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1.
Mol Cell Probes ; 76: 101969, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38964425

ABSTRACT

The progression and pathogenesis of membranous glomerulonephritis (MGN) are inextricably linked to chronic inflammation. Despite improving clinical remission rates due to the application of cyclophosphamide (CYC), treatment of MGN still requires further exploration. Ruxolitinib (Ruxo) negatively affects the signaling pathways participating in the production of pro-inflammatory cytokines. Hence, we investigated whether the combination of CYC and Ruxo can modulate inflammation through influencing T helper 17 (Th17) lineages and regulatory T cells (Tregs). Passive Heymann nephritis (PHN), an experimental model of MGN, was induced in a population of rats. Then, the animals were divided into five groups: PHN, CYC-receiving, Ruxo-receiving, CYC-Ruxo-receiving PHN rats, and healthy controls. After 28 days of treatment, biochemistry analysis was performed and splenocytes were isolated for flowcytometry investigation of Th17 cells and Tregs. The correlative transcription factors of the cells, alongside their downstream cytokine gene expressions, were also assessed using real-time PCR. Furthermore, serum cytokine signatures for the lymphocytes were determined through ELISA. The combination of CYC and Ruxo significantly reduced the serum values of urea in rats versus the PHN group (24.62 ± 7.970 vs. 40.60 ± 10.81 mg/dL). In contrast to Treg's activities, the functionality of Th17 cells noticeably increased not only in PHN rats but also in CYC or Ruxo-receiving PHN animals when compared with the control (10.60 ± 2.236, 8.800 ± 1.465, 8.680 ± 1.314 vs. 4.420 ± 1.551 %). However, in comparison to the PHN group, the incidence of Th17 cells notably fell in rats receiving CYC and Ruxo (10.60 ± 2.236 vs. 6.000 ± 1.373 %) in favor of the Treg's percentage (5.020 ± 1.761 vs. 8.980 ± 1.178 %), which was verified by the gene expressions and cytokine productions correlative to these lymphocytes. The combination of CYC and Ruxo was able to decline Th17 cells in favor of Tregs improvement in PHN rats, suggesting an innovative combination therapy in MGN treatment approaches.

2.
Growth Factors ; 41(3): 165-177, 2023 08.
Article in English | MEDLINE | ID: mdl-37351894

ABSTRACT

Autologous platelet-rich plasma (PRP) and platelet lysate (PL) are nowadays promising candidates in the treatment of articular cartilage lesions. We aimed to compare PRP and PL injection effectiveness in patients with knee osteoarthritis (KOA). A total of fifty women with KOA were included in the study. Patients were treated with intra-articular injections of PRP and PL. Clinical outcomes were evaluated using the comparison of VAS, WOMAC, and ROM scores. The concentration levels of growth factors and cytokines were measured by ELISA. All patients showed significant improvements in pain and function following treatment of KOA with PL and PRP compared to baseline. Moreover, PL's concentration of growth factors was significantly higher than PRP. A significant increase was also observed in all of the aforementioned mediators in both PRP and PL products compared to control. These results can introduce PL as a promising and alternative option for KOA therapy in the future.


Subject(s)
Osteoarthritis, Knee , Platelet-Rich Plasma , Humans , Female , Osteoarthritis, Knee/drug therapy , Hyaluronic Acid , Treatment Outcome , Injections, Intra-Articular
3.
Immunol Lett ; 248: 1-6, 2022 08.
Article in English | MEDLINE | ID: mdl-35679971

ABSTRACT

Several parts are possessed by kidneys in fundamental physiological functions, which include the regulation of blood pressure, production of blood cells, homeostasis of water, salt, and calcium, and the balance of acids and bases. Thus, several pathologies could cause, or be caused by, renal dysfunction. Chronic kidney failure, or chronic kidney disease, is described as the time when kidneys lose their function gradually. Excess fluids and wastes are filtered from the blood and excreted to urine by kidneys. However, in case of advanced stages of chronic kidney failures, deleterious levels of wastes, electrolytes, and fluids could be observed in the body. The activation of immune system, as well as inflammation, are factors with paramount significance in the development of chronic and acute renal failure. Two main branches, including innate and adaptive immunity, compose the immune system. As the first responder, the innate immunity responds nonspecifically to invading pathogens. However, the adaptive immunity provides efficient recognition and response to particular pathogens, and enjoys a memory which is useful in second exposure to a pathogen. Different functions, the mediation of which takes place through cytokines, immune cell subsets, and protein cascades, are performed by these two immune responses. This review is aimed at focusing on data which have linked adaptive immunity, particularly T-cells and inflammatory mechanisms, to the development of renal failure.


Subject(s)
Acute Kidney Injury , Adaptive Immunity , Acute Kidney Injury/etiology , Humans , Immunity, Innate , Inflammation/pathology , Kidney , T-Lymphocytes
4.
Life Sci ; 277: 119463, 2021 Jul 15.
Article in English | MEDLINE | ID: mdl-33862110

ABSTRACT

Through the regulation of gene expression, microRNAs (miRNAs) are capable of modulating vital biological processes, such as proliferation, differentiation, and apoptosis. Several mechanisms control the function of miRNAs, including translational inhibition and targeted miRNA degradation. Through utilizing high-throughput screening methods, such as small RNA sequencing and microarray, alterations in miRNA expression of kidneys have recently been observed both in rodent models and humans throughout the development of chronic kidney disease (CKD) and acute kidney injury (AKI). The levels of miRNAs in urine supernatant, sediment, and exosomal fraction could predict novel biomarker candidates in different diseases of kidneys, including IgA nephropathy, lupus nephritis, and diabetic nephropathy. The therapeutic potential of administrating anti-miRNAs and miRNAs has also been reported recently. The present study is aimed at reviewing the state-of-the-art research with regards to miRNAs involved in renal disorders related to primary podocyte dysfunction by laying particular emphasis on Focal Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD) and Membranous Nephropathy (MN).


Subject(s)
Kidney Diseases/genetics , MicroRNAs/genetics , Podocytes/metabolism , Apoptosis/genetics , Biomarkers/metabolism , Diabetic Nephropathies/metabolism , Glomerulonephritis, Membranous/metabolism , Glomerulosclerosis, Focal Segmental/metabolism , Humans , Kidney/metabolism , Kidney/pathology , Kidney Diseases/metabolism , Lupus Nephritis/metabolism , MicroRNAs/metabolism , Nephrosis, Lipoid/metabolism , Podocytes/physiology , Renal Insufficiency, Chronic/genetics , Renal Insufficiency, Chronic/metabolism
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