INTRODUCTION: The widespread importance of the synthesis and modification of anticancer agents has given rise to many numbers of medicinal chemistry programs. In this regard, triazine derivatives have attracted attention due to their remarkable activity against a wide range of cancer cells. This evaluation covers work reports to define the anticancer activity, the most active synthesized compound for the target, the SAR and, when described, the probable MOA besides similarly considered to deliver complete and target-pointed data for the development of types of anti-tumour medicines of triazine derivatives. Triazine scaffold for the development of anticancer analogues. Triazine can also relate to numerous beneficial targets, and their analogues have auspicious in-vitro and in-vivo anti-tumour activity. Fused molecules can improve efficacy, and drug resistance and diminish side effects, and numerous hybrid molecules are beneath diverse stages of clinical trials, so hybrid derivatives of triazine may offer valuable therapeutic involvement for the dealing of tumours. OBJECTIVE: The objective of the recent review was to summarize the recent reports on triazine as well as its analogues with respect to its anticancer therapeutic potential. CONCLUSION: The content of the review would be helpful to update the researchers working towards the synthesis and designing of new molecules for the treatment of various types of cancer disease with the recent molecules that have been produced from the triazine scaffold. Triazine scaffolds based on 1,3,5-triazine considerably boost molecular diversity levels and enable covering chemical space in key medicinal chemistry fields.
- MeSH
- antitumorózní látky * farmakologie chemie terapeutické užití MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- nádory farmakoterapie MeSH
- triaziny * farmakologie chemie terapeutické užití MeSH
- vyvíjení léků metody MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Transcranial Magnetic Stimulation (TMS) is a non-invasive technique for analyzing the central and peripheral nervous system. TMS could be a powerful therapeutic technique for neurological disorders. TMS has also shown potential in treating various neurophysiological complications, such as depression, anxiety, and obsessive-compulsive disorders, without pain and analgesics. Despite advancements in diagnosis and treatment, there has been an increase in the prevalence of brain cancer globally. For surgical planning, mapping brain tumors has proven challenging, particularly those localized in expressive regions. Preoperative brain tumor mapping may lower the possibility of postoperative morbidity in surrounding areas. A navigated TMS (nTMS) uses magnetic resonance imaging (MRI) to enable precise mapping during navigated brain stimulation. The resulting magnetic impulses can be precisely applied to the target spot in the cortical region by employing nTMS. This review focuses on nTMS for preoperative planning for brain cancer. This study reviews several studies on TMS and its subtypes in treating cancer and surgical planning. nTMS gives wider and improved dimensions of preoperative planning of the motor-eloquent areas in brain tumor patients. nTMS also predicts postoperative neurological deficits, which might be helpful in counseling patients. nTMS have the potential for finding possible abnormalities in the motor cortex areas.
- MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- mapování mozku metody MeSH
- motorické korové centrum diagnostické zobrazování MeSH
- nádory mozku * chirurgie MeSH
- neuronavigace metody MeSH
- předoperační péče * metody MeSH
- transkraniální magnetická stimulace * metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The foundations of cell reprogramming were laid by Yamanaka and co-workers, who showed that somatic cells can be reprogrammed into pluripotent cells (induced pluripotency). Since this discovery, the field of regenerative medicine has seen advancements. For example, because they can differentiate into multiple cell types, pluripotent stem cells are considered vital components in regenerative medicine aimed at the functional restoration of damaged tissue. Despite years of research, both replacement and restoration of failed organs/ tissues have remained elusive scientific feats. However, with the inception of cell engineering and nuclear reprogramming, useful solutions have been identified to counter the need for compatible and sustainable organs. By combining the science underlying genetic engineering and nuclear reprogramming with regenerative medicine, scientists have engineered cells to make gene and stem cell therapies applicable and effective. These approaches have enabled the targeting of various pathways to reprogramme cells, i.e., make them behave in beneficial ways in a patient-specific manner. Technological advancements have clearly supported the concept and realization of regenerative medicine. Genetic engineering is used for tissue engineering and nuclear reprogramming and has led to advances in regenerative medicine. Targeted therapies and replacement of traumatized , damaged, or aged organs can be realized through genetic engineering. Furthermore, the success of these therapies has been validated through thousands of clinical trials. Scientists are currently evaluating induced tissue-specific stem cells (iTSCs), which may lead to tumour-free applications of pluripotency induction. In this review, we present state-of-the-art genetic engineering that has been used in regenerative medicine. We also focus on ways that genetic engineering and nuclear reprogramming have transformed regenerative medicine and have become unique therapeutic niches.
- MeSH
- genetické inženýrství MeSH
- indukované pluripotentní kmenové buňky metabolismus cytologie MeSH
- lidé MeSH
- přeprogramování buněk * MeSH
- regenerativní lékařství * MeSH
- tkáňové inženýrství MeSH
- vývojová biologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Neurodegenerative disease (ND) incidence has recently increased due to improved life expectancy. Alzheimer's (AD) or Parkinson's disease (PD) are the most prevalent NDs. Both diseases are poly genetic, multifactorial and heterogenous. Preventive medicine, a healthy diet, exercise, and controlling comorbidities may delay the onset. After the diseases are diagnosed, therapy is needed to slow progression. Recent studies show that local, peripheral and age-related inflammation accelerates NDs' onset and progression. Patients with autoimmune disorders like inflammatory bowel disease (IBD) could be at higher risk of developing AD or PD. However, no increase in ND incidence has been reported if the patients are adequately diagnosed and treated. Autoantibodies against abnormal tau, β amyloid and α- synuclein have been encountered in AD and PD and may be protective. This discovery led to the proposal of immune-based therapies for AD and PD involving monoclonal antibodies, immunization/ vaccines, pro-inflammatory cytokine inhibition and anti-inflammatory cytokine addition. All the different approaches have been analysed here. Future perspectives on new therapeutic strategies for both disorders are concisely examined.
Organophosphorus compounds (OP) make up an important class of inhibitors, mostly employed as pesticides, even as chemical weapons. These toxic substances act through the inhibition of the acetylcholinesterase (AChE) enzyme, which results in elevated synaptic acetylcholine (ACh) levels, leading to serious adverse effects under the cholinergic syndrome. Many reactivators have been developed to combat the toxic effects of these AChE inhibitors. In this line, the oximes highlight because of their good reactivating power of cholinesterase enzymes. To date, no universal antidotes can reactivate AChE inhibited by any OP agent. This review summarizes the intoxication process by neurotoxic OP agents, along with the development of reactivators capable of reversing their effects, approaching aspects like the therapeutic and toxicological profile of these antidotes. Computational methods and conscious in vitro studies, capable of significantly predicting the toxicological profile of these drug candidates, might support the process of development of these reactivators before entering in vivo studies in animals, and then clinical trials. These approaches can assist in the design of safer and more effective molecules, reducing related cost and time for the process.
- MeSH
- acetylcholinesterasa chemie MeSH
- antidota * farmakologie terapeutické užití chemie MeSH
- cholinesterasové inhibitory toxicita MeSH
- organofosforové sloučeniny MeSH
- oximy terapeutické užití toxicita MeSH
- reaktivátory cholinesterázy * terapeutické užití toxicita MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Cancer stem cells (CSCs) are transformed forms of normal stem cells within heterogeneous mixture of cancer cells. These are mainly responsible for the recurrence of cancer after treatment because of their ability to develop resistance against chemo and radiotherapy due to various factors such as activation of signalling pathways important for self-renewal, DNA repair capacity, microenvironment and expression of ABC transporters. Targeting these mechanisms as potential factors can eliminate CSCs, which eventually decreases cancer recurrence. This review focuses on the characteristics of CSCs, their role in the development of resistance to chemotherapy and radiotherapy along with the therapeutic potential targets for successful elimination of CSC population.
- MeSH
- lidé MeSH
- nádorové kmenové buňky metabolismus MeSH
- nádorové mikroprostředí MeSH
- nádory * radioterapie farmakoterapie MeSH
- signální transdukce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Viruses have been classified as non-living because they require a cellular host to support their replicative processes. Empirical investigations have significantly advanced our understanding of the many strategies employed by viruses to usurp and divert host regulatory and metabolic processes to drive the synthesis and release of infectious particles. The recent emergence of SARS-CoV-2 has permitted us to evaluate and discuss a potentially novel classification of viruses as living entities. The ability of SARS CoV-2 to engender comprehensive regulatory control of integrative cellular processes is strongly suggestive of an inherently dynamic informational registry that is programmatically encoded by linear ssRNA sequences responding to distinct evolutionary constraints. Responses to positive evolutionary constraints have resulted in a single-stranded RNA viral genome that occupies a threedimensional space defined by conserved base-paring resulting from a complex pattern of both secondary and tertiary structures. Additionally, regulatory control of virus-mediated infectious processes relies on extensive protein-protein interactions that drive conformational matching and shape recognition events to provide a functional link between complementary viral and host nucleic acid and protein domains. We also recognize that the seamless integration of complex replicative processes is highly dependent on the precise temporal matching of complementary nucleotide sequences and their corresponding structural and non-structural viral proteins. Interestingly, the deployment of concerted transcriptional and translational activities within targeted cellular domains may be modeled by artificial intelligence (AI) strategies that are inherently fluid, self-correcting, and adaptive at accommodating temporal changes in host defense mechanisms. An in-depth understanding of multiple self-correcting AIassociated viral processes will most certainly lead to novel therapeutic development platforms, notably the design of efficacious neuropharmacological agents to treat chronic CNS syndromes associated with long-COVID. In summary, it appears that viruses, notably SARS-CoV-2, are very much alive due to acquired genetic advantages that are intimately entrained to existential host processes via evolutionarily constrained AI-associated learning paradigms.
- MeSH
- COVID-19 * komplikace MeSH
- genomika MeSH
- lidé MeSH
- SARS-CoV-2 genetika MeSH
- strojové učení MeSH
- umělá inteligence MeSH
- viry * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Insulin-degrading enzyme (IDE) is a widely distributed Zn2+-binding metalloprotease that cleaves multiple short and medium-sized peptides prone to form β-structures. These include insulin and amyloid-β peptides. Accumulation and fibrillation of amyloid-β peptides leading to the formation of amyloid plaques is a characteristic sign of Alzheimer's disease (AD) pathology. OBJECTIVE: The study investigated the rs2421943 single nucleotide polymorphism (SNP) of the IDE gene as a risk factor for MCI (mild cognitive impairment) and AD. METHODS: Two independent groups of 1670 patients and controls were included. The AD group consisted of 595 patients and 400 controls; the MCI group involved 135 patients and 540 matched controls. PCR and restriction fragment length analysis were used to analyze the rs2421943 polymorphism. Using the miRBase and RNA22 prediction tools in silico indicated that the rs2421943 polymorphism is a potential target for a specific miRNA (hsa-miR-7110-5p). RESULTS: AG and GG genotypes of rs2421943 significantly increased the risk of AD, and the AG genotype increased the risk of MCI. It seems the G allele both increases the risk of AD and accelerates the transition through the MCI phase. In silico study revealed that rs2421943 is inside the sequence binding miRNA hsa-miR-7110-5p. The polymorphism could affect the rate of IDE pre-RNA (heterogeneous nuclear RNA, hnRNA) processing, resulting in slower translation, lower levels of IDE, deficient removal of amyloid-β fragments, and greater risk of and/or accelerated progression of AD. CONCLUSION: GG and AG genotypes of the single nucleotide polymorphism rs2421943 of insulindegrading enzyme gene increase the risk of AD and MCI.
INTRODUCTION: This study aims to identify levels of anxiety, depression, body weight, and levels of physical activity, as well as to verify possible associations among these variables in Brazilian adolescents. It is a cross-sectional study with a convenience sample of 291 Brazilian adolescents aged 13 to 15 years old (13.75±0.80 years old). METHODS: Researchers assessed students by filling out questionnaires of anxiety and depression symptoms, as well as the level of physical activity and checking anthropometric measures. Parametric and non-parametric statistics were used to compare groups divided by psychological, physical and overweight factors for boys and girls, adopting a significance level of 95%. RESULTS: Results showed higher waist circumference and physical activity levels for boys (p<0.01) and higher scores for anxiety and depressive symptoms questionnaires for girls (p<0.01). In addition, a low prevalence of depression was observed in boys (0.69%/CI0.03-4.36). For anxiety and depression variables in males and females with and without overweight and physically active and inactive, there were significant differences between groups (p < 0.05), but not within groups. CONCLUSION: The identification of a higher prevalence of girls with anxiety and depression was observed in this study and reinforced this information already demonstrated in the scientific literature. In general, the prevalence of depression was low in boys, while the prevalence of overweight, sedentary lifestyle, anxiety and depression were higher in girls.
- Publikační typ
- časopisecké články MeSH
One of the major global health care crises in the 21st century is antibiotic resistance. Almost all clinically used antibiotics have resistance emerging to them. Antibiotic Resistance can be regarded as the 'Faceless Pandemic' that has enthralled the entire world. It has become peremptory to develop treatment options as an alternative to antibiotic therapy for combating antibiotic-resistant pathogens. A clearer understanding of antibiotic resistance is required to prevent the rapid spread of antibiotic-resistant genes and the re-emergence of infections. The present review provides an insight into the different classifications and modes of action of antibiotics to understand how the hosts develop resistance to them. In addition, the association of genetics in the development of antibiotic resistance and environmental factors has also been discussed, emphasizing developing action plans to counter this "quiescent pandemic". It is also pertinent to create models that can predict the early resistance so that treatment strategies may build up in advance with the evolving resistance.
- MeSH
- antibakteriální látky * farmakologie terapeutické užití MeSH
- antibiotická rezistence MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
