on repurposed medications. All responsible factors behind PCOS were thoroughly evaluated. Furthermore, the complete information on PCOS commonly prescribed and repurposed medications is summarized through tables. Epigenetics, environmental toxicants, stress, diet as external factors, insulin resistance, hyperandrogenism, inflammation, oxidative stress, and obesity as internal factors were investigated. Lifestyle modifications and complementary and alternative medicines are preferred first-line therapy in many cases. Medications, including 3-hydroxy-3-methyl-3-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, thiazolidinediones, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, glucose-like peptide-1 receptor agonists, mucolytic agents, and some supplements have supporting data for being repurposed in PCOS. Since there are few completed clinical trials with a low population and mostly without results on PCOS repurposed medications, it would be helpful to do further research and run well-designed clinical trials on this subject. Moreover, understanding more about PCOS would be beneficial to find new medications implying the effect via the novel discovered routes.
Oxidative stress plays an essential role in the pathogenesis of chronic diseases such as cardiovascular diseases, diabetes, neurodegenerative diseases, and cancer. Long term exposure to increased ...levels of pro-oxidant factors can cause structural defects at a mitochondrial DNA level, as well as functional alteration of several enzymes and cellular structures leading to aberrations in gene expression. The modern lifestyle associated with processed food, exposure to a wide range of chemicals and lack of exercise plays an important role in oxidative stress induction. However, the use of medicinal plants with antioxidant properties has been exploited for their ability to treat or prevent several human pathologies in which oxidative stress seems to be one of the causes. In this review we discuss the diseases in which oxidative stress is one of the triggers and the plant-derived antioxidant compounds with their mechanisms of antioxidant defenses that can help in the prevention of these diseases. Finally, both the beneficial and detrimental effects of antioxidant molecules that are used to reduce oxidative stress in several human conditions are discussed.
The use of plant secondary metabolites has gained considerable attention among clinicians in the prevention and treatment of cancer. A secondary metabolite isolated mainly from the roots and rhizomes ...of Podophyllum species (Berberidaceae) is aryltetralin lignan - podophyllotoxin (PTOX). The purpose of this review is to discuss the therapeutic properties of PTOX as an important anticancer compound of natural origin. The relevant information regarding the antitumor mechanisms of podophyllotoxin and its derivatives were collected and analyzed from scientific databases. The results of the analysis showed PTOX exhibits potent cytotoxic activity; however, it cannot be used in its pure form due to its toxicity and generation of many side effects. Therefore, it practically remains clinically unusable. Currently, high effort is focused on attempts to synthesize analogs of PTOX that have better properties for therapeutic use e.g. etoposide (VP-16), teniposide, etopophos. PTOX derivatives are used as anticancer drugs which are showing additional immunosuppressive, antiviral, antioxidant, hypolipemic, and anti-inflammatory effects. In this review, attention is paid to the high potential of the usefulness of in vitro cultures of P. peltatum which can be a valuable source of lignans, including PTOX. In conclusion, the preclinical pharmacological studies in vitro and in vivo confirm the anticancer and chemotherapeutic potential of PTOX and its derivatives. In the future, clinical studies on human subjects are needed to certify the antitumor effects and the anticancer mechanisms to be certified and analyzed in more detail and to validate the experimental pharmacological preclinical studies.
Anthocyanins are natural phenolic pigments with biological activity. They are well-known to have potent antioxidant and antiinflammatory activity, which explains the various biological effects ...reported for these substances suggesting their antidiabetic and anticancer activities, and their role in cardiovascular and neuroprotective prevention. This review aims to comprehensively analyze different studies performed on this class of compounds, their bioavailability and their therapeutic potential. An in-depth look in preclinical,
and
, and clinical studies indicates the preventive effects of anthocyanins on cardioprotection, neuroprotection, antiobesity as well as their antidiabetes and anticancer effects.
The COVID-19 pandemic represents an unprecedented challenge for the researchers to offer safe, tolerable, and effective treatment strategies for its causative agent known as SARS-CoV-2. With the ...rapid evolution of the pandemic, even the off-label use of existing drugs has been restricted by limited availability. Several old antivirals, antimalarial, and biological drugs are being reconsidered as possible therapies. The effectiveness of the controversial treatment options for COVID-19 such as nonsteroidal antiinflammatory drugs, angiotensin 2 conversion enzyme inhibitors and selective angiotensin receptor blockers was also discussed. A systemic search in the PubMed, Science Direct, LitCovid, Chinese Clinical Trial Registry, and ClinicalTrials.gov data bases was conducted using the keywords “coronavirus drug therapy,” passive immunotherapy for COVID-19’, “convalescent plasma therapy,” (CPT) “drugs for COVID-19 treatment,” “SARS-CoV-2,” “COVID-19,” “2019-nCoV,” “coronavirus immunology,” “microbiology,” “virology,” and individual drug names. Systematic reviews, case presentations and very recent clinical guidelines were included. This narrative review summarizes the available information on possible therapies for COVID-19, providing recent data to health professionals.
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•mRNA and viral vector vaccines are currently used in the EU for COVID-19 prophylaxis.•EMA has assessed the safety of the three vaccines currently used in the EU.•Local and systemic ...reactions are reported during vaccinations campaigns.•Vaccine-induced immune thrombotic thrombocytopenia has been linked to Vaxzevria.•Follow-up and surveillance studies for vaccines’ safety monitoring will be needed.
The COVID-19 pandemic has had an unprecedented and devastating impact on public health, society and economics around the world. As a result, the development of vaccines to protect individuals from symptomatic COVID-19 infections has represented the only feasible health tool to combat the spread of the disease. However, at the same time the development and regulatory assessment of different vaccines has challenged pharmaceutical industries and regulatory agencies as this process has occurred in the shorter time ever though. So far, two mRNA and two adenovirus-vectored vaccines have received a conditional marketing authorisation in the EU and other countries. This review summarized and discusses the assessment reports of the European Medicine Agency (EMA) concerning the safety of the 3 vaccines currently used in the EU (Pfizer, Moderna and Astra-Zeneca). A particular focus has been paid to safety information from pre-clinical (animal) and clinical (phase 3 trials) studies. Overall, the most frequent adverse effects reported after the administration of these vaccines consisted of local reactions at the injection site (sore arm and erythema) followed by non-specific systemic effects (myalgia, chills, fatigue, headache, and fever), which occurred soon after vaccination and resolved shortly. Rare cases of vaccine-induced immune thrombotic thrombocytopenia have been reported for Vaxzevria. Data on long-term studies, interaction with other vaccines, use in pregnancy/breast-feeding, use in immunocompromised subjects, and in subjects with comorbidities, autoimmune or inflammatory disorders are still missing for these vaccines. Therefore, careful follow-up and surveillance studies for continued vaccine safety monitoring will be needed to ascertain the potential risks of such adverse events or diseases. In conclusion, the benefits and risks of current COVID-19 vaccines must be weighed against the real possibility of contract the disease and develop complications and long-term sequels; all this on the basis of the available scientific evidence and in the absence of unmotivated biases.
Chalcones are among the leading bioactive flavonoids with a therapeutic potential implicated to an array of bioactivities investigated by a series of preclinical and clinical studies. In this ...article, different scientific databases were searched to retrieve studies depicting the biological activities of chalcones and their derivatives. This review comprehensively describes preclinical studies on chalcones and their derivatives describing their immense significance as antidiabetic, anticancer, anti-inflammatory, antimicrobial, antioxidant, antiparasitic, psychoactive, and neuroprotective agents. Besides, clinical trials revealed their use in the treatment of chronic venous insufficiency, skin conditions, and cancer. Bioavailability studies on chalcones and derivatives indicate possible hindrance and improvement in relation to its nutraceutical and pharmaceutical applications. Multifaceted and complex underlying mechanisms of chalcone actions demonstrated their ability to modulate a number of cancer cell lines, to inhibit a number of pathological microorganisms and parasites, and to control a number of signaling molecules and cascades related to disease modification. Clinical studies on chalcones revealed general absence of adverse effects besides reducing the clinical signs and symptoms with decent bioavailability. Further studies are needed to elucidate their structure activity, toxicity concerns, cellular basis of mode of action, and interactions with other molecules.
Abstract
The study describes the current state of knowledge on nanotechnology and its utilization in medicine. The focus in this manuscript was on the properties, usage safety, and potentially ...valuable applications of chitosan-based nanomaterials. Chitosan nanoparticles have high importance in nanomedicine, biomedical engineering, discovery and development of new drugs. The manuscript reviewed the new studies regarding the use of chitosan-based nanoparticles for creating new release systems with improved bioavailability, increased specificity and sensitivity, and reduced pharmacological toxicity of drugs. Nowadays, effective cancer treatment is a global problem, and recent advances in nanomedicine are of great importance. Special attention was put on the application of chitosan nanoparticles in developing new system for anticancer drug delivery. Pre-clinical and clinical studies support the use of chitosan-based nanoparticles in nanomedicine. This manuscript overviews the last progresses regarding the utilization, stability, and bioavailability of drug nanoencapsulation with chitosan and their safety.
The current study aims to assess the long-term effects of very low dose exposures to a complex chemical mixture on motor performance and behavioural changes in rats. For twelve months (equivalent to ...thirty years in human terms), four groups of Sprague Dawley rats (five males and five females per group) were exposed to a thirteen chemical mixture (in drinking water) in doses of 0, 0.25, 1 and 5xADI/TDI (acceptable daily intake/tolerable daily intake) (mg/kg body weight/day). After twelve month exposure, the rats' motor performances were assessed by rotarod test, and their behavioural changes were assessed by open field exploratory test and elevated plus maze test. Exposure to the chemical mixture resulted in a statistically significant increase in the locomotor activity quantified by the number of crossings over external squares and in the spatial orientation activity quantified as the number of rearings in the lower dose group (0.25xADI/TDI) compared with the control group (p < 0.05). No significant changes were observed in the two higher dose groups (1xADI/TDI, 5xADI/TDI) compared with the control group. The administration of a very low doses of a cocktail of 13 chemicals led to a dose-dependent stimulation of the nervous system, rather than its inhibition.
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•Very low doses combined exposure to 13 chemicals revealed hormetic effects on nervous system.•Locomotor activity testing showed two phase dose-dependent effects in rats.•Spatial orientation activity showed non-monotonic response in rats.•Neurobehavioral tests disclose hormesis after exposure to chemical mixture in doses below NOAEL.
Free radicals are reactive oxygen species that constantly circulate through the body and occur as a side effect of many reactions that take place in the human body. Under normal conditions, they are ...removed from the body by antioxidant processes. If these natural mechanisms are disrupted, radicals accumulate in excess and contribute to the development of many diseases.
Relevant recent information on oxidative stress, free radicals, reactive oxidative species, and natural and synthetic antioxidants was collected by researching electronic databases such as PubMed / Medline, Web of Science, and Science Direct.
According to the analysed studies, this comprehensive review provided a recent update on oxidative stress, free radicals and antioxidants and their impact on the pathophysiology of human diseases.
To counteract the condition of oxidative stress, synthetic antioxidants must be provided from external sources to supplement the antioxidant defense mechanism internally. Because of their therapeutic potential and natural origin, medicinal plants have been reported as the main source of natural antioxidants phytocompounds. Some non-enzymatic phytocompounds such as flavonoids, polyphenols, and glutathione, along with some vitamins have been reported to possess strong antioxidant activities in vivo and in vitro studies. Thus, the present review describes, in brief, the overview of oxidative stress-directed cellular damage and the unction of dietary antioxidants in the management of different diseases. The therapeutic limitations in correlating the antioxidant activity of foods to human health were also discussed.
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