Browsing by Author "Jansons, Juris"
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Item Alphavirus‐driven interferon gamma (IFNG) expression inhibits tumor growth in orthotopic 4T1 breast cancer model(2021-11) Trofimova, Olga; Korotkaja, Ksenija; Skrastina, Dace; Jansons, Juris; Spunde, Karina; Isaguliants, Maria; Zajakina, Anna; Institute of Microbiology and VirologyInterferon gamma (IFNg) is a pleiotropic cytokine that can potentially reprogram the tumor microenvironment; however, the antitumor immunomodulatory properties of IFNg still need to be validated due to variable therapeutic outcomes in preclinical and clinical studies. We developed a replication‐deficient Semliki Forest virus vector expressing IFNg (SFV/IFNg) and evaluated its immunomodulatory antitumor potential in vitro in a model of 3D spheroids and in vivo in an immunocompetent 4T1 mouse breast cancer model. We demonstrated that SFV‐derived, IFN‐g‐stimulated bone marrow macrophages can be used to acquire the tumoricidal M1 phenotype in 3D nonattached conditions. Coculturing SFV/IFNg‐infected 4T1 spheroids with BMDMs inhibited spheroid growth. In the orthotopic 4T1 mouse model, intratumoral administration of SFV/IFNg virus particles alone or in combination with the Pam3CSK4 TLR2/1 ligand led to significant inhibition of tumor growth compared to the administration of the control SFV/Luc virus particles. Analysis of the composition of intratumoral lymphoid cells isolated from tumors after SFV/IFNg treatment revealed increased CD4+ and CD8+ and decreased T‐reg (CD4+/CD25+/FoxP3+) cell populations. Furthermore, a significant decrease in the populations of cells bearing myeloid cell markers CD11b, CD38, and CD206 was observed. In conclusion, the SFV/IFNg vector induces a therapeutic antitumor T‐cell response and inhibits myeloid cell infiltration in treated tumors.Item Cellular immune response induced by dna immunization of mice with drug resistant integrases of hiv-1 clade a offers partial protection against growth and metastatic activity of integrase-expressing adenocarcinoma cells(2021-06) Isaguliants, Maria; Krotova, Olga; Petkov, Stefan; Jansons, Juris; Bayurova, Ekaterina; Mezale, Dzeina; Fridrihsone, Ilze; Kilpelainen, Athina; Podschwadt, Philip; Agapkina, Yulia; Smirnova, Olga; Kostic, Linda; Saleem, Mina; Latyshev, Oleg; Eliseeva, Olesja; Malkova, Anastasia; Gorodnicheva, Tatiana; Wahren, Britta; Gordeychuk, Ilya; Starodubova, Elizaveta; Latanova, Anastasia; Research DepartmentTherapeutic DNA-vaccination against drug-resistant HIV-1 may hinder emergence and spread of drug-resistant HIV-1, allowing for longer successful antiretroviral treatment (ART) up-to relief of ART. We designed DNA-vaccines against drug-resistant HIV-1 based on consensus clade A integrase (IN) resistant to raltegravir: IN_in_r1 (L74M/E92Q/V151I/N155H/G163R) or IN_in_r2 (E138K/G140S/Q148K) carrying D64V abrogating IN activity. INs, overexpressed in mammalian cells from synthetic genes, were assessed for stability, route of proteolytic degradation, and ability to induce oxidative stress. Both were found safe in immunotoxicity tests in mice, with no inherent carcinogenicity: their expression did not enhance tumorigenic or metastatic potential of adenocarcinoma 4T1 cells. DNA-immunization of mice with INs induced potent multicytokine T-cell response mainly against aa 209–239, and moderate IgG response cross-recognizing diverse IN variants. DNA-immunization with IN_in_r1 protected 60% of mice from challenge with 4Tlluc2 cells expressing non-mutated IN, while DNA-immunization with IN_in_r2 protected only 20% of mice, although tumor cells expressed IN matching the immunogen. Tumor size inversely correlated with IN-specific IFN-γ/IL-2 T-cell response. IN-expressing tumors displayed compromised metastatic activity restricted to lungs with reduced metastases size. Protective potential of IN immunogens relied on their immunogenicity for CD8+ T-cells, dependent on proteasomal processing and low level of oxidative stress.Item Comparative Immunogenicity in Rabbits of the Polypeptides Encoded by the 5′ Terminus of Hepatitis C Virus RNA(2015) Sominskaya, Irina; Jansons, Juris; Dovbenko, Anastasija; Petrakova, Natalia; Lieknina, Ilva; Mihailova, Marija; Latyshev, Oleg; Eliseeva, Olesja; Stahovska, Irina; Akopjana, Inara; Petrovskis, Ivars; Isaguliants, Maria; Rīga Stradiņš UniversityRecent studies on the primate protection from HCV infection stressed the importance of immune response against structural viral proteins. Strong immune response against nucleocapsid (core) protein was difficult to achieve, requesting further experimentation in large animals. Here, we analyzed the immunogenicity of core aa 1-173, 1-152, and 147-191 and of its main alternative reading frame product F-protein in rabbits. Core aa 147-191 was synthesized; other polypeptides were obtained by expression in E. coli. Rabbits were immunized by polypeptide primes followed by multiple boosts and screened for specific anti-protein and anti-peptide antibodies. Antibody titers to core aa 147-191 reached 105; core aa 1-152, 5 × 105; core aa 1-173 and F-protein, 106. Strong immunogenicity of the last two proteins indicated that they may compete for the induction of immune response. The C-terminally truncated core was also weakly immunogenic on the T-cell level. To enhance core-specific cellular response, we immunized rabbits with the core aa 1-152 gene forbidding F-protein formation. Repeated DNA immunization induced a weak antibody and sustained proliferative response of broad specificity confirming a gain of cellular immunogenicity. Epitopes recognized in rabbits overlapped those in HCV infection. Our data promotes the use of rabbits for the immunogenicity tests of prototype HCV vaccines.Item Effects of urinary extracellular vesicles from prostate cancer patients on the transcriptomes of cancer-associated and normal fibroblasts(2022-12) Sadovska, Lilite; Zayakin, Pawel; Bajo-Santos, Cristina; Endzeliņš, Edgars; Auders, Jānis; Keiša, Laura; Jansons, Juris; Lietuvietis, Vilnis; Linē, Aija; Rīga Stradiņš UniversityBackground: Increasing evidence suggests that cancer-derived extracellular vesicles (EVs) alter the phenotype and functions of fibroblasts and trigger the reprogramming of normal fibroblasts into cancer-associated fibroblasts (CAFs). Here, we for the first time studied the effects of urinary EVs from PC patients and healthy males on the transcriptional landscape of prostate CAFs and normal foreskin fibroblasts. Methods: Patient-derived prostate fibroblast primary cultures PCF-54 and PCF-55 were established from two specimens of PC tissues. EVs were isolated from urine samples of 3 patients with PC and 2 healthy males and used for the treatment of prostate fibroblast primary cultures and normal foreskin fibroblasts. The EV-treated fibroblasts were subjected to RNA sequencing analysis. Results: RNA sequencing analysis showed that the fibroblast cultures differed significantly in their response to urinary EVs. The transcriptional response of foreskin fibroblasts to the urinary EVs isolated from PC patients and healthy controls was very similar and mostly related to the normal functions of fibroblasts. On the contrary, PCF-54 cells responded very differently - EVs from PC patients elicited transcriptional changes related to the regulation of the cell division and chromosome segregation, whereas EVs from healthy males affected mitochondrial respiration. In PCF-55 cells, EVs from both, PC-patients and controls induced the expression of a number of chemokines such as CCL2, CCL13, CXCL1, CXCL8, whereas pathways related to regulation of apoptotic signaling and production of cell adhesion molecules were triggered specifically by EVs from PC patients. Conclusion: This study demonstrates that urinary EVs from PC patients and healthy controls elicit distinct transcriptional responses in prostate CAFs and supports the idea that EVs contribute to the generation of functional heterogeneity of CAFs. Moreover, this study suggests that the changes in the gene expression pattern in EV recipient cells might serve as a novel type of functional cancer biomarkers.Item HIV-1 Protease as DNA Immunogen against Drug Resistance in HIV-1 Infection : DNA Immunization with Drug Resistant HIV-1 Protease Protects Mice from Challenge with Protease-Expressing Cells(2023-01) Petkov, Stefan; Kilpeläinen, Athina; Bayurova, Ekaterina; Latanova, Anastasia; Mezale, Dzeina; Fridrihsone, Ilse; Starodubova, Elizaveta; Jansons, Juris; Dudorova, Alesja; Gordeychuk, Ilya; Wahren, Britta; Isaguliants, Maria; Research DepartmentDNA immunization with HIV-1 protease (PR) is advanced for immunotherapy of HIV-1 infection to reduce the number of infected cells producing drug-resistant virus. A consensus PR of the HIV-1 FSU_A strain was designed, expression-optimized, inactivated (D25N), and supplemented with drug resistance (DR) mutations M46I, I54V, and V82A common for FSU_A. PR variants with D25N/M46I/I54V (PR_Ai2mut) and with D25N/M46I/I54V/V82A (PR_Ai3mut) were cloned into the DNA vaccine vector pVAX1, and PR_Ai3mut, into a lentiviral vector for the transduction of murine mammary adenocarcinoma cells expressing luciferase 4T1luc2. BALB/c mice were DNA-immunized by intradermal injections of PR_Ai, PR_Ai2mut, PR_Ai3mut, vector pVAX1, or PBS with electroporation. All PR variants induced specific CD8+ T-cell responses revealed after splenocyte stimulation with PR-derived peptides. Splenocytes of mice DNA-immunized with PR_Ai and PR_Ai2mut were not activated by peptides carrying V82A, whereas splenocytes of PR_Ai3mut-immunized mice recognized both peptides with and without V82A mutation. Mutations M46I and I54V were immunologically silent. In the challenge study, DNA immunization with PR_Ai3mut protected mice from the outgrowth of subcutaneously implanted adenocarcinoma 4T1luc2 cells expressing PR_Ai3mut; a tumor was formed only in 1/10 implantation sites and no metastases were detected. Immunizations with other PR variants were not protective; all mice formed tumors and multiple metastasis in the lungs, liver, and spleen. CD8+ cells of PR_Ai3mut DNA-immunized mice exhibited strong IFN-γ/IL-2 responses against PR peptides, while the splenocytes of mice in other groups were nonresponsive. Thus, immunization with a DNA plasmid encoding inactive HIV-1 protease with DR mutations suppressed the growth and metastatic activity of tumor cells expressing PR identical to the one encoded by the immunogen. This demonstrates the capacity of T-cell response induced by DNA immunization to recognize single DR mutations, and supports the concept of the development of immunotherapies against drug resistance in HIV-1 infection. It also suggests that HIV-1-infected patients developing drug resistance may have a reduced natural immune response against DR HIV-1 mutations causing an immune escape.Item HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist(2019-12-02) Bayurova, Ekaterina; Jansons, Juris; Skrastina, Dace; Smirnova, Olga; Mezale, Dzeina; Kostyusheva, Anastasia; Kostyushev, Dmitry; Petkov, Stefan; Podschwadt, Philip; Valuev-Elliston, Vladimir; Sasinovich, Sviataslau; Korolev, Sergey; Warholm, Per; Latanova, Anastasia; Starodubova, Elizaveta; Tukhvatulin, Amir; Latyshev, Oleg; Selimov, Renat; Metalnikov, Pavel; Komarov, Alexander; Ivanova, Olga; Gorodnicheva, Tatiana; Kochetkov, Sergey; Gottikh, Marina; Strumfa, Ilze; Ivanov, Alexander; Gordeychuk, Ilya; Isaguliants, Maria; Department of Pathology; Rīga Stradiņš UniversityHIV-induced immune suppression results in the high prevalence of HIV/AIDS-associated malignancies including Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer. HIV-infected people are also at an increased risk of "non-AIDS-defining" malignancies not directly linked to immune suppression but associated with viral infections. Their incidence is increasing despite successful antiretroviral therapy. The mechanism behind this phenomenon remains unclear. Here, we obtained daughter clones of murine mammary gland adenocarcinoma 4T1luc2 cells expressing consensus reverse transcriptase of HIV-1 subtype A FSU_A strain (RT_A) with and without primary mutations of drug resistance. In in vitro tests, mutations of resistance to nucleoside inhibitors K65R/M184V reduced the polymerase, and to nonnucleoside inhibitors K103N/G190S, the RNase H activities of RT_A. Expression of these RT_A variants in 4T1luc2 cells led to increased production of the reactive oxygen species (ROS), lipid peroxidation, enhanced cell motility in the wound healing assay, and upregulation of expression of Vimentin and Twist. These properties, particularly, the expression of Twist, correlated with the levels of expression RT_A and/or the production of ROS. When implanted into syngeneic BALB/C mice, 4T1luc2 cells expressing nonmutated RT_A demonstrated enhanced rate of tumor growth and increased metastatic activity, dependent on the level of expression of RT_A and Twist. No enhancement was observed for the clones expressing mutated RT_A variants. Plausible mechanisms are discussed involving differential interactions of mutated and nonmutated RTs with its cellular partners involved in the regulation of ROS. This study establishes links between the expression of HIV-1 RT, production of ROS, induction of EMT, and enhanced propagation of RT-expressing tumor cells. Such scenario can be proposed as one of the mechanisms of HIV-induced/enhanced carcinogenesis not associated with immune suppression.Item The Immunogenicity in Mice of HCV Core Delivered as DNA Is Modulated by Its Capacity to Induce Oxidative Stress and Oxidative Stress Response(2019-02-28) Jansons, Juris; Sominskaya, Irina; Petrakova, Natalia; Starodubova, Elizaveta S.; Smirnova, Olga A.; Alekseeva, Ekaterina; Bruvere, Ruta; Eliseeva, Olesja; Skrastina, Dace; Kashuba, Elena; Mihailova, Marija; Kochetkov, Sergey N.; Ivanov, Alexander V.; Isaguliants, Maria G.; Department of PathologyHCV core is an attractive HCV vaccine target, however, clinical or preclinical trials of core-based vaccines showed little success. We aimed to delineate what restricts its immunogenicity and improve immunogenic performance in mice. We designed plasmids encoding full-length HCV 1b core and its variants truncated after amino acids (aa) 60, 98, 152, 173, or up to aa 36 using virus-derived or synthetic polynucleotides (core191/60/98/152/173/36_191v or core152s DNA, respectively). We assessed their level of expression, route of degradation, ability to trigger the production of reactive oxygen species/ROS, and to activate the components of the Nrf2/ARE antioxidant defense pathway heme oxygenase 1/HO-1 and NAD(P)H: quinone oxidoreductase/Nqo-1. All core variants with the intact N-terminus induced production of ROS, and up-regulated expression of HO-1 and Nqo-1. The capacity of core variants to induce ROS and up-regulate HO-1 and Nqo-1 expression predetermined their immunogenicity in DNA-immunized BALB/c and C57BL/6 mice. The most immunogenic was core 152s, expressed at a modest level and inducing moderate oxidative stress and oxidative stress response. Thus, immunogenicity of HCV core is shaped by its ability to induce ROS and oxidative stress response. These considerations are important in understanding the mechanisms of viral suppression of cellular immune response and in HCV vaccine design.Item Is There a Future for Traditional Immunogens When We Have mRNA?(2023-04) Kyuregyan, Karen K.; Jansons, Juris; Isaguliants, Maria; Research Department; Rīga Stradiņš UniversityItem Plasma and urinary extracellular vesicles as a source of RNA biomarkers for prostate cancer in liquid biopsies(2023-02-03) Bajo-Santos, Cristina; Brokāne, Agnese; Zayakin, Pawel; Endzeliņš, Edgars; Soboļevska, Kristīne; Belovs, Alberts; Jansons, Juris; Sperga, Māris; Llorente, Alicia; Radoviča-Spalviņa, Ilze; Lietuvietis, Vilnis; Linē, Aija; Rīga Stradiņš UniversityIntroduction: Extracellular vesicles (EVs) have emerged as a very attractive source of cancer- derived RNA biomarkers for the early detection, prognosis and monitoring of various cancers, including prostate cancer (PC). However, biofluids contain a mixture of EVs released from a variety of tissues and the fraction of total EVs that are derived from PC tissue is not known. Moreover, the optimal biofluid—plasma or urine—that is more suitable for the detection of EV- enclosed RNA biomarkers is not yet clear. Methodology: In the current study, we performed RNA sequencing analysis of plasma and urinary EVs collected before and after radical prostatectomy, and matched tumor and normal prostate tissues of 10 patients with prostate cancer. Results and Discussion: The most abundant RNA biotypes in EVs were miRNA, piRNA, tRNA, lncRNA, rRNA and mRNA. To identify putative cancer-derived RNA biomarkers, we searched for RNAs that were overexpressed in tumor as compared to normal tissues, present in the pre-operation EVs and decreased in the post-operation EVs in each RNA biotype. The levels of 63 mRNAs, 3 lncRNAs, 2 miRNAs and 1 piRNA were significantly increased in the tumors and decreased in the post-operation urinary EVs, thus suggesting that these RNAs mainly originate from PC tissue. No such RNA biomarkers were identified in plasma EVs. This suggests that the fraction of PC-derived EVs in urine is larger than in plasma and allows the detection and tracking of PC-derived RNAs.Item Reciprocal inhibition of immunogenic performance in mice of two potent dna immunogens targeting hcv-related liver cancer(2021-05) Jansons, Juris; Skrastina, Dace; Kurlanda, Alisa; Petkov, Stefan; Avdoshina, Darya; Kuzmenko, Yulia; Krotova, Olga; Trofimova, Olga; Gordeychuk, Ilya; Sominskaya, Irina; Isaguliants, Maria; Institute of Microbiology and VirologyChronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, and partially reverse liver disease, but they cannot cure HCV-related cancer. A possible remedy could be a multi-component immunotherapeutic vaccine targeting both HCV-infected and malignant cells, but also those not infected with HCV. To meet this need we developed a two-component DNA vaccine based on the highly conserved core protein of HCV to target HCV-infected cells, and a renowned tumor-associated antigen telomerase reverse transcriptase (TERT) based on the rat TERT, to target malignant cells. Their synthetic genes were expression-optimized, and HCV core was truncated after aa 152 (Core152opt) to delete the domain interfering with immunogenicity. Core152opt and TERT DNA were highly immunogenic in BALB/c mice, inducing IFN-γ/IL-2/TNF-α response of CD4+ and CD8+ T cells. Additionally, DNA-immunization with TERT enhanced cellular immune response against luciferase encoded by a co-delivered plasmid (Luc DNA). However, DNA-immunization with Core152opt and TERT mix resulted in abrogation of immune response against both components. A loss of bioluminescence signal after co-delivery of TERT and Luc DNA into mice indicated that TERT affects the in vivo expression of luciferase directed by the immediate early cytomegalovirus and interferon-β promoters. Panel of mutant TERT variants was created and tested for their expression effects. TERT with deleted N-terminal nucleoli localization signal and mutations abrogating telomerase activity still suppressed the IFN-β driven Luc expression, while the inactivated reverse transcriptase domain of TERT and its analogue, enzymatically active HIV-1 reverse transcriptase, exerted only weak suppressive effects, implying that suppression relied on the presence of the full-length/nearly full-length TERT, but not its enzymatic activity. The effect(s) could be due to interference of the ectopically expressed xenogeneic rat TERT with biogenesis of mRNA, ribosomes and protein translation in murine cells, affecting the expression of immunogens. HCV core can aggravate this effect, leading to early apoptosis of co-expressing cells, preventing the induction of immune response.Item Styrylpyridinium Derivatives for Fluorescent Cell Imaging(2023-09) Putralis, Reinis; Korotkaja, Ksenija; Kaukulis, Martins; Rudevica, Zhanna; Jansons, Juris; Nilova, Olga; Rucins, Martins; Krasnova, Laura; Domracheva, Ilona; Plotniece, Mara; Pajuste, Karlis; Sobolev, Arkadij; Rumnieks, Felikss; Bekere, Laura; Zajakina, Anna; Plotniece, Aiva; Duburs, Gunars; Department of Pharmaceutical ChemistryA set of styrylpyridinium (SP) compounds was synthesised in order to study their spectroscopic and cell labelling properties. The compounds comprised different electron donating parts (julolidine, p-dimethylaminophenyl, p-methoxyphenyl, 3,4,5-trimethoxyphenyl), conjugated linkers (vinyl, divinyl), and an electron-withdrawing N-alkylpyridinium part. Geminal or bis-compounds incorporating two styrylpyridinium (bis-SP) moieties at the 1,3-trimethylene unit were synthesised. Compounds comprising a divinyl linker and powerful electron-donating julolidine donor parts possessed intensive fluorescence in the near-infrared region (maximum at ~760 nm). The compounds had rather high cytotoxicity towards the cancerous cell lines HT-1080 and MH-22A; at the same time, basal cytotoxicity towards the NIH3T3 fibroblast cell line ranged from toxic to harmful. SP compound 6e had IC50 values of 1.0 ± 0.03 µg/mL to the cell line HT-1080 and 0.4 µg/mL to MH-22A; however, the basal toxicity LD50 was 477 mg/kg (harmful). The compounds showed large Stokes’ shifts, including 195 nm for 6a,b, 240 nm for 6e, and 325 and 352 nm for 6d and 6c, respectively. The highest photoluminescence quantum yield (PLQY) values were observed for 6a,b, which were 15.1 and 12.2%, respectively. The PLQY values for the SP derivatives 6d,e (those with a julolidinyl moiety) were 0.5 and 0.7%, respectively. Cell staining with compound 6e revealed a strong fluorescent signal localised in the cell cytoplasm, whereas the cell nuclei were not stained. SP compound 6e possessed self-assembling properties and formed liposomes with an average diameter of 118 nm. The obtained novel data on near-infrared fluorescent probes could be useful for the development of biocompatible dyes for biomedical applications.Item Validation of potential RNA biomarkers for prostate cancer diagnosis and monitoring in plasma and urinary extracellular vesicles(2023-11-30) Brokāne, Agnese; Bajo-Santos, Cristina; Zayakin, Pawel; Belovs, Alberts; Jansons, Juris; Lietuvietis, Vilnis; Martens-Uzunova, Elena S.; Jenster, Guido W.; Linē, Aija; Rīga Stradiņš UniversityIntroduction: Prostate cancer (PCa), one of the most prevalent malignancies affecting men worldwide, presents significant challenges in terms of early detection, risk stratification, and active surveillance. In recent years, liquid biopsies have emerged as a promising non-invasive approach to complement or even replace traditional tissue biopsies. Extracellular vesicles (EVs), nanosized membranous structures released by various cells into body fluids, have gained substantial attention as a source of cancer biomarkers due to their ability to encapsulate and transport a wide range of biological molecules, including RNA. In this study, we aimed to validate 15 potential RNA biomarkers, identified in a previous EV RNA sequencing study, using droplet digital PCR. Methods: The candidate biomarkers were tested in plasma and urinary EVs collected before and after radical prostatectomy from 30 PCa patients and their diagnostic potential was evaluated in a test cohort consisting of 20 benign prostate hyperplasia (BPH) and 20 PCa patients’ plasma and urinary EVs. Next, the results were validated in an independent cohort of plasma EVs from 31 PCa and 31 BPH patients. Results: We found that the levels of NKX3-1 (p = 0.0008) in plasma EVs, and tRF-Phe-GAA-3b (p < 0.0001) tRF-Lys-CTT-5c (p < 0.0327), piR-28004 (p = 0.0081) and miR-375-3p (p < 0.0001) in urinary EVs significantly decreased after radical prostatectomy suggesting that the main tissue source of these RNAs is prostate and/or PCa. Two mRNA biomarkers—GLO1 and NKX3-1 showed promising diagnostic potential in distinguishing between PCa and BPH with AUC of 0.68 and 0.82, respectively, in the test cohort and AUC of 0.73 and 0.65, respectively, in the validation cohort, when tested in plasma EVs. Combining these markers in a biomarker model yielded AUC of 0.85 and 0.71 in the test and validation cohorts, respectively. Although the PSA levels in the blood could not distinguish PCa from BPH in our cohort, adding PSA to the mRNA biomarker model increased AUC from 0.71 to 0.76. Conclusion: This study identified two novel EV-enclosed RNA biomarkers–NKX3-1 and GLO1–for the detection of PCa, and highlights the complementary nature of GLO1, NKX3-1 and PSA as combined biomarkers in liquid biopsies of PCa.Item Vēsturisks spriedums Latvijā: personas garantētā minimālā ienākumu līmeņa atbilstība Latvijas Republikas Satversmei(Rīgas Stradiņa universitāte / Rīga Stradiņš University, 2020) Jansons, Juris; Latvijas Republikas TiesībsargsRakstā ir analizēts Latvijas Republikas Satversmes tiesas spriedums lietā Nr. 2019-24-03, kuras izskatīšanā šī raksta autors piedalījās kā pieteicējs. Ar apstrīdēto normu noteiktais garantētais minimālais ienākumu līmenis ir zemākais tiesību aktos noteiktais ienākumu vai resursu līmenis, kas ļauj personai, kura atzīta par trūcīgu, pretendēt uz noteikta veida sociālo palīdzību. No 2020. gada 1. janvāra garantētais minimālais ienākumu līmenis personai bija noteikts 64 eiro mēnesī. 2020. gada 25. jūnijā Latvijas Republikas Satversmes tiesa pasludināja spriedumu, ar kuru atzina Ministru kabineta 2012. gada 18. decembra noteikumu Nr. 913 “Noteikumi par garantēto minimālo ienākumu līmeni” 2. punktu par neatbilstošu Latvijas Republikas Satversmes 1. un 109. pantam un spēkā neesošu no 2021. gada 1. janvāra. Ar minēto spriedumu sociālo un ekonomisko tiesību jomā Latvijā ir noticis būtisks pavērsiens. Šis ir vēsturisks spriedums, kas kalpo kā vadlīnija sociālās drošības sistēmas sakārtošanai Latvijā ne vien attiecībā uz garantēto minimālo ienākumu līmeni, bet arī uz visu sociālo palīdzību un pakalpojumiem kopumā. Īpaši jāuzsver, ka pamattiesību tvērumā Satversmes tiesa konkrēto sociālās drošības elementu aplūkoja caur cilvēka cieņas prizmu, un jādomā, ka tas būtiski ietekmēs vismazāk aizsargāto Latvijas iedzīvotāju labklājību. Rakstā tika izmantotas vispārzinātniskās pētījumu metodes un tiesību normu interpretācijas metodes. Vienlaikus tika analizēti starptautiskie un Latvijas Republikas normatīvie akti, Latvijas Republikas tiesu prakses piemēri, kā arī veikta zinātniskās literatūras izpēte.