Balnytė, Ingrida

Nors širdies autonominė inervacija plačiai tiriama, vidusieninių aferentinių struktūrų sandara, pasiskirstymas ir reikšmė širdies nervinei reguliacijai nėra pakankamai išaiškinti. Šio darbo tikslas – nustatyti širdies vidusieninių aferentinių struktūrų anatomiją ir apibūdinti jų pasiskirstymą, morfologiją, cheminį fenotipą bei galimus ryšius su vidusieniniais neuronais ir mažomis intensyviai fluorescuojančiomis (MIF) ląstelėmis. Tyrimo metu žmogaus ir skirtingų rūšių gyvūnų širdyse buvo tiriamos juntamosios nervinės galūnės, nustatomi jų morfologiniai ir cheminiai tipai, atliekama jų pasiskirstymo bei tarprūšinė analizė. Taip pat įvertinti nervinių galūnių ryšiai su širdies vidusieniniais nerviniais mazgais ir MIF ląstelėmis. Gauti rezultatai parodė, kad širdyje egzistuoja du pagrindiniai juntamųjų nervinių galūnių tipai – puokščių ir krepšelio tipo nervinės galūnės. Nustatyti jų anatominiai ypatumai praplečia širdies refleksogeninių zonų sampratą ir leidžia geriau suprasti aferentinių signalų integraciją širdies vidusieninėje nervinėje sistemoje. Pirmą kartą aprašyta žiurkių širdies MIF ląstelių inervacija ir jų galimi ryšiai su simpatinėmis, parasimpatinėmis bei juntamosiomis nervinėmis skaidulomis. Šie duomenys suteikia naujų žinių apie širdies nervinės reguliacijos mechanizmus ir gali būti reikšmingi tiriant aritmijų, širdies nepakankamumo bei kitų širdies ligų patogenezę.

Obesity profoundly impairs musculotendinous structure and function, but the extent to which these alterations can be reversed remains unclear. This study compared the effects of aerobic exercise (EX) and caloric restriction (CR) on the recovery of muscle-tendon structural integrity, contractile performance and passive mechanical properties in high-fat diet-induced obese mice. Male C57BL/6J mice were fed a high-fat diet for 28 weeks and remained on this diet during a subsequent 6 week intervention of either treadmill training (OBEX, 5 days week-1 at at 45-65% ˙VO2max ) or 30% caloric restriction (OBCR), whereas controls received standard chow with (CNEX) or without exercise (CN). Muscle [soleus, extensor digitorum longus (EDL)] and Achilles tendon mechanical properties, morphology and composition were assessed alongside circulating and tissue-specific remodelling markers. OB had higher circulating transforming growth factor beta 1, periostin and advanced glycation end products, accompanied by higher muscle and tendon fibrosis. These molecular and structural alterations coincided with slower contraction-relaxation kinetics, lower specific force and increased tissue viscosity. EX but not CR increased tissue energy storage capacity. OBCR but not OBEX had lower muscle AGEs and muscle collagen fraction than OB. In CR, this was associated with significant improvements in muscle-specific force. However, tendon properties remained largely unaffected following CR. In summary, a 6 week CR decreased body mass, normalized glucose tolerance, reduced fibrosis and improved muscle contractility. By contrast, EX enhanced aerobic capacity and modestly improved tissue mechanical behaviour, but had limited effects on body mass, fibrosis, and muscle contractile function. These findings indicate that caloric restriction and exercise induce distinct, only partially overlapping adaptations, highlighting differential contributions of metabolic and mechanical pathways to the recovery of muscle-tendon function in obesity. KEY POINTS: Obesity is known to induce skeletal muscle dysfunction, but it is unclear to what extent this can be reversed by lifestyle interventions such as exercise or reduced food intake. Using a mouse model of diet induced obesity, we compared aerobic exercise with caloric restriction to assess recovery of muscle-tendon structure and function. Obesity caused excess connective tissue to accumulate in muscles and tendons, leading to lower specific force, slower contraction and relaxation, and a stiffer and more viscous muscle-tendon complex. Compared to exercise, caloric restriction more effectively restored muscle specific force and tissue composition than exercise, whereas tendon recovery remained limited. Caloric restriction and exercise elicit distinct, partly overlapping adaptations, suggesting that metabolic and mechanical pathways differentially drive muscle-tendon recovery following diet-induced obesity.

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) develops through inflammation-driven preneoplastic alterations characterized by epidermal hyperplasia, dysplasia, and increased proliferative activity. C-phycocyanin (C-PC) possesses antioxidant and anti-inflammatory properties; however, its topical potential to attenuate a tumour-promoting cutaneous microenvironment is limited by poor skin penetration. This study evaluated the effects of C-PC-loaded transfersomes in a 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse model of skin carcinogenesis. Methods: Male BALB/c mice were assigned to six groups (n = 10 per group). Carcinogenesis was initiated with a single topical application of DMBA, followed by twice-weekly TPA application for 16 weeks. C-PC-loaded transfersomes (1 mg/mL or 10 mg/mL) were applied topically. Histopathological assessment included epidermal thickness, rete ridge depth, mitotic activity, mast cell density, and semi-quantitative scoring of hyperplasia, dysplasia, and inflammation. Ki-67 immunohistochemistry was used to evaluate basal and suprabasal proliferation. Results: Carcinogen exposure induced marked epidermal thickening, severe dysplasia, increased mitotic activity, elevated Ki-67 expression, and pronounced dermal inflammation. Treatment with C-PC-loaded transfersomes significantly reduced epidermal thickness, rete ridge depth, mast cell density, mitotic counts, and suprabasal Ki-67 index. The 1 mg/mL concentration demonstrated the most consistent attenuation of dysplasia severity and inflammatory changes. No adverse histopathological alterations were observed in internal organs. Conclusions: These findings indicate that transfersome-mediated topical delivery of C-PC attenuates early inflammation-driven epidermal remodelling and tumour-promoting alterations in experimental skin carcinogenesis, supporting its potential as a topical preventive strategy.

Background: Early tumor-promoting events in skin carcinogenesis are characterized by increased keratinocyte proliferation, epidermal hyperplasia, and architectural alterations of the skin. Natural bioactive compounds with antiproliferative properties may represent promising chemopreventive strategies. C-phycocyanin (C-PC), a cyanobacteria - derived biliprotein, has demonstrated cytostatic and anti-inflammatory effects in experimental models (1-2). However, its topical delivery and influence on early tumor promotion require further investigation. Aim(s): To evaluate whether C-PC-loaded transfersomes modulate early proliferation- and dysplasiaassociated alterations in a mouse DMBA/TPA model of skin tumor promotion. Methods: Experimental skin carcinogenesis was induced using a classical DMBA/TPA initiation– promotion protocol. Animals were treated with C-PC-loaded transfersomes, empty transfersomes, or cancerogenic formulations. Histological assessment included epidermal thickness, rete ridge depth, and dysplasia grading. Immunohistochemical analysis of Ki-67 expression was performed separately in basal and suprabasal epidermal layers. Correlation analysis between suprabasal Ki-67 index and histopathological parameters was conducted. Statistical analysis included Welch’s ANOVA with Games–Howell post hoc test, Kruskal–Wallis analysis, and Spearman correlation (p < 0.05). Results: Tumor promotion induced marked epidermal hyperplasia, increased rete ridge formation, and elevated Ki-67 expression extending into suprabasal layers. Treatment with C-PC-loaded transfersomes significantly reduced epidermal thickness and suprabasal proliferative activity compared to untreated promoted skin. Suprabasal Ki-67 index positively correlated with epidermal thickness, rete ridge depth, and dysplasia grade, indicating its sensitivity as a marker of early pathological proliferation. Conclusion: Topical delivery of C-PC via transfersomes was associated with attenuation of early proliferative and structural alterations during skin tumor promotion in this experimental model. Further studies are required to clarify the underlying mechanisms and to determine their potential relevance in long-term chemopreventive strategies.

Background Angiogenesis plays a critical role in tumor development, with neuropilin receptors (NRPs) involved in this process through their interactions with vascular endothelial growth factor (VEGF) and semaphorins. SEMA3A, a member of class 3 semaphorins, demonstrates strong antiangiogenic potential. In this study, the C-terminal basic domain of SEMA3A was replaced with the heparin-binding domain (HBD) of VEGF165, hypothesizing that the resultant chimeric protein SEMA-PSI-IG-HBD would enhance antiangiogenic efficacy by: (1) competing with VEGF for NRPs (2) utilizing the HBD as a molecular anchor to increase the residence time and local concentration of the hybrid within the tumor microenvironment.

Obesity is associated with chronic inflammation, metabolic dysregulation, and significant remodeling of particularly muscle and tendon. Emerging evidence implicates periostin (POSTN), a non-structural matricellular protein, as a key mediator of extracellular matrix (ECM) remodeling in response to metabolic and mechanical stressors. POSTN's modular structure enables it to orchestrate ECM architecture by binding collagen, fibronectin, and matrix-modifying enzymes, positioning it as a central modulator of mechanochemical tissue properties. Normally POSTN is expressed at a low level but becomes upregulated during injury and inflammation that are associated with fibrotic responses. In obesity POSTN expression is elevated systemically and locally in adipose, muscle, and tendon tissues, where it may contribute to the maladaptive remodeling through integrin-mediated activation of signaling pathways such as PI3K/Akt and TGF-β/Smad. This promotes collagen deposition, matrix cross-linking, and fibrosis, impairing tissue function and regenerative capacity. Evidence from obesity and muscle injury models suggests that POSTN may act as both a biomarker of, and a therapeutic target for mitigating, fibrotic changes in musculoskeletal tissues. This review highlights POSTN's context-dependent roles and its potential as a mechanistic link between metabolic dysfunction and musculotendinous tissue degeneration in obesity.

Background/Objectives: The ineffectiveness of current treatments for glioblastoma underscores the urgent need for effective alternatives. This study aimed to investigate the effectiveness of sodium dichloroacetate (NaDCA) and a sodium valproate NaDCA combination (NaVPA–NaDCA) on formed patients’ primary cell tumors on the chick embryo chorioallantoic membrane (CAM). Methods: Glioblastoma tissue samples were obtained from three patients during tumor surgery. WHO grade IV, IDH wild-type, and a strong positive cytoplasmic GFAP reaction in tumor cells characterized the investigated glioblastoma cases. The tumor cells GBM2-2F, GBM2-3F, and GBM-4M from the patients were examined. Histological examination of tumor invasion into CAM, angiogenesis, and immunohistochemical expression of GFAP-, PCNA-, p53-, EZH2- and vimentin-positive cells were examined. Results: No difference in GFAP expression was observed between the patient’s GBM tumor tissue and the tumor formed on CAM from the same patient’s tumor cells. There were no significant differences in invasion or in the frequency of GFAP- and p53-positive cells among the study control groups. The expression of PCNA-, EZH2-, and vimentin-positive cells in control tumors varied significantly. Treatment significantly reduced the incidence of tumor invasion in GBM2-2F and GBM2-4M and did not affect GBM2-3F tumors; treatment also significantly reduced GFAP expression in GBM2-3F and GBM2-4M and did not affect GBM2-2F tumors. The treatment with NaVPA–NaDCA significantly reduced the expression of PCNA, p53, EZH2 and vimentin in the tested tumors. Conclusions: Data demonstrated an antitumor effect of NaVPA–NaDCA in an in vivo model of a patient’s primary glioblastoma cells.

Nepaisant reikšmingos kataraktos chirurgijos pažangos, pooperacinių komplikacijų išvengti nepavyksta. Viena sudėtingiausių – vėlyvoji intraokulinio lęšio (IOL) – kapsulės maišelio komplekso dislokacija, pasireiškianti praėjus daugeliui metų po sėkmingos kataraktos operacijos. Jos dažnis siekia 0,1–3 proc. ir toliau didėja dėl augančios pseudofakiją turinčių pacientų populiacijos bei ilgėjančios pseudofakijos trukmės. Todėl ši komplikacija tampa vis aktualesne oftalmologijos problema. Galimi du pagrindiniai gydymo būdai: pašalinti dislokuotą IOL ir pakeisti jį nauju arba fiksuoti esamą IOL prie akies audinių. Naujausi tyrimai rodo didėjantį susidomėjimą IOL fiksavimo metodų rezultatais ir pastangas išsaugoti esamą IOL, tačiau vis dar trūksta įrodymų, kaip skirtingi sprendimai veikia regą ir akies morfologiją. IOL fiksacija prie skleros yra daugiausiai ištirtas metodas, tačiau turi trūkumų, o apie alternatyvias technikas, tokias kaip IOL fiksacija prie rainelės, duomenų nepakanka. Šio tyrimo tikslas – įvertinti IOL–kapsulės maišelio komplekso dislokacijos sukeliamus regos bei akies morfologinius pakitimus, bei palyginti jų pokyčius po skirtingų IOL dislokacijos chirurginio gydymo metodų: po IOL fiksacijos prie rainelės ir po IOL pakeitimo į priekinės kameros IOL.

The search for an effective treatment for adult high-grade glioblastoma (GBM) remains urgent. Background/Objectives: The study aimed to determine the expression of carcinogenesis-related genes, such as SLC12A2, SLC12A5, CDH1, CDH2, EZH2, and GFAP, in primary glioblastoma (WHO Grade IV; IDH-wild-type) cells from three adult women: GBM5-1, GBM5-2F, and GBM5-3F. Methods: The impact of the combination of sodium valproate and sodium dichloroacetate (2 mM NaVPA–3 mM NaDCA) on the expression of these genes was determined and compared with the effects of 50 µM temozolomide after 24 h of treatment. Results: 2 mM NaVPA–3 mM NaDCA, as well as temozolomide, had individual impacts on the SLC12A2, SLC12A5, CDH1, CDH2, EZH2, and GFAP expressions of tested GBM5-1, GBM5-2F, and GBM5-3F primary cells of female GBM patients. Conclusions: The combination of 2 mM NaVPA–3 mM NaDCA may have an advantage in antitumor activity and may be more effective than TMZ; however, the effect is individual.

To date, there is no effective treatment for glioblastoma (GBM). This study aimed to compare the effectiveness of sodium dichloroacetate (NaDCA), a valproic acid and NaDCA combination (VPA–NaDCA), or temozolomide (TMZ) on U87 and T98G cell tumors on the chick embryo chorioallantoic membrane (CAM), and on the expression of proliferating cell nuclear antigen (PCNA), polycomb inhibitory complex catalytic subunit 2 (EZH2), and TP53 gene-encoded p53 protein (p53) in tumors on the CAM, and SLC12A2 (gene encoding Na+-K+-2Cl− (NKCC1) co-tarnsporter), SLC12A5 (gene encoding K+-Cl− (KCC2) co-transporter), SLC5A8 (gene encoding Na+-dependent monocarboxylate transporter) and CDH1 (gene encoding the E-cadherin protein) and CDH2 (gene encoding the N-cadherin protein) in cells. VPA–NaDCA and TMZ reduced the invasion of U87 and T98G tumors, as well as the expression of PCNA and EZH2 in the tumor. TMZ reduced p53 expression in tumors from both cell lines, whereas VPA–NaDCA did not affect the expression of this marker. VPA–NaDCA, but not TMZ, reduced SLC12A2 expression in T98G cells. However, VPA–NaDCA and TMZ did not affect SLC12A2 expression in U87 cells. VPA–NaDCA increased SLC5A8 expression only in U87 cells, and TMZ did not affect gene expression in either cell line. Only VPA–NaDCA increased CDH1 expression and decreased CDH2 expression in T98G cells, whereas TMZ had no effect on gene expression in the study cells. This study demonstrated that VPA–NaDCA exhibits a more effective anticancer effect than NaDCA. The data suggest that VPA–NaDCA has a more effective impact than TMZ; however, the effect of investigational medicines on carcinogenesis varies depending on the cell line. The study of the efficacy of drugs used to treat tumors on the CAM and cells demonstrates that it is essential to assess the effectiveness of treatment, which should be personalized, before administering chemotherapy.