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
Marine microorganisms represent virtually unlimited sources of novel biological compounds and can survive extreme conditions. Cellulases, a group of enzymes that are able to degrade cellulosic materials, are in high demand in various industrial and biotechnological applications, such as in the medical and pharmaceutical industries, food, fuel, agriculture, and single-cell protein, and as probiotics in aquaculture. The cellulosic biopolymer is a renewable resource and is a linearly arranged polysaccharide of glucose, with repeating units of disaccharide connected via β-1,4-glycosidic bonds, which are broken down by cellulase. A great deal of biodiversity resides in the ocean, and marine systems produce a wide range of distinct, new bioactive compounds that remain available but dormant for many years. The marine environment is filled with biomass from known and unknown vertebrates and invertebrate microorganisms, with much potential for use in medicine and biotechnology. Hence, complex polysaccharides derived from marine sources are a rich resource of microorganisms equipped with enzymes for polysaccharides degradation. Marine cellulases' extracts from the isolates are tested for their functional role in degrading seaweed and modifying wastes to low molecular fragments. They purify and renew environments by eliminating possible feedstocks of pollution. This review aims to examine the various types of marine cellulase producers and assess the ability of these microorganisms to produce these enzymes and their subsequent biotechnological applications.
Even though an association between inflammation and hypertension has been known for many years, it has not been simple to ascertain the role of several physiological responses involved. The innate immune response plays a critical role in these physiological responses. Innate immune cells can be activated directly by shear stress, activate the inflammasome and produce numerous cytokines and soluble mediators essential in hypertension. NFkB activation is mainly involved in the activation of innate immune cells. Shear stress also stimulates the expression of DAMP and PAMP receptors, enhancing pathogen and danger signals and magnifying inflammation. The adaptative immune response is activated with the increased antigen presentation resulting from the insults mentioned. Chronic inflammation may lead to autoimmunity. Peripheral hypoxia, a consequence of hypertension, activates hypoxia-inducing factors 1-α and 1-β (HIF-1α, HIF-1β), which modulate innate immune cells and promote inflammation. HIF-1α is involved in the upregulation of oxygen and nitrogen radical production proteins. HIF-1β down-regulates antioxidant enzymes. However, the critical evidence of the role of innate immune cells in hypertension came from the results of clinical trials involving therapies blocking inflammatory cytokines and Toll-like receptor expression. Several lines of research have been conducted on this complex disease. Pro-tolerogenic innate immune cells, myeloid suppressor cells, and M2 macrophages may play a crucial role in promoting or resolving inflammation, cardiovascular diseases and hypertension, and should be studied in detail.
- MeSH
- cytokiny metabolismus MeSH
- hypertenze * MeSH
- hypoxie MeSH
- lidé MeSH
- přirozená imunita * MeSH
- zánět metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
There are many situations of excessive production of reactive oxygen species (ROS) such as radiation, ischemia/reperfusion (I/R), and inflammation. ROS contribute to and arises from numerous cellular pathologies, diseases, and aging. ROS can cause direct deleterious effects by damaging proteins, lipids, and nucleic acids as well as exert detrimental effects on several cell signaling pathways. However, ROS are important in many cellular functions. The injurious effect of excessive ROS can hypothetically be mitigated by exogenous antioxidants, but clinically this intervention is often not favorable. In contrast, molecular hydrogen provides a variety of advantages for mitigating oxidative stress due to its unique physical and chemical properties. H2 may be superior to conventional antioxidants, since it can selectively reduce ●OH radicals while preserving important ROS that are otherwise used for normal cellular signaling. Additionally, H2 exerts many biological effects, including antioxidation, anti-inflammation, anti-apoptosis, and anti-shock. H2 accomplishes these effects by indirectly regulating signal transduction and gene expression, each of which involves multiple signaling pathways and crosstalk. The Keap1-Nrf2-ARE signaling pathway, which can be activated by H2, plays a critical role in regulating cellular redox balance, metabolism, and inducing adaptive responses against cellular stress. H2 also influences the crosstalk among the regulatory mechanisms of autophagy and apoptosis, which involve MAPKs, p53, Nrf2, NF-κB, p38 MAPK, mTOR, etc. The pleiotropic effects of molecular hydrogen on various proteins, molecules and signaling pathways can at least partly explain its almost universal pluripotent therapeutic potential.
- MeSH
- lidé MeSH
- revmatoidní artritida * farmakoterapie MeSH
- virové nemoci * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodníky MeSH
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that involves a pathological inflammatory response against articular cartilage in multiple joints throughout the body. It is a complex disorder associated with comorbidities such as depression, lymphoma, osteoporosis, and cardiovascular disease (CVD), which significantly deteriorate patients' quality of life and prognosis. This has ignited a large initiative to elucidate the physiopathology of RA, aiming to identify new therapeutic targets and approaches in its multidisciplinary management. Recently, various lipid bioactive products have been proposed to have an essential role in this process, including eicosanoids, specialized pro-resolving mediators, phospholipids/sphingolipids, and endocannabinoids. Dietary interventions using omega-3 polyunsaturated fatty acids or treatment with synthetic endocannabinoid agonists have been shown to significantly ameliorate RA symptoms. Indeed, the modulation of lipid metabolism may be crucial in the pathophysiology and treatment of autoimmune diseases.
- MeSH
- biologické přípravky * MeSH
- lidé MeSH
- racionální návrh léčiv * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodníky MeSH
Kidney transplantation is a preferable treatment of children with end-stage kidney disease. All kidney transplant recipients, including pediatric need immunosuppressive medications to prevent rejection episodes and graft loss. Induction therapy is used temporarily only immediately following transplantation while maintenance immunosuppressive drugs are started and given long-term. There is currently no consensus regarding the use of induction therapy in children; its use should be decided based on the immunological risk of the child. The recent progress shows that the recommended strategy is to use as maintenance immunosuppressive therapy a combination of a calcineurin inhibitor (preferably tacrolimus) with an antiproliferative drug (preferably mycophenolate mofetil) with steroids that can be withdrawn early or late in low-risk children. The mTOR-inhibitors (sirolimus, everolimus) are used rarely in pediatrics because of common side effects and no evidence of a benefit over calcineurin inhibitors. The use of calcineurin inhibitors, mycophenolate, and mTOR-inhibitors should be followed by therapeutic drug monitoring. Immunosuppressive therapy of acute rejection consists of high-dose steroids and/or anti-lymphocyte antibodies (T-cell mediated rejection) or plasma exchange, intravenous immunoglobulines and/or rituximab (antibodymediated rejection). The future strategies for research are mainly precise characterisation of children needing induction therapy, more specific indications for mTOR-inhibitors and for the far future, the possibility to reach the immuno tolerance.
- MeSH
- dítě MeSH
- imunosupresiva MeSH
- lidé MeSH
- pediatrie * MeSH
- rejekce štěpu farmakoterapie prevence a kontrola MeSH
- takrolimus MeSH
- transplantace ledvin * MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
No effective therapeutics to treat neurodegenerative diseases exist, despite significant attempts to find drugs that can reduce or rescue the debilitating symptoms of tauopathies such as Alzheimer's disease, Parkinson's disease, frontotemporal dementia, amyotrophic lateral sclerosis, or Pick's disease. A number of in vitro and in vivo models exist for studying neurodegenerative diseases, including cell models employing induced-pluripotent stem cells, cerebral organoids, and animal models of disease. Recent research has focused on microtubulestabilizing agents, either natural products or synthetic compounds that can prevent the axonal destruction caused by tau protein pathologies. Although promising results have come from animal model studies using brainpenetrant natural product microtubule-stabilizing agents, such as paclitaxel analogs that can access the brain, epothilones B and D, and other synthetic compounds such as davunetide or the triazolopyrimidines, early clinical trials in humans have been disappointing. This review aims to summarize the research that has been carried out in this area and discuss the potential for the future development of an effective microtubule stabilizing drug to treat neurodegenerative disease.
- MeSH
- Alzheimerova nemoc * farmakoterapie MeSH
- biologické přípravky * farmakologie MeSH
- lidé MeSH
- mikrotubuly MeSH
- neurodegenerativní nemoci * farmakoterapie MeSH
- proteiny tau MeSH
- tauopatie * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: Today, HIV-1 infection has become an extensive problem to public health and a greater challenge to all working researchers throughout the world. Since the beginning of HIV-1 virus, several antiviral therapeutic agents have been developed at various stages to combat HIV-1 infection. But, many of antiviral drugs are on the platform of drug resistance and toxicology issues, needs an urgent constructive investigation for the development of productive and protective therapeutics to make an improvement of individual life suffering with viral infection. As developing a novel agent is very costly, challenging and time taking route in the recent times. METHODS: The review summarized about the modern approaches of computational aided drug discovery to developing a novel inhibitor within a short period of time and less cost. RESULTS: The outcome suggests on the premise of reported information that the computational drug discovery is a powerful technology to design a defensive and fruitful therapeutic agents to combat HIV-1 infection and recover the lifespan of suffering one. CONCLUSION: Based on survey of the reported information, we concluded that the current computational approaches is highly supportive in the progress of drug discovery and controlling the viral infection.
