The clinical success of calcium phosphate bone grafts (CPs) largely depends on the body’s immune response. However, traditional biocompatibility tests use healthy organisms and cannot predict effectiveness in patients with common chronic inflammatory diseases. This study examines how inflammation modulates the immune response, in vitro and in vivo, to low-temperature biomimetic CPs: dicalcium phosphate dihydrate (DCPD), octacalcium phosphate (OCP), and hydroxyapatite (HAp). In vitro studies involved human monocytes, macrophages, lymphocytes, and mesenchymal stromal cells (MSCs), with or without pro-inflammatory activation. In vivo biocompatibility was assessed via subcutaneous implantation in rats, with or without Complete Freund’s Adjuvant (CFA)-induced inflammation. Under normal conditions, all CP caused minimal immune reactivity. Inflammation-activated macrophages, however, triggered an acute reaction with significantly increased TNF-α and IL-1β secretion. Healthy and inflamed animals showed sharp contrasts. Although all materials exhibited thickened fibrous capsules during inflammation, biocompatibility varied markedly: DCPD performed best by promoting angiogenesis with minimal inflammation; HAp provoked the most severes response, including tissue necrosis and signs of rejection; OCP showed intermediate effects, with angiogenesis but notable fibrosis. Inflammatory processes critically influence CP biocompatibility; materials biocompatible in healthy organisms can induce fibrosis or rejection under inflammation. Disease-relevant, immune-challenged models are essential to predict clinical efficacy and safety.

Hypaphorines, tryptophan derivatives, have anti-inflammatory activity, but their mechanism of action was largely unknown. Marine alkaloid L-6-bromohypaphorine with EC₅₀ of 80 μM acts as an agonist of α7 nicotinic acetylcholine receptor (nAChR) involved in anti-inflammatory regulation. We designed the 6-substituted hypaphorine analogs with increased potency using virtual screening of their binding to the α7 nAChR molecular model. Fourteen designed analogs were synthesized and tested in vitro by calcium fluorescence assay on the α7 nAChR expressed in neuro 2a cells, methoxy ester of D-6-iodohypaphorine (6ID) showing the highest potency (EC₅₀ 610 nM), being almost inactive toward α9α10 nAChR. The macrophages cytometry revealed an anti-inflammatory activity, decreasing the expression of TLR4 and increasing CD86, similarly to the action of PNU282987, a selective α7 nAChR agonist. 6ID administration in doses 0.1 and 0.5 mg/kg decreased carrageenan-induced allodynia and hyperalgesia in rodents, in accord with its anti-inflammatory action. Methoxy ester of D-6-nitrohypaphorine demonstrated anti-oedemic and analgesic effects in arthritis rat model at i.p. doses 0.05–0.26 mg/kg. Tested compounds showed excellent tolerability with no acute in vivo toxicity in dosages up to 100 mg/kg i.p. Thus, combining molecular modelling and natural product-inspired drug design improved the desired activity of the chosen nAChR ligand.

Poloxamer 188 is a polymer that is used as a carrier and stabilizer of pharmacological agents. It has been demonstrated to enhance red blood cell and hemoglobin levels in healthy animals and in select clinical cases. The objective of this study was to assess the efficacy of Poloxamer 188 in CBA mice when administered repeatedly in the carboplatin-induced myelosuppression model. The mice were administered carboplatin once at a dose of 100 mg/kg, and then Poloxamer 188 was orally administered daily at doses of 10 mg/kg, 100 mg/kg, 500 mg/kg, and 1000 mg/kg for 7 and 21 days. Poloxamer 188 at a dose of 1000 mg/kg was found to bring the level of 2,3-bisphosphoglycerate in red blood cells close to control level (p = 0.1331 for the control group compared to Poloxamer at a dose 1000 mg/kg) already from day 8 of the study and in bone marrow resulted in regulation of genes responsible for hematopoiesis. G-GSF at day 8 and TNFα at day 22 gene expression was significantly decreased by 54% (p = 0.012) and 16% (p = 0.024), respectively, with Poloxamer 188 administration at a dose of 100 mg/kg. Additionally, in the bone marrow, the treatment was seen to exert a positive regulatory effect on the genes responsible for hematopoiesis. These findings are consistent with the observed increase in red blood cell by 6.7% (p = 0.001), hemoglobin by 4.7% (p = 0.0053), and reticulocyte percentage by 53.6% (p < 0.0001) following Poloxamer 188 administration at a dose of 1000 mg/kg in CBA mice with myelosuppression.

Ischemic stroke remains one of the main causes of disability, which requires the search for improved methods of its prevention. In this study, the effectiveness of a hyperoxic oxygen–helium mixture in preventing brain damage during ischemia in Sprague Dawley rats was studied. The blood gas composition, the concentration of 2,3-diphosphoglycerate in erythrocytes, and functional indices were assessed. The results showed that oxygen–helium mixtures exhibit a pronounced protective effect in ischemic stroke, improving tissue oxygenation and reducing neurological deficit.

Background/Objectives: Hemorrhagic shock (HS) is one of the leading causes of disability and mortality in intensive care units. Animal modeling of HS is important for preclinical research to elucidate mechanisms and develop treatments. Methods: Adult male SD rats were divided into three groups, half of which were euthanized on day 8 and the other half on day 29 after HS. HS was simulated in awake animals by withdrawing blood from the carotid artery at a volume of 40% of circulating blood volume (CBV). One hour after HS, volume resuscitation therapy (VRT) was made by administering albumin-containing saline (AS) or autologous blood (AB) at 20% of CBV. Arterial pressure (AP), heart rate (HR), body temperature, blood gases, and blood metabolites, body weight gain, hemostasis, and blood cellular composition were analyzed. On days 8 and 29, bone marrow composition, organ weight, and histology were analyzed. Results: During blood withdrawal, AP dropped, HR increased, and hypothermia developed. After HS and subsequent VRT, 30% of animals receiving SA died, while all animals receiving AB survived. Following HS, a negative weight gain trend, anemia, pronounced inflammatory reaction, and coagulopathy developed. After HS, animals experienced an increase in partial oxygen pressure, a decrease in partial carbon dioxide pressure, total arterial oxygen content in arterial blood, stress-induced glycemia, and metabolic lactatemia. In bone marrow, the number of erythroid cells increased, while leukocyte and lymphocyte numbers decreased. HS resulted in increased spleen weight with increased extramedullary hematopoiesis. Ischemic kidney tissue damage with a decrease in kidney weight was observed, as well as post-ischemic accidental thymus involution with a catastrophic decrease in its weight. In addition, ischemic brain damage was observed in some animals. Animals showed a compensatory increase in hematopoiesis. All changes were less pronounced in AB-treated animals. Conclusions: We have developed a suitable model of HS, comparable to a similar condition in humans. This model can be easily reproduced and applied in most laboratories conducting preclinical studies.

Arterial gas embolism can result from complications related to medical and surgical procedures, as well as a direct entry of air into the systemic circulation due to the disruption of the alveolar-capillary barrier. Since air in the arterial circulation can lead to organ ischemia, this life-threatening pathology requires prompt intervention. In this study, we demonstrated the effectiveness of using a hyperoxic heated helium-oxygen mixture in cerebral arterial air embolism. Oxygen therapy under normobaric conditions did not affect the outcome of arterial air embolism. A continuous inhalation session for 30 min, or intermittent inhalation sessions 3 times for 5 min each, eliminated foci of ischemic stroke in rats.