Integrative analysis of transcriptomics and metabolomics reveals the protective effect and mechanism of salidroside on testicular ischemia-reperfusion injury.

Testicular torsion is a critical urologic condition for which testicular detorsion surgery is considered irreplaceable as well as the golden method of reversal. However, the surgical treatment is equivalent to a blood reperfusion process, and no specific drugs are available to treat blood reperfusion injuries. Salidroside (SAL) is one of the main effective substances in rhodiola, which has been shown to have antioxidant and antiapoptosis activities. This study was designed to determine whether SAL exerted a protective effect on testicular ischemia-reperfusion (I/R) injury. In this study, the I/R injury model of the testes and reoxygenation (OGD/R) model were used for verification, and SAL was administered at doses of 100 mg/kg and 0.05 mmol/L, respectively. After the experiments, the testicular tissue and TM4 Sertoli cells were collected for histopathologic and biochemical analyses. The results revealed that SAL improves the structure of testicular tissue and regulates the oxidation-antioxidation system. To further understand the molecular mechanisms of SAL in treating testicular I/R injuries, transcriptomics and metabonomics analyses were integrated. The results show that the Nfr2/HO-1/GPX4/ferroptosis signaling pathway is enriched significantly, indicating that it may be the main regulatory pathway for SAL in the treatment of testicular I/R injuries. Thereafter, transfection with Nrf2 plasmid-liposome was used to reverse verify that the Nfr2/HO-1/GPX4/ferroptosis signaling pathway was the main pathway for SAL anti-testicular I/R injury treatment. Thus, it is suggested that SAL can protect against testicular I/R injuries by regulating the Nfr2/HO-1/GPX4 signaling pathway to inhibit ferroptosis and that SAL may be a potential drug for the treatment of testicular I/R injuries.

Intramedullary nailing for pathological fractures of the proximal humerus caused by multiple myeloma: A case report and review of literature.

BACKGROUND: Multiple myeloma (MM) bone disease is indicative of MM, and reduces patient life quality. In addition to oncological, antineoplastic systemic therapy, surgical therapy in patients with MM is an essential treatment within the framework of supportive therapy measures and involves orthopedic tumor surgery. Nevertheless, there are few reports on intramedullary (IM) nailing in the treatment of MM-induced proximal humeral fracture to prevent fixation loss. We here describe a case of pathological fracture of the proximal humerus caused by MM successfully treated with IM nailing without removal of tumors and a review of the current literature. CASE SUMMARY: A 64-year-old male patient complaining of serious left shoulder pain and limited movement was admitted. The patient was finally diagnosed with MM (IgAλ, IIIA/II). After treatment of the pathological fracture with IM nailing, the patient's function recovered and his pain was rapidly relieved. Histopathological examination demonstrated plasma cell myeloma. The patient received chemotherapy in the Hematology Department. The humeral fracture displayed good union during the 40-mo follow-up, with complete healing of the fracture, and the clinical outcome was satisfactory. At the most recent follow-up, the patient's function was assessed using the Musculoskeletal Tumor Society score, which was 29. CONCLUSION: Early surgery should be performed for the fracture of the proximal humerus caused by MM. IM nailing can be used without removal of tumors. Bone cement augmentation for bone defects and local adjuvant therapy can also be employed.

Pyruvate as a novel carrier of hydroxyethyl starch 130/0.4 may protect kidney in rats subjected to severe burns.

BACKGROUND: The carrier of hydroxyethyl starch (HES) may play a critical role in kidney injury in fluid resuscitation. This study aimed mainly to compare effects of pyruvate-enriched saline with normal saline (NS) and acetate Ringer's (AR) solution as a carrier in HES130/0.4 on kidney function in rats subjected to severe burns. METHODS: Using a lethal burn model, 140 rats were randomly allocated in seven groups (n = 20): sham group (group S); no fluid after burn (group N); burn resuscitated with NS (group NS); burn resuscitated with pyruvate saline (group PS); burn resuscitated with AR plus pyruvate-HES (group SP); burn resuscitated with AR plus acetate-HES (group SA), and burn resuscitated with AR plus NS-HES (group SN). A low volume (18.75 mL·kg-1 during 12 h) of HES130/0.4 was infused with the ratio of 1:1 to crystalloids. Renal surface blood flow, blood creatinine and blood urea nitrogen, early sensitive indicators of kidney function: alpha-1 microglobulin, cystatin-C, and neutrophil gelatinase-associated lipocalin in blood and urine, and kidney tissue water contents were determined. Renal histopathological alterations with Paller scores were also measured at 8 h and 24 h after burn (n = 10), respectively. RESULTS: The results showed in a comparable manner that group SP was the best in three HES groups and group PS was superior to group NS in renal preservation; group SP appeared significantly beneficial compared with group PS in renal surface blood flow, cystatin-C, neutrophil gelatinase-associated lipocalin, water contents, and Paller scores at 8-h or both time points after burn, respectively (all P < 0.05). CONCLUSIONS: The carrier of HES130/0.4 played a crucial role in kidney injury in fluid resuscitation of rats subjected to severe burns. Pyruvate-enriched HES130/0.4 was superior and HES130/0.4, per se, might be not renocytotoxic, but renoprotective. Further studies are warranted.

Pyruvate in oral rehydration salt improves hemodynamics, vasopermeability and survival after burns in dogs.

BACKGROUND: To investigate whether pyruvate-enriched oral rehydration solution (Pyr-ORS), compared with citrate-enriched ORS (Cit-ORS), improves hemodynamics and organ function by alleviating vasopermeability and plasma volume loss during intra-gastric fluid rehydration in dogs with severe burn. METHODS: Forty dogs subjected to severe burn were randomly divided into four groups (n=10): two oral rehydrated groups with Pyr-ORS and Cit-ORS (group PR and group CR), respectively, according to the Parkland formula during the first 24h after burns. Other two groups were the intravenous (IV) resuscitation (group VR) with lactated Ringer's solution with the same dosage and no fluid rehydration (group NR). During the next 24h, all groups received the same IV infusion. The hemodynamics, plasma volume, vasopermeability and water contents and function of various organs were determined. Plasma levels of vascular endothelial growth factor (VEGF) and platelet activating factor (PAF) were detected by ELISA. RESULTS: Hemodynamics parameters were significantly improved in group PR superior to group CR after burns. Levels of VEGF and PAF were significantly lower in group PR than in group CR. Organ function parameters were also greatly preserved in group PR, relative to groups CR and NR. Lactic acidosis was fully corrected and survival increased in group PR (50.0%), compared to group CR (20.0%). CONCLUSION: Pyr-ORS was more effective than Cit-ORS in improving hemodynamics, visceral blood perfusion and organ function by alleviating vasopermeability-induced visceral edema and plasma volume loss in dogs with severe burn.

Dimethyl sulfoxide inhibits zymosan-induced intestinal inflammation and barrier dysfunction.

AIM: To investigate whether dimethyl sulfoxide (DMSO) inhibits gut inflammation and barrier dysfunction following zymosan-induced systemic inflammatory response syndrome and multiple organ dysfunction syndrome. METHODS: Sprague-Dawley rats were randomly divided into four groups: sham with administration of normal saline (SS group); sham with administration of DMSO (SD group); zymosan with administration of normal saline (ZS group); and zymosan with administration of DMSO (ZD group). Each group contained three subgroups according to 4 h, 8 h, and 24 h after surgery. At 4 h, 8 h, and 24 h after intraperitoneal injection of zymosan (750 mg/kg), the levels of intestinal inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10] and oxides (myeloperoxidase, malonaldehyde, and superoxide dismutase) were examined. The levels of diamine oxidase (DAO) in plasma and intestinal mucosal blood flow (IMBF) were determined. Intestinal injury was also evaluated using an intestinal histological score and apoptosis of intestinal epithelial cells was determined by deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The intestinal epithelial tight junction protein, ZO-1, was observed by immunofluorescence. RESULTS: DMSO decreased TNF-α and increased IL-10 levels in the intestine compared with the ZS group at the corresponding time points. The activity of intestinal myeloperoxidase in the ZS group was higher than that in the ZD group 24 h after zymosan administration (P < 0.05). DMSO decreased the content of malondialdehyde (MDA) and increased the activity of superoxide dehydrogenase (SOD) 24 h after zymosan administration. The IMBF was lowest at 24 h and was 49.34% and 58.26% in the ZS group and ZD group, respectively (P < 0.05). DMSO alleviated injury in intestinal villi, and the gut injury score was significantly lower than the ZS group (3.6 ± 0.2 vs 4.2 ± 0.3, P < 0.05). DMSO decreased the level of DAO in plasma compared with the ZS group (65.1 ± 4.7 U/L vs 81.1 ± 5.0 U/L, P < 0.05). DMSO significantly preserved ZO-1 protein expression and localization 24 h after zymosan administration. The TUNEL analysis indicated that the number of apoptotic intestinal cells in the ZS group was much higher than the ZD group (P < 0.05). CONCLUSION: DMSO inhibited intestinal cytokines and protected against zymosan-induced gut barrier dysfunction.

Pyruvate-enriched oral rehydration solution improved intestinal absorption of water and sodium during enteral resuscitation in burns.

AIM: To investigate alteration in intestinal absorption during enteral resuscitation with pyruvate-enriched oral rehydration solution (Pyr-ORS) in scalded rats. METHODS: To compare pyruvate-enriched oral rehydration solution (Pyr-ORS) with World Health Organisation oral rehydration solution (WHO-ORS), 120 rats were randomly divided into 6 groups and 2 subgroups. At 1.5 and 4.5 h after a 35% TBSA scald, the intestinal absorption rate, mucosal blood flow (IMBF), Na(+)-K(+)-ATPase activity and aquaporin-1 (AQP-1) expression were determined (n = 10), respectively. RESULTS: The intestinal Na(+)-K(+)-ATPase activity, AQP-1 expression and IMBF were markedly decreased in scald groups, but they were profoundly preserved by enteral resuscitation with WHO-ORS and further improved significantly with Pyr-ORS at both time points. Na(+)-K+-ATPase activities remained higher in enteral resuscitation with Pyr-ORS (Group SP) than those with WHO-ORS (Group SW) at 4.5 h. AQP-1 and IMBF were significantly greater in Group SP than in Group SW at both time points. Intestinal absorption rates of water and sodium were obviously inhibited in scald groups; however, rates were also significantly preserved in Group SP than in Group SW with an over 20% increment at both time points. CONCLUSION: The Pyr-ORS may be superior to the standard WHO-ORS in the promotion of intestinal absorption of water and sodium during enteral resuscitation.

Transfer of dipolar gas through the discrete localized mode.

By considering the discrete nonlinear Schrödinger model with dipole-dipole interactions for dipolar condensate, the existence, the types, the stability, and the dynamics of the localized modes in a nonlinear lattice are discussed. It is found that the contact interaction and the dipole-dipole interactions play important roles in determining the existence, the type, and the stability of the localized modes. Because of the coupled effects of the contact interaction and the dipole-dipole interactions, rich localized modes and their stability nature can exist: when the contact interaction is larger and the dipole-dipole interactions is smaller, a discrete bright breather occurs. In this case, while the on-site interaction can stabilize the discrete breather, the dipole-dipole interactions will destabilize the discrete breather; when both the contact interaction and the dipole-dipole interactions are larger, a discrete kink appears. In this case, both the on-site interaction and the dipole-dipole interactions can stabilize the discrete kink, but the discrete kink is more unstable than the ordinary discrete breather. The predicted results provide a deep insight into the dynamics of blocking, filtering, and transfer of the norm in nonlinear lattices for dipolar condensates.

[Mechanism of signal transduction of differentiation of mesenchymal stem cells into cytokeratin-expressing epidermoid cells].

OBJECTIVE: To investigate the role of the signal routes P38, ERK, and Rho in the differentiation of bone marrow mesenchymal stem cells (MSCs) into epidermoid cells. METHODS: (1) MSCs were separated from the bone marrow of Wistar rats by Ficoll-Pague lymphocyte separating medium and proliferated in culture medium. Then the MSCs were immunocytochemically stained to detect the expression of surface antigens. (2) The MSCs were randomly divided into 3 groups: control group; pure induction induced group, cultured with epithelial growth factor (EGF) added into the culture fluid, and Rho inhibition group, cultured with EGF and HA1077, a ROK inhibitor, added into the culture fluid. One, 3, 5, and 7 days later FC was used to detect the levels of phosphorylated P38 and ERK. (3) MSCs were randomly divided into 4 groups: control group, cultured with low-sugar DMEM complete culture fluid; pure induction group, cultured with supernatant of rat fibroblasts and EGF added into the culture fluid, p38 blocking group, with SB203580, inhibitor of P38 added into the culture fluid; and ERK blocking group, with PD98059, inhibitor of ERK added into the culture fluid. Seven days later, SP method was used to detect the expression of CK5/8 and CK19 induced by MSCs. (4) MSCs were randomly divided into 4 groups: control group; pure induction group, with supernatant of rat fibroblasts and EGF added into the culture fluid; and RHO blocking group, with HA1007 added into the culture fluid. Seven days later, FC was used to detect the expression of CK5/8 and CK19. RESULTS: (1) Both FC and immunocytochemistry showed that the MSCs were uniformly positive in CD29 and CD44, but did not express CD34 and CD45. (2) The phosphorylated P38 rate remained 0.01% in the control group. The phosphorylated P38 rate was 0.04%, significantly higher than that of the control group (0.01%, P < 0.05) at day 5, and then lowered to 0.01% at day 5 in the pure induction group; and became 6.17%, 4.13%, 3.97%, and 0.41% respectively at day 1, 3, 5, and 7, all significantly higher than those of the control group (all P < 0.05), in the Rho inhibition group. The phosphorylated ERK level was 4.23% in the control group; became 0.39% and 0.40% at day 3 and day 5 (both P < 0.05), and then returned to 5.10% at day 7 in the pure induction group; and was not significantly changed at days 1, 3, and 5, and then became 0.41%, significantly lower than that of the control group (P < 0.05), in the Rho blocking group, (3) The control group was CK5/8 and CK19 negative. The CK5/8 and CK19 rates at day 7 of the pure induction group were 3.01% and 6.47% respectively, both significantly higher than those of the p38 inhibition group (1.43% and 5.41% respectively, both P < 0.05). The CK5/8 and CK19 expression rates of the ERK inhibition group were 5.54% and 7.56% respectively, both significantly higher than those of the pure induction group (both P < 0.05), (4) The CK5/8 and CK19 expression rates of the HA1077 group were 21.65% and 39.41% pure, both significantly higher than those of the pure induction group (1.81% and 10.19% respectively, both P < 0.05). CONCLUSION: p38 route may play an active role in the differentiation of MSCs into epidermoid cells. Blocking of the upstream signal Rho may enhance the activation of p38 route and then promote the differentiation of MSCs into epidermoid cells.

[Cellular phenotype conversion induced by co-culture of human mesenchymal stem cells cocultured with human sweat gland cells].

OBJECTIVE: To investigate the cellular phenotype conversion during human mesenchymal stem cells (hMSCs) cocultured with injured human sweat gland cells (hSGCs) in vitro. METHODS: HMSCs and hSGCs were isolated and cultured and expanded respectively. The antigens expression of hMSCs and hSGCs were detected by two-steps immunocytochemistry. HMSCs were labeled with BrdU. The hSGCs were heat-shocked at 47 degrees C for 40 min when they reached 70% confluency, then cooled for 1-2 h at 37 degrees C and (1 - 2) x 10(5) BrdU-labeled hMSCs were added before incubation for up to 2 weeks. The cocultures were observed by phase contrast microscopy and detected by double-staining immunocytochemistry using CEA and BrdU as primary antibodies. RESULTS: The cultured hMSCs and hSGCs were clonogenic growth. HMSCs were positive for anti-CD44 and anti-CD105 staining and negative for anti-CD34 and anti-CEA staining. HSGCs express CK7, CK18, CK19 and CEA. The positive rate of BrdU labeled-hMSCs was 90%. The majority of hSGCs lost cell-cell contact after heat-shock. 2 weeks after cocultured, some cocultured cells were positive for both anti-CEA and anti-BrdU staining and some cocultures had more than two nuclei which stained with two different colors by double-staining immunocytochemistry. Statistic results showed 1%-5% of the hMSCs added to the coculture system were recovered as double-staining cells expressing BrdU and CEA while only 0.01%-0.05% cells stained with two different colors in nuclei. The multi-nucleated cells were wide and flatten. CONCLUSION: HMSCs could differentiate into hSGCs in vitro under injured microenvironment. The mechanisms of which may be that hMSCs differentiate into hSGCs directly or by cell fusion, even nucleus fusion.