{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T08:45:36Z","timestamp":1785746736673,"version":"3.56.0"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cyclophosphamide is widely used in oncology, autoimmune disorders, and transplantation-related conditioning or post-transplant immunosuppression. However, its therapeutic value is limited by hematopoietic and lymphoid toxicity, including leukopenia, neutropenia, anemia, thrombocytopenia, bone marrow suppression, thymic injury, and prolonged impairment of T-cell recovery. These effects may occur after pulsed intravenous administration, high-dose regimens used in transplantation or severe refractory disease, and continuous low-dose\/metronomic exposure. Therefore, there is a medical need for pharmacological agents capable of compensating cyclophosphamide-induced hematopoietic and lymphopoietic suppression without causing uncontrolled stimulation of early progenitor cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To evaluate the hematopoietic and T-lymphopoiesis-stimulating activity of BIV under cyclophosphamide-induced hematopoietic and T-lymphopoietic suppression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Cyclophosphamide-induced hematopoietic- and T-lymphopoiesis-suppressive models were established on laboratory albinos rats and C57BL6\/J mice. Peripheral blood hematological indices in rats were measured using hematology analyzers. Hematopoietic stem cells, thymocyte subsets, Th\n                      <jats:sub>act<\/jats:sub>\n                      , T\n                      <jats:sub>reg<\/jats:sub>\n                      , T\n                      <jats:sub>mem<\/jats:sub>\n                      , CTL cell populations, and erythroid cells from the bone marrow, thymus, and spleen were analyzed by flow cytometry. Statistical analysis was performed using one-way ANOVA (p &amp;lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In rats with CPh-induced hematopoietic suppression, BIV supported partial recovery of erythrocyte and hemoglobin parameters and improved leukopoietic indices under CPh-induced hematopoietic suppression. The \u03b2-cyclodextrin complex of 5-benzyl-7-(o-fluorobenzylidene)-2,3-bis(o-fluorophenyl)-3,3a,4,5,6, 7-hexahydro-2H-pyrazolo[4,3-c]pyridine (BIV) demonstrated a consistent moderate activity in restoring the overall level of CD3\u03b5+CD19\u2212 T lymphocytes in the bone marrow and thymus. In the bone marrow, BIV uniformly increased the reduced levels of CD3\u03b5+CD19\u2212 T lymphocytes and CD3\u03b5+CD44\n                      <jats:sup>+<\/jats:sup>\n                      T\n                      <jats:sub>mem<\/jats:sub>\n                      memory T cells to physiological normal values. In the spleen, BIV restored the decreased levels of CD25+FoxP3+ T\n                      <jats:sub>reg<\/jats:sub>\n                      regulatory lymphocytes and CD28\n                      <jats:sup>+<\/jats:sup>\n                      CD44\n                      <jats:sup>+<\/jats:sup>\n                      T\n                      <jats:sub>mem<\/jats:sub>\n                      memory T cells to physiological normal levels, while reducing the elevated levels of CD3\u03b5+CD8a+ CTL cytotoxic T lymphocytes and CD4\n                      <jats:sup>+<\/jats:sup>\n                      CD25\n                      <jats:sup>+<\/jats:sup>\n                      Th\n                      <jats:sub>act<\/jats:sub>\n                      activated helper T cells to values corresponding to the physiological norm.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BIV demonstrated notable hematopoietic- and T-lymphopoiesis-modulating activity. The compound partially restored erythropoiesis as well as central and peripheral T-lymphopoiesis, while providing balanced regulation of cytotoxic, regulatory, and memory T-cell subsets in cyclophosphamide-induced T-lymphopoiesis-suppressive models. Several evaluated T-lymphocyte subpopulations approached or returned to physiological control levels under the experimental conditions, although full translational validation requires further pharmacological and toxicological investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1852779","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T07:59:19Z","timestamp":1785743959000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hematopoietic and T-lymphopoiesis-stimulating effects of a fluorinated pyrazolopiperidine \u03b2-cyclodextrin complex in cyclophosphamide-induced hematopoietic suppression"],"prefix":"10.3389","volume":"17","author":[{"given":"Assel","family":"Ten","sequence":"first","affiliation":[{"name":"Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A. B. 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