Publications by authors named "Jakub Rosik"

18 Publications

  • Page 1 of 1

Kidney damage from nonsteroidal anti-inflammatory drugs-Myth or truth? Review of selected literature.

Pharmacol Res Perspect 2021 Aug;9(4):e00817

Department of Pharmacokinetics and Monitored Therapy, Pomeranian Medical University, Szczecin, Poland.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely available drugs with anti-inflammatory and analgesic properties. Their mechanism of action is associated with the enzymes of the arachidonic acid cycle (cyclooxygenases: COX-1 and COX-2). The cyclooxygenase pathway results in the formation of prostanoids (prostaglandins [PGs], prostacyclins, and thromboxanes). It affects various structures of the human body, including the kidneys. Medical literature associates the usage of NSAIDs with acute kidney injury (AKI), tubulointerstitial nephritis (TIN), as well as nephrotic syndrome and chronic kidney disease (CKD). AKI associated with the chronic consumption of NSAIDs is mainly attributed to pharmacological polytherapy and the presence of cardiovascular or hepatic comorbidities. The pathomechanism of AKI and CKD is associated with inhibition of the biosynthesis of prostanoids involved in the maintenance of renal blood flow, especially PGE2 and PGI2. It is suggested that both COX isoforms play opposing roles in renal function, with natriuresis increased by COX-1 inhibition followed by a drop in a blood pressure, whereas COX-2 inhibition increases blood pressure and promotes sodium retention. TIN after NSAID use is potentially associated with glomerular basement membrane damage, reduction in pore size, and podocyte density. Therefore, nephrotic proteinuria and impairment of renal function may occur. The following article analyzes the association of NSAIDs with kidney disease based on available medical literature.
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http://dx.doi.org/10.1002/prp2.817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313037PMC
August 2021

The Role of CTLA4 and Its Polymorphisms in Solid Organ and Haematopoietic Stem Cell Transplantation.

Int J Mol Sci 2021 Mar 17;22(6). Epub 2021 Mar 17.

Pomeranian Medical University, Department of Physiology, al. Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland.

HLA matching, transplantation technique, or underlying disease greatly influences the probability of long-term transplantation success. It has been hypothesised that genetic variation affecting antigen presentation also contributes to the outcomes of both solid organ transplantation and allogeneic haematopoietic stem cell transplantation (AHSCT). Those genes, along with those responsible for innate and adaptive immunity, have become targets of investigation. In this review, we focus on the role of CTLA4 in the process of acute graft rejection and summarise the progress in our understanding of its role in predicting the outcome. We present the results of the latest studies investigating the link between gene variability and AHSCT, as well as organ transplantation outcomes. While some studies found a link between +49 A/G and -318 C/T and transplantation outcomes, comprehensive meta-analyses have failed to present any association. The most recent field reviews suggest that the -1772 T/C (rs733618) CC genotype is weakly associated with a lower risk of acute graft rejection, while +49 A/G might be clinically meaningful when investigated in the context of combinations with other polymorphisms. Studies verifying associations between 12 CTLA4 gene SNPs and AHSCT outcomes present inexplicit results. Some of the most commonly studied polymorphisms in this context include +49 A/G (rs231775) and CT60 A/G (rs3087243). The results signify that, in order to understand the role of CTLA4 and its gene polymorphisms in transplantology, further studies must be conducted.
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http://dx.doi.org/10.3390/ijms22063081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002677PMC
March 2021

Role of PFKFB3 and PFKFB4 in Cancer: Genetic Basis, Impact on Disease Development/Progression, and Potential as Therapeutic Targets.

Cancers (Basel) 2021 Feb 22;13(4). Epub 2021 Feb 22.

Department of Histology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland.

Glycolysis is a crucial metabolic process in rapidly proliferating cells such as cancer cells. Phosphofructokinase-1 (PFK-1) is a key rate-limiting enzyme of glycolysis. Its efficiency is allosterically regulated by numerous substances occurring in the cytoplasm. However, the most potent regulator of PFK-1 is fructose-2,6-bisphosphate (F-2,6-BP), the level of which is strongly associated with 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase activity (PFK-2/FBPase-2, PFKFB). PFK-2/FBPase-2 is a bifunctional enzyme responsible for F-2,6-BP synthesis and degradation. Four isozymes of PFKFB (PFKFB1, PFKFB2, PFKFB3, and PFKFB4) have been identified. Alterations in the levels of all PFK-2/FBPase-2 isozymes have been reported in different diseases. However, most recent studies have focused on an increased expression of PFKFB3 and PFKFB4 in cancer tissues and their role in carcinogenesis. In this review, we summarize our current knowledge on all PFKFB genes and protein structures, and emphasize important differences between the isoenzymes, which likely affect their kinase/phosphatase activities. The main focus is on the latest reports in this field of cancer research, and in particular the impact of PFKFB3 and PFKFB4 on tumor progression, metastasis, angiogenesis, and autophagy. We also present the most recent achievements in the development of new drugs targeting these isozymes. Finally, we discuss potential combination therapies using PFKFB3 inhibitors, which may represent important future cancer treatment options.
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http://dx.doi.org/10.3390/cancers13040909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926708PMC
February 2021

Pleiotropic effects of statins: A focus on cancer.

Biochim Biophys Acta Mol Basis Dis 2020 12 12;1866(12):165968. Epub 2020 Sep 12.

Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada; Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran; Research Institute of Oncology and Hematology, Cancer Care Manitoba, University of Manitoba, Winnipeg, Canada. Electronic address:

The statin drugs ('statins') potently inhibit hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase by competitively blocking the active site of the enzyme. Statins decrease de novo cholesterol biosynthesis and thereby reduce plasma cholesterol levels. Statins exhibit "pleiotropic" properties that are independent of their lipid-lowering effects. For example, preclinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. Furthermore, statins show chemo-sensitizing effects by impairing Ras family GTPase signaling. However, whether statins have clinically meaningful anti-cancer effects remains an area of active investigation. Both preclinical and clinical studies on the potential mechanisms of action of statins in several cancers have been reviewed in the literature. Considering the contradictory data on their efficacy, we present an up-to-date summary of the pleiotropic effects of statins in cancer therapy and review their impact on different malignancies. We also discuss the synergistic anti-cancer effects of statins when combined with other more conventional anti-cancer drugs to highlight areas of potential therapeutic development.
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http://dx.doi.org/10.1016/j.bbadis.2020.165968DOI Listing
December 2020

COVID-19: The Influence of ACE Genotype and ACE-I and ARBs on the Course of SARS-CoV-2 Infection in Elderly Patients.

Clin Interv Aging 2020 21;15:1231-1240. Epub 2020 Jul 21.

Department of Anaesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University in Szczecin, Szczecin, Poland.

Since the beginning of 2020, the whole world has been struggling with the pandemic of Coronavirus Disease 2019 (COVID-19) caused by a novel coronavirus SARS-CoV-2. The SARS-CoV-2 infection depends on ACE2, TMPRSS2, and CD147, which are expressed on host cells. Several studies suggest that some single nucleotide polymorphisms (SNPs) of ACE2 might be a risk factor of COVID-19 infection. Genotypes affect ACE2 structure, its serum concentration, and levels of circulating angiotensin (1-7). Moreover, there is evidence that ACE genotype affects the outcomes of acute respiratory distress syndrome (ARDS) treatment, the most severe consequence of SARS-CoV-2 infection. COVID-19 morbidity, infection course, and mortality might depend on ACE D allele frequency. The aim of this narrative review was to analyze and identify the mechanisms of ACE-I and ARBs with particular emphasis on angiotensin receptors and their polymorphism in the light of COVID-19 pandemic as these medications are commonly prescribed to elderly patients. There is no direct evidence yet for ACE-I or ARBs in the treatment of COVID-19. However, for those already taking these medications, both the European Society of Cardiology and the American College of Cardiology recommend continuing the treatment, because at present, there is no clear clinical or scientific evidence to justify the discontinuation of ACE-I or ARBs. Individualized treatment decisions should be based on the clinical condition and co-morbidities of each patient.
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http://dx.doi.org/10.2147/CIA.S261516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382582PMC
August 2020

FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy.

Drug Resist Updat 2020 12 15;53:100719. Epub 2020 Jul 15.

Biotechnology Centre, Silesian University of Technology, Krzywoustego 8 Str., 44-100, Gliwice, Poland. Electronic address:

In December 2019, a novel SARS-CoV-2 coronavirus emerged, causing an outbreak of life-threatening pneumonia in the Hubei province, China, and has now spread worldwide, causing a pandemic. The urgent need to control the disease, combined with the lack of specific and effective treatment modalities, call for the use of FDA-approved agents that have shown efficacy against similar pathogens. Chloroquine, remdesivir, lopinavir/ritonavir or ribavirin have all been successful in inhibiting SARS-CoV-2 in vitro. The initial results of a number of clinical trials involving various protocols of administration of chloroquine or hydroxychloroquine mostly point towards their beneficial effect. However, they may not be effective in cases with persistently high viremia, while results on ivermectin (another antiparasitic agent) are not yet available. Interestingly, azithromycin, a macrolide antibiotic in combination with hydroxychloroquine, might yield clinical benefit as an adjunctive. The results of clinical trials point to the potential clinical efficacy of antivirals, especially remdesivir (GS-5734), lopinavir/ritonavir, and favipiravir. Other therapeutic options that are being explored involve meplazumab, tocilizumab, and interferon type 1. We discuss a number of other drugs that are currently in clinical trials, whose results are not yet available, and in various instances we enrich such efficacy analysis by invoking historic data on the treatment of SARS, MERS, influenza, or in vitro studies. Meanwhile, scientists worldwide are seeking to discover novel drugs that take advantage of the molecular structure of the virus, its intracellular life cycle that probably elucidates unfolded-protein response, as well as its mechanism of surface binding and cell invasion, like angiotensin converting enzymes-, HR1, and metalloproteinase inhibitors.
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http://dx.doi.org/10.1016/j.drup.2020.100719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362818PMC
December 2020

COVID-19: Pain Management in Patients with SARS-CoV-2 Infection-Molecular Mechanisms, Challenges, and Perspectives.

Brain Sci 2020 Jul 20;10(7). Epub 2020 Jul 20.

Department of Anesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland.

Since the end of 2019, the whole world has been struggling with the pandemic of the new Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). Available evidence suggests that pain is a common symptom during Coronavirus Disease 2019 (COVID-19). According to the World Health Organization, many patients suffer from muscle pain (myalgia) and/or joint pain (arthralgia), sore throat and headache. The exact mechanisms of headache and myalgia during viral infection are still unknown. Moreover, many patients with respiratory failure get admitted to the intensive care unit (ICU) for ventilatory support. Pain in ICU patients can be associated with viral disease itself (myalgia, arthralgia, peripheral neuropathies), may be caused by continuous pain and discomfort associated with ICU treatment, intermittent procedural pain and chronic pain present before admission to the ICU. Undertreatment of pain, especially when sedation and neuromuscular blocking agents are used, prone positioning during mechanical ventilation or extracorporeal membrane oxygenation (ECMO) may trigger delirium and cause peripheral neuropathies. This narrative review summarizes current knowledge regarding challenges associated with pain assessment and management in COVID-19 patients. A structured prospective evaluation should be undertaken to analyze the probability, severity, sources and adequate treatment of pain in patients with COVID-19 infection.
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http://dx.doi.org/10.3390/brainsci10070465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407489PMC
July 2020

COVID-19: The Potential Treatment of Pulmonary Fibrosis Associated with SARS-CoV-2 Infection.

J Clin Med 2020 Jun 19;9(6). Epub 2020 Jun 19.

Department of Anaesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University, 70-111 Szczecin, Poland.

In December 2019, a novel coronavirus, SARS-CoV-2, appeared, causing a wide range of symptoms, mainly respiratory infection. In March 2020, the World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a pandemic, therefore the efforts of scientists around the world are focused on finding the right treatment and vaccine for the novel disease. COVID-19 has spread rapidly over several months, affecting patients across all age groups and geographic areas. The disease has a diverse course; patients may range from asymptomatic to those with respiratory failure, complicated by acute respiratory distress syndrome (ARDS). One possible complication of pulmonary involvement in COVID-19 is pulmonary fibrosis, which leads to chronic breathing difficulties, long-term disability and affects patients' quality of life. There are no specific mechanisms that lead to this phenomenon in COVID-19, but some information arises from previous severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) epidemics. The aim of this narrative review is to present the possible causes and pathophysiology of pulmonary fibrosis associated with COVID-19 based on the mechanisms of the immune response, to suggest possible ways of prevention and treatment.
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http://dx.doi.org/10.3390/jcm9061917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356800PMC
June 2020

Reprogramming and transdifferentiation - two key processes for regenerative medicine.

Eur J Pharmacol 2020 Sep 18;882:173202. Epub 2020 Jun 18.

Department of Pathology, Pomeranian Medical University, Szczecin, Poland.

Regenerative medicine based on transplants obtained from donors or foetal and new-born mesenchymal stem cells, encounter important obstacles such as limited availability of organs, ethical issues and immune rejection. The growing demand for therapeutic methods for patients being treated after serious accidents, severe organ dysfunction and an increasing number of cancer surgeries, exceeds the possibilities of the therapies that are currently available. Reprogramming and transdifferentiation provide powerful bioengineering tools. Both procedures are based on the somatic differentiated cells, which are easily and unlimitedly available, like for example: fibroblasts. During the reprogramming procedure mature cells are converted into pluripotent cells - which are capable to differentiate into almost any kind of desired cells. Transdifferentiation directly converts differentiated cells of one type into another differentiated cells type. Both procedures allow to obtained patient's dedicated cells for therapeutic purpose in regenerative medicine. In combination with biomaterials, it is possible to obtain even whole anatomical structures. Those patient's dedicated structures may serve for them upon serious accidents with massive tissue damage but also upon cancer surgeries as a replacement of damaged organ. Detailed information about reprogramming and transdifferentiation procedures as well as the current state of the art are presented in our review.
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http://dx.doi.org/10.1016/j.ejphar.2020.173202DOI Listing
September 2020

Using pharmacogenetics to predict methotrexate response in rheumatoid arthritis patients.

Expert Opin Drug Metab Toxicol 2020 Jul 19;16(7):617-626. Epub 2020 Jun 19.

Department of Physiology, Pomeranian Medical University , Szczecin, Poland.

Introduction: Methotrexate (MTX) is a folate antagonist and a first-line drug for the treatment of rheumatoid arthritis (RA). However, in up to 30% of cases, MTX monotherapy is insufficient, while a further 30% of patients suffer with severe adverse effects. Despite extensive clinical evidence, it is not currently possible to predict therapy outcomes and drug toxicity for MTX. Therefore, to establish biomarkers of toxicity and successful disease remission, pharmacogenomic approaches are rapidly becoming more popular.

Areas: This review summarizes recent pharmacogenomic studies evaluating MTX efficacy and toxicity. In recent years, multiple genetic alterations associated with MTX therapy outcomes and toxicity have been identified in genes associated with MTX metabolism and effector pathways. However, the data are inconsistent and require further validation.

Expert Opinion: To date, several single nucleotide polymorphisms (SNPs) have been linked with MTX efficacy. However, thanks to equivocal data, pharmacogenomic testing in routine clinical practice remains a distant prospect. Genome-wide association studies (GWAS) could facilitate the evaluation of current SNPs, and support searches for new genetic variations Once achieved, only then will it be possible to introduce more personalized and individualized therapies for RA patients.
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http://dx.doi.org/10.1080/17425255.2020.1777279DOI Listing
July 2020

Aspirin and its pleiotropic application.

Eur J Pharmacol 2020 Jan 26;866:172762. Epub 2019 Oct 26.

Department of Pathology, Pomeranian Medical University, Szczecin, Poland.

Aspirin (acetylsalicylic acid), the oldest synthetic drug, was originally used as an anti-inflammatory medication. Being an irreversible inhibitor of COX (prostaglandin-endoperoxide synthase) enzymes that produce precursors for prostaglandins and thromboxanes, it has gradually found several other applications. Sometimes these applications are unrelated to its original purpose for example its use as an anticoagulant. Applications such as these have opened opportunities for new treatments. In this case, it has been tested in patients with cardiovascular disease to reduce the risk of myocardial infarct. Its function as an anticoagulant has also been explored in the prophylaxis and treatment of pre-eclampsia, where due to its anti-inflammatory properties, aspirin intake may be used to reduce the risk of colorectal cancer. It is important to always consider both the risks and benefits of aspirin's application. This is especially important for proposed use in the prevention and treatment of neurologic ailments like Alzheimer's disease, or in the prophylaxis of myocardial infarct. In such cases, the decision if aspirin should be applied, and at what dose may be guided by specific molecular markers. In this revived paper, the pleiotropic application of aspirin is summarized.
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http://dx.doi.org/10.1016/j.ejphar.2019.172762DOI Listing
January 2020

The evolution in our understanding of the genetics of rheumatoid arthritis and the impact on novel drug discovery.

Expert Opin Drug Discov 2020 01 29;15(1):85-99. Epub 2019 Oct 29.

Department of Physiology, Pomeranian Medical University, Szczecin, Poland.

: Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by chronic inflammation of the joints and affects 1% of the population. Polymorphisms of genes that encode proteins that primarily participate in inflammation may influence RA occurrence or become useful biomarkers for certain types of anti-rheumatic treatment.: The authors summarize the recent progress in our understanding of the genetics of RA. In the last few years, multiple variants of genes that are associated with RA risk have been identified. The development of new technologies and the detection of new potential therapeutic targets that contribute to novel drug discovery are also described.: There is still the need to search for new genes which may be a potential target for RA therapy. The challenge is to develop appropriate strategies for achieving insight into the molecular pathways involved in RA pathogenesis. Understanding the genetics, immunogenetics, epigenetics and immunology of RA could help to identify new targets for RA therapy. The development of new technologies has enabled the detection of a number of new genes, particularly genes associated with proinflammatory cytokines and chemokines, B- and T-cell activation pathways, signal transducers and transcriptional activators, which might be potential therapeutic targets in RA.
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http://dx.doi.org/10.1080/17460441.2020.1682992DOI Listing
January 2020

Umbilical cord blood transplantation and the impact of the CTLA4 genotype on outcomes.

Expert Rev Hematol 2019 12 30;12(12):1089-1094. Epub 2019 Oct 30.

Department of Physiology, Pomeranian Medical University, Szczecin, Poland.

: Umbilical cord blood transplantation is an effective method of curing multiple diseases when there is no donor available for allogeneic hematopoietic stem cell transplantation (AHSCT). It has been recently suggested that polymorphisms in genes affecting antigen presentation could potentially affect cord blood transplantation (CBT) outcomes.: In this review, we present the results of the latest studies investigating the link between gene variability and umbilical cord blood transplantation outcomes.: The search for genetic variants that influence the immune response, both innate and adaptive immunity, may lead to more optimal therapies. Promising candidate genes are those that regulate the expression of proteins associated with T-cell activation. Many genetic variants could be therapeutically important, including those related to innate and adaptive immunity, cytokines, chemokines, drug-metabolizing enzymes, drug transporters, and inflammatory enzymes. The development of an algorithm that includes the determination of selected genetic variants could be helpful for an appropriate donor-recipient CBT matching.
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http://dx.doi.org/10.1080/17474086.2019.1680281DOI Listing
December 2019

The role of genetics and epigenetics in the pathogenesis of gestational diabetes mellitus.

Ann Hum Genet 2020 03 1;84(2):114-124. Epub 2019 Oct 1.

Department of Physiology, Pomeranian Medical University, Szczecin, Poland.

Diabetes mellitus (DM) is a heterogeneous group of disorders whose common trait is chronic hyperglycemia. Gestational diabetes mellitus (GDM) is one of the subtypes of DM that manifests during pregnancy. It is believed that 2%-5% of pregnancies worldwide are complicated with GDM, with the prevalence having significantly increased over the last decade. While the pathogenesis of the disease remains largely unknown, GDM is believed to be a result of interactions between genetic, epigenetic, and environmental factors. Linkage and association studies, including those that are genome-wide, have allowed us to identify complex genetic and epigenetic mechanisms that lead to the development of GDM. Multiple common variants in candidate genes such as potassium inwardly rectifying channel subfamily J, member 11 (KCNJ11), glucokinase (GCK), or hepatocyte nuclear factor 1α (HNF1A) have been found to increase the disease risk. In this review, we provide a detailed overview of the current knowledge concerning the influence of genetics and epigenetics on the development of GDM.
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http://dx.doi.org/10.1111/ahg.12356DOI Listing
March 2020

Betulin and its derivatives as novel compounds with different pharmacological effects.

Biotechnol Adv 2020 Jan - Feb;38:107409. Epub 2019 Jun 18.

Department of Human Anatomy and Cell Science, Rady College of Medicine, Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Biology of Breathing Theme, Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada; Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran; Research Institute of Oncology and Hematology, CancerCare Manitoba, University of Manitoba, Winnipeg, Canada. Electronic address:

Betulin (B) and Betulinic acid (BA) are natural pentacyclic lupane-structure triterpenoids which possess a wide range of pharmacological activities. Recent evidence indicates that B and BA have several properties useful for the treatment of metabolic disorders, infectious diseases, cardiovascular disorders, and neurological disorders. In the current review, we discuss B and BA structures and derivatives and then comprehensively explain their pharmacological effects in relation to various diseases. We also explain antiviral, antibacterial and anti-cancer effects of B and BA. Finally, we discuss the delivery methods, in which these compounds most effectively target different systems.
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http://dx.doi.org/10.1016/j.biotechadv.2019.06.008DOI Listing
February 2020

New therapies for the treatment of heart failure: a summary of recent accomplishments.

Ther Clin Risk Manag 2019 22;15:147-155. Epub 2019 Jan 22.

Department of Physiology, Pomeranian Medical University, Szczecin, Poland,

Despite continuous efforts to prevent cardiovascular diseases (CVDs), heart failure prevails as the number one cause of death in developed countries. To properly treat CVDs, scientists had to take a closer look at the factors that contribute to their pathogenesis and either modernize current pharmaceuticals or develop brand new treatments. Enhancement of current drugs, such as tolvaptan and omecamtiv mecarbil, sheds new light on already-known therapies. Tolvaptan, a vasopressin antagonist, could be adopted in heart failure therapy as it reduces pre- and afterload by decreasing systolic blood pressure and blood volume. Omecamtiv mecarbil, which is a myosin binding peptide, could aid cardiac contractility. The next generation vasodilators, serelaxin and ularitide, are based on naturally occurring peptides and they reduce peripheral vascular resistance and increase the cardiac index. In combination with their anti-inflammatory properties, they could turn out to be extremely potent drugs for heart failure treatment. Cardiotrophin has exceeded many researchers' expectations, as evidence suggests that it could cause sarcomere hypertrophy without excessive proliferation of connective tissue. Rapid progress in gene therapy has caused it to finally be considered as one of the viable options for the treatment of CVDs. This novel therapeutic approach could restore stable heart function either by restoring depleted membrane proteins or by balancing the intracellular calcium concentration. Although it has been set back by problems concerning its long-term effects, it is still highly likely to succeed.
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http://dx.doi.org/10.2147/TCRM.S179302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348963PMC
January 2019

CTLA4 antagonists in phase I and phase II clinical trials, current status  and  future perspectives for cancer therapy.

Expert Opin Investig Drugs 2019 02 30;28(2):149-159. Epub 2018 Dec 30.

a Department of Physiology , Pomeranian Medical University , Szczecin , Poland.

Introduction: In cancer, the immune response to tumor antigens is often suppressed by inhibitors and ligands. Checkpoint blockade, considered one of the most promising frontiers for anti-cancer therapy, aims to stimulate the immune anti-cancer response. Agents such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors offer prolonged survival with manageable side effects.

Areas Covered: We summarize the recent clinical successes of CTLA-4 inhibitors and place a strong emphasis on those in early phase clinical trials, often in combination with other immune check-point inhibitors, i.e., programmed cell death protein 1 (PD-1) and BRAF/mitogen-activated protein kinase inhibitors.

Expert Opinion: Recent phase I and phase II clinical trials confirm the efficacy of anti-CTLA-4 therapy for treatment of cancers such as renal cell carcinoma. These studies also indicated increased efficacy with combined immune checkpoint blockade with PD-1 or Ras/Raf/mitogen-activated protein kinase/ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK) inhibitors. Researchers must search for new immune targets that may enable more effective and safe immune checkpoint blockade and cancer therapy. This goal may be achieved by next-generation combination therapies to overcome immune checkpoint therapy resistance.
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http://dx.doi.org/10.1080/13543784.2019.1559297DOI Listing
February 2019

Potential targets of gene therapy in the treatment of heart failure.

Expert Opin Ther Targets 2018 09;22(9):811-816

a Department of Physiology , Pomeranian Medical University , Szczecin , Poland.

Introduction: Heart failure (HF) is one of the most prevalent diseases; it affects millions of people every year. In addition to being one of the major causes of mortality, it generates a financial burden on healthcare systems. Despite progress in developing new pharmaceuticals intended to treat HF, even the newest therapies are not satisfactory. Ischemic heart disease often requires operational treatment which decreases the patient's quality of life. The emergence of gene therapy as a viable treatment option for monogenic disorders has resulted in the approach becoming a topic of study in cardiology. Areas covered: The identification of molecular targets could enable a new form of treatment for HF. This review discusses the current advances related to the implementation of gene therapy for those genes connected to the regulation of calcium concentrations. Several trials have recently investigated the efficacy of gene therapy in HF treatment. Researchers have identified SERCA2a, S100A1 and IPP-1 as potential therapeutic targets. Another therapeutic approach could relate to the gene expression regulatory process called SUMOylation.

Commentary: Researchers still face a long road ahead; however, overcoming several significant problems will likely lead to a greatly improved prognosis in many patients.
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http://dx.doi.org/10.1080/14728222.2018.1514012DOI Listing
September 2018
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