Calycosin alleviates titanium particle-induced osteolysis by modulating macrophage polarization and subsequent osteogenic differentiation.

Periprosthetic osteolysis (PPO) caused by wear particles is one of the leading causes of implant failure after arthroplasty. Macrophage polarization imbalance and subsequent osteogenic inhibition play a crucial role in PPO. Calycosin (CA) is a compound with anti-inflammatory and osteoprotective properties. This study aimed to evaluate the effects of CA on titanium (Ti) particle-induced osteolysis, Ti particle-induced macrophage polarization and subsequent osteogenic deficits, and explore the associated signalling pathways in a Ti particle-stimulated calvarial osteolysis mouse model using micro-CT, ELISA, qRT-PCR, immunofluorescence and western blot techniques. The results showed that CA alleviated inflammation, osteogenic inhibition and osteolysis in the Ti particle-induced calvarial osteolysis mouse model in vivo. In vitro experiments showed that CA suppressed Ti-induced M1 macrophage polarization, promoted M2 macrophage polarization and ultimately enhanced osteogenic differentiation of MC3T3-E1 cells. In addition, CA alleviated osteogenic deficits by regulating macrophage polarization homeostasis via the NF-κB signalling pathway both in vivo and in vitro. All these findings suggest that CA may prove to be an effective therapeutic agent for wear particle-induced osteolysis.

Hyperoxygenated Hydrogen-Rich Solution Suppresses Lung Injury Induced by Hemorrhagic Shock in Rats.

BACKGROUND: Hemorrhagic shock could induce acute lung injury (ALI), which is associated with cell hypoxia, lung tissue inflammation, free radical damage, and excessive cell apoptosis. Our previous studies demonstrated that hyperoxygenated solution could alleviate cell hypoxia. Furthermore, hydrogen-rich solution (HS) could relieve lung tissue inflammation, free radical damage and excessive cell apoptosis. Therefore we hypothesize that Hyperoxygenated Hydrogen-rich solution (HOHS) can protect the lung against ALI. MATERIALS AND METHODS: SD rats were randomly divided into five groups (n = 6 at each time point in each group) and were exposed to Hemorrhagic shock induced ALI, and then treated with lactated Ringer's solution (LRS), hyperoxygenated solution, HS, and HOHS, respectively. The protective effects of these solutions were assessed using methods as follows: arterial blood samples were collected for blood gas analysis; Bronchoalveolar lavage fluid was collected for cell count and protein quantification; lung tissue samples were collected to measure wet/dry ratio, as well as levels of T-SOD, MDA, TNF-α, and IL-6; Caspase-3 and TUNEL-positive cells, and pathological changes were observed under light microscope; ALI was scored using the Smith scoring method; ultrastructural changes of lung tissues were further observed with transmission electron microscopy. RESULTS: The results indicated that PaO2, PaCO2, and T-SOD increased in the three treatment groups (P < 0.05), most significantly in the HOHS group (P < 0.01) compared with the LRS group; and conversely that the levels of lactate, MDA, TNF-α and IL-6, cell count, protein content, caspase-3 and TUNEL-positive cells as well as ALI score decreased in the three treatment groups (P < 0.05), most significantly in the HOHS group (P < 0.01) compared with the LRS group. Morphological observation with optical microscope and electron microscopy showed that compared with the LRS group, cell damage in the three treatment groups improved to a varying extent, especially evident in the HOHS group. CONCLUSIONS: These findings demonstrate that HOHS can protect the lung against ALI induced by hemorrhagic shock.

MicroRNA-493 targets STMN-1 and promotes hypoxia-induced epithelial cell cycle arrest in G2/M and renal fibrosis.

Hypoxia plays an important role in the development of renal fibrosis. G2/M arrest in renal tubular cells is an important pathway in the development of chronic kidney disease. It is unknown whether hypoxia leads to renal fibrosis via the regulation of G2/M arrest in renal tubular epithelial cells. For the first time, to our knowledge, we showed that hypoxia induces G2/M arrest in renal tubular cells leading to renal fibrosis, and microRNAs are involved in this regulation. We compared microRNA expression between hypoxia and normoxia in HK2 cells and found microRNA (miR)-493 to be highly expressed at 24 and 48 h after hypoxia. The overexpression of miR-493 reduced the expression of the cell cycle regulator, Stathmin (STMN)-1, and increased the percentage of G2/M phase cells and profibrotic factors in HK2 cells. Targeting STMN-1 with short hairpin RNA produced an effect similar to that of miR-493 overexpression. On contrast, the miR-493 inhibitor reversed these effects in vitro. Consistent with these results, miR-493 sponge adeno-associated virus reduced the expression of profibrotic factors and increased STMN-1 in vivo. In summary, these results suggest that the miR-493-STMN-1 pathway contributes to hypoxia-induced tubular epithelial cell G2/M arrest and renal fibrosis. Abrogating G2/M arrest and blocking the miR-493-STMN-1 pathway will provide further insight for the development of antifibrosis therapy.-Liu, T., Liu, L., Liu, M., Du, R., Dang, Y., Bai, M., Zhang, L., Ma, F., Yang, X., Ning, X., Sun, S. MicroRNA-493 targets STMN-1 and promotes hypoxia-induced epithelial cell cycle arrest In G2/M and renal fibrosis.

The Effect of Anesthesia on the Immune System in Colorectal Cancer Patients.

Colorectal cancer (CRC) is the key leading cause of high morbidity and mortality worldwide. Surgical excision is the most effective treatment for CRC. However, stress caused by surgery response can destroy the body's immunity and increase the likelihood of cancer dissemination and metastasis. Anesthesia is an effective way to control the stress response, and recent basic and clinical research has shown that anesthesia and related drugs can directly or indirectly affect the immune system of colorectal cancer patients during the perioperative period. Thus, these drugs may affect the prognosis of CRC surgery patients. This review is intended to summarize currently available data regarding the effects of anesthetics and related drugs on perioperative immune function and postoperative recurrence and metastasis in CRC patients. Determining the most suitable anesthesia for patients with CRC is of utmost importance.

Hyperoxygenated hydrogen-rich solution suppresses shock- and resuscitation-induced liver injury.

BACKGROUND: It is not known whether simultaneous delivery of hydrogen and oxygen can reduce injury caused by hemorrhagic shock and resuscitation (HSR). This study investigated the therapeutic potential of hyperoxygenated hydrogen-rich solution (HHOS), a combined hydrogen/oxygen carrier, in a rat model of HSR-induced liver injury. MATERIALS AND METHODS: Rats (n = 60) were randomly divided into 5 groups (n = 6 per group at each time point). One group underwent sham operation, and the others were subjected to severe hemorrhagic shock and then treated with lactated Ringer's solution (LRS), hydrogen-rich solution, hyperoxygenated solution, or HHOS. At 2 and 6 h after resuscitation, blood samples (n = 6) were collected from the femoral artery and serum concentrations of alanine aminotransferase and aspartate aminotransferase (AST) were measured. Rats were then sacrificed, and histopathological changes in the liver were evaluated by quantifying the percentage of apoptotic cells by caspase-3 immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick-end labeling. Inflammation was assessed by assessing malondialdehyde content and tumor necrosis factor-α, and interleukin (IL)-6 expression. RESULTS: Compared to lactated Ringer's solution, hydrogen-rich solution, or hyperoxygenated solution groups, serum AST and alanine aminotransferase levels and IL-6, tumor necrosis factor-α, and malondialdehyde expression in liver tissue were decreased by HHOS treatment. The number of caspase-3- and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells was decreased (P < 0.05) by HHOS treatment, 2 and 6 h after resuscitation. CONCLUSIONS: HHOS has protective effects against liver injury in a rat model of HSR.