An Aggregation-Induced Fluorescence Probe for Detection H2S and Its Application in Cell Imaging.

Monitoring hydrogen sulfide (H2S) in living organisms is very important because H2S acts as a regulator in many physiological and pathological processes. Upregulation of endogenous H2S concentration has been shown to be closely related to the occurrence and development of tumors, atherosclerosis, neurodegenerative diseases and diabetes. Herin, a novel fluorescent probe HND with aggregation-induced emission was designed. Impressively, HND exhibited a high selectivity, fast response (1 min) and low detection limit (0.61 µM) for H2S in PBS buffer (10 mM, pH = 7.42). Moreover, the reaction mechanism between HND and H2S was conducted by Job's plot, HR-MS, and DFT. In particular, HND was successfully employed to detect H2S in HeLa cells.

Cell-Cycle-related Protein Centromere Protein F Deficiency Inhibits Cervical Cancer Cell Growth by Inducing Ferroptosis Via Nrf2 Inactivation.

Cervical cancer (CC) is one of the severe cancers that pose a threat to women's health and result in death. CENPF, the centromere protein F, plays a crucial role in mitosis by regulating numerous cellular processes, such as chromosome segregation during mitosis. According to bioinformatics research, CENPF serves as a master regulator that is upregulated and activated in cervical cancer. Nevertheless, the precise biological mechanism that CENPF operates in CC remains unclear. The aim of this study was to analyze the function of CENPF on cervical cancer and its mechanism. We conducted immunohistochemistry and western blot analysis to examine the expression levels of CENPF in both cervical cancer tissues and cells. To explore the hidden biological function of CENPF in cell lines derived from CC, we applied lentivirus transfection to reduce CENPF manifestation. CENPF's main role is to regulate ferroptosis which was assessed by analyzing Reactive Oxygen Species (ROS), malonaldehyde (MDA), etc. The vitro findings were further validated through a subcutaneous tumorigenic nude mouse model. Our research finding indicates that there is an apparent upregulation of CENPF in not merely tumor tissues but also cell lines in the carcinomas of the cervix. In vitro and vivo experimental investigations have demonstrated that the suppression of CENPF can impede cellular multiplication, migration, and invasion while inducing ferroptosis. The ferroptosis induced by CENPF inhibition in cervical cancer cell lines is likely mediated through the Nrf2/HO-1 pathway. The data herein come up with the opinion that CENPF may have a crucial role in influencing anti-cervical cancer effects by inducing ferroptosis via the triggering of the Nrf2/HO-1 signaling pathway.

Daytime dysfunction may be associated with postoperative delirium in patients undergoing total hip/knee replacement: The PNDABLE study.

PURPOSE: Postoperative delirium (POD) is a usual complication after total hip/knee replacement, which may be affected by sleep characteristics. However, up to now, preoperative sleep characteristics have not been evaluated as risk factors of POD. The relationship between self-reported sleep characteristics and POD in patients has been investigated in this study. PATIENTS AND METHODS: We recruited 495 cognitively intact individuals in the final analysis from the Perioperative Neurocognitive Disorder and Biomarker Lifestyle study. Sleep characteristics were tested by the Pittsburgh Sleep Quality Index (PSQI). Mini-mental state examination was applied to assess preoperative mental status of patients. Postoperatively, we used confusion assessment method and memorial delirium assessment scale to evaluate the incidence of POD and POD severity, respectively. The cerebrospinal fluid (CSF) levels of T-tau, P-tau, Aß40, and Aß42 were detected by enzyme-linked immune-sorbent assay before the operation. Logistic regression, multiple linear regression, and mediation effects were performed to analyze the relationship between self-reported sleep characteristics and POD. RESULTS: POD was detected in 11.31% (56/495) of the patients, with logistic regression analysis showing that daytime dysfunction, P-tau, and T-tau were risk factors of POD, and Aß42 was a protective factor of POD. Multiple linear regression analysis confirmed that daytime dysfunction was positively correlated with P-tau in patients with POD. Meanwhile, compared to the patients with no postoperative delirium, the CSF levels of P- and T-tau were higher in patients with POD. Furthermore, mediation analysis showed that it was probable that daytime dysfunction mediated POD through P-tau (proportion: 12.90%) partially. CONCLUSION: Daytime dysfunction is a risk factor of POD preoperatively. To sum up, CSF P-tau protein might partially mediate the influence of daytime dysfunction on POD. CLINICAL TRIAL REGISTRATION: This study was registered at Chinese Clinical Trial Registry (ChiCTR2000033439).

A highly selective and sensitive turn-on fluorescent probe for the detection of Al3+ and its bioimaging.

A novel fluorescent sensor, 1-((2-hydroxynaphthalen-1-yl)methylene)urea (ocn) has been designed and applied as a highly selective and sensitive fluorescent probe for recognition of Al3+ in Tris-HCl (pH = 7.20) solution. The probe ocn exhibits an excellent selectivity to Al3+ over other examined metal ions, anions and amino acids with a prominent fluorescence 'turn-on' at 438 nm. ocn binds to Al3+ with a 2:1 binding stoichiometry and the detection limit was 0.3 µM. Furthermore, its capability of biological application was evaluated and the results showed that the sensor could be used to detect Al3+ in living cells.

A novel external catheter fixation method for chemotherapy using inferior epigastric arterial catheterization for cervical cancer.

The aim of this randomized controlled study was to investigate the effects of a novel external catheter fixation method for chemotherapy using inferior epigastric arterial catheterization for cervical cancer.Patients diagnosed with cervical cancer were randomly divided into a control group (n = 32) and a treatment group (n = 33). Patients in the control group underwent a traditional fixation method using a haemostat, elastic band and abdominal bandage. Patients in the treatment group underwent an improved fixation method using an indwelling needle and membrane cover. We used a visual analogue scale (VAS) to evaluate each patient's comfort score and also recorded the incidence of needlestick injury and the length of injection time in each group. The VAS scores measured before and after chemotherapy in the treatment group were lower than in the control group. The incidence of needlestick injury in the treatment group was significantly lower than in the control group. The length of injection time in treatment group was significantly lower than in the control group. Compared with the traditional fixation method, the improved fixation method not only increased patient comfort but also reduced both the risk of needlestick injury and the length of injection time. This improved technique deserves increased clinical use.

Isolation and identification of anti-tumor polysaccharide LSP21 from Limonium sinense (Girard) Kuntze.

Limonium sinense (Girard) Kuntze is a traditional Chinese folk medicine used for the treatment of fever, hemorrhage, hepatitis and other disorders. Recently, it was found that the crude polysaccharides from L. sinense (LSP) has significant anti-tumor activity. However, research on the isolation and identification of anti-tumor polysaccharide fractions from LSP has not yet been reported. In this study, three polysaccharides LSP11, LSP21, LSP31 were isolated and purified from LSP by using DEAE-52 cellulose column and Sephadex G-100 column chromatography. It was found that LSP21 exhibited the most significant inhibitory effect on the growth of HepG2 cells in vitro. Further research showed that LSP21 inhibited the growth of HepG2 cells in a dose-dependent manner and could induce cell body shrinkage, chromatin condensation, and reduction in the number of tumor cells with normal morphology which suggested that its cytotoxicity on tumor cell might be related to both inhibition on cell proliferation and inducement of cell death. Finally, the structural characteristics of LSP21 were analyzed by high performance liquid chromatography (HPLC) and gas chromatography (GC). The results showed that LSP21 is a heteropolysaccharide with an average molecular weight of 1.31×10(6) Da and consists of glucose, galactose and mannose in the ratio of 1.77:1:2.38.

Antitumor and immunomodulatory activity of polysaccharides from the root of Limonium sinense Kuntze.

Limonium sinense (Girard) Kuntze is a traditional Chinese folk medicine used for the treatment of fever, hemorrhage, hepatitis and other disorders. The study focused on the antitumor and immunomodulatory activities of L. sinense polysaccharides (LSP) which was obtained from the root of the plant. The antitumor effects of only LSP and LSP in combination with 5-fluorouracil (5-FU) were both evaluated with Heps-bearing tumor mice models. In addition, the macrophage phagocytosis assay, splenocyte proliferation and cytokines production tests were used to assess the immunomodulatory activities of LSP. The results revealed that the LSP (at the dose of 200 and 400 mg/kg) had an obvious inhibition on the growth of transplanted mouse tumor. It also exhibited a significant synergistic effect of antitumor activity when combined with 5-FU (p<0.05). Furthermore, the LSP (at the dose of 100 and 200 mg/kg) remarkably improved macrophage phagocytosis function in immune suppressed mice. In addition, LSP (at the dose of 50-200 µg/ml) showed significant synergistic effects on ConA-stimulated proliferation and IFN-γ and IL-2 production of splenocyte in vitro (p<0.05). These findings suggest that LSP had clear antitumor activity which might be related to its regulation of immune function in mice.

Preservation on calcium homeostasis is involved in mitochondrial protection of Limonium sinense against liver damage in mice.

Mechanisms underlying the mitochondrial protection of Limonium sinense extracts (LSE) was studied in lipopolysaccharide and D-galactosamine (LPS/D-GalN) intoxicated mice. It was found that increased activities of serum aspartate aminotransferase and alanine aminotransferase induced by LPS/D-GalN were significantly inhibited by pretreatment with LSE. The obvious disruption of membrane potential, intramitochondrial Ca (2+) overload and suppression in mitochondrial Ca (2+) -ATPase activity induced by LPS/D-GalN were significantly blocked by pretreatment with LSE. It was concluded that mechanisms underlying protection of LSE against liver mitochondria damage might be related to the preservation on mitochondrial Ca (2+) homeostasis through the preservation on mitochondrial Ca (2+) -ATPase activity.

Hepatoprotection of oleanolic acid is related to its inhibition on mitochondrial permeability transition.

The protective effects of oleanolic acid (OA) on carbon tetrachloride (CCl4)-induced liver mitochondrial damage and the possible mechanisms were investigated. Pretreatment with OA prior to the administration of CCl4 significantly suppressed the increases of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (4.2- and 19.9-fold, respectively) in a dose-dependent manner in mice. The dissipation of mitochondrial membrane potential (14.8%) and intra-mitochondrial Ca2+ overload (2.1-fold) in livers of CCl4-insulted mice were also dose-dependently prevented by pretreatment with 20, 50 or 100 mg/kg OA. In addition, the effects of OA on liver mitochondria permeability transition (MPT) induced by Ca2+ were assessed by measuring the change in mitochondrial membrane potential, release of matrix Ca2+ and mitochondrial swelling in vitro. The results showed that preincubation with 50 or 100 microg/ml OA obviously inhibited the Ca2+-induced mitochondrial swelling, mitochondrial membrane depolarization and intra-mitochondrial Ca2+ release. It could be concluded that OA has protective effects on liver mitochondria and the mechanisms underlying its protection may be related to its inhibitory action on MPT.

Inhibitory effect of TCCE on CCl4-induced overexpression of IL-6 in acute liver injury.

Terminalia catappa L. leaves have been shown to protect against acute liver injury produced by some hepatotoxicants, but the active components and mechanisms are not clear. This study was designed to characterize the protective effects of the chloroform fraction of the ethanol extract of T. catappa leaves (TCCE) against carbon tetrachloride (CCl4)-induced hepatotoxicity in mice, and analyze the changes in expression level of interleukin-6 (IL-6) in the process. It was found that TCCE pretreatment (10 or 30 mg/kg, ig) protected mice from CCl4 toxicity, as evidenced by the reversed alterations in serum alanine aminotransferase (sALT) and serum aspartate aminotransferase (sAST) activities. Additionally liver tissues were subjected to RT-PCR, Western blot and immunohistochemistry to analyze changes in IL-6 expression. It was found that TCCE markedly suppressed the CCl4-induced over-transcription of IL-6 gene. Consistent with the result, the expression of IL-6 protein was also blocked by TCCE in CCl4-stimulated mice, especially in the area around central vein on liver tissue section. In conclusion, TCCE is effective in protecting mice from the hepatotoxicity produced by CCl4, and the mechanisms underlying its protective effects may be related to the inhibition on the overexpression of IL-6 mainly around terminal hepatic vein.

Mechanisms of hepatoprotection of Terminalia catappa L. extract on D-Galactosamine-induced liver damage.

The hepatoprotective effects of the extract of Terminalia catappa L. leaves (TCE) against D-Galactosamine (D-GalN)-induced liver injury and the mechanisms underlying its protection were studied. In acute hepatic injury test, it was found that serum ALT activity was remarkably increased (3.35-fold) after injection of D-GalN in mice. But with oral pretreatment of TCE (20, 50 and 100 mg/kg/d) for 7days, change in serum ALT was notably reversed. In primary cultured hepatocytes from fetal mice, it was found that cell viability was decreased by 45.0% after addition of D-GalN, while incubation with TCE (0.1, 0.5 and 1.0 mg/ml) for 36 hours could prevent the decrease in a dose-dependent manner. Meanwhile, D-GalN-induced both the increase of AST level (1.9-fold) and the decrease of SOD activity (48.0%) in supernatant of primary cultured hepatocytes could also be inhibited by pretreatment with TCE. In order to study the possible mechanisms underlying its hepatoprotective effects, one effective component separated from TCE, 2alpha, 3beta, 23-trihydroxyursane-12-en-28-oic acid (DHUA), was used to determine anti-mitochondrial swelling activity and superoxide radicals scavenging activity in vitro. It was found that at the concentration range of 50-500 micromol/L DHUA, Ca2+ -induced mitochondrial swelling was dose-dependently inhibited, and superoxide radicals scavenging activity was also shown in a dose-dependent manner. It was concluded that TCE has hepatoprotective activity and the mechanisms underlying its protective effects may be related to the direct mitochondrion protection and strong scavenging activity on reactive oxygen species (ROS).

[Protective effect of the extract of Terminalia catappa leaves on acute liver injury induced by D-GalN in mice].

OBJECTIVE: To study the hepatoprotective effect of the extract of Terminala catappa leaves (TCE) and the possible mechanisms underlying its protection on acute liver injury induced by D-Galactosamine (D-GalN). METHOD: In vivo: D-GalN-induced liver injury model was used to evaluate the effect of TCE on the activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in mice. Structure of liver was observed and liver mitochondrial swelling was measured following D-GalN injection without or with TCE. In vitro: D-GalN-induced primary cultured hepatocytes injury model was used to value the effect of TCE on cultured hepatocytes. Cell viability was measured by means of MTT assay, and the AST and superoxide dismutase (SOD) activities in supernatant of cultured cells were investigated also. RESULT: In acute hepatic injury test, with oral pretreatment of TCE, remarkable rises in serum AST and ALT activities (2.95 fold and 3.35 fold) induced by D-GalN were obviously reversed and significant morphological changes were remarkably lessened. In addition, the decrease in sensitivity of mitochondrial swelling to the exotic Ca2+ stimulation induced by D-GalN was also prevented by TCE. In primary cultured hepatocytes of mice, it was found that incubation with TCE could prevent the decrease in cell viability in a dose-dependent manner. It was also found that both the increase in AST level (1.9 fold) and the decrease in SOD activity (48.0%) in supernatant of primary cultured hepatocytes induced by D-GalN could be inhibited by pretreatment of TCE. CONCLUSION: TCE has hepatoprotective activity and the mechanisms underlying its protective effect may be related to its antioxidant activity and protection on both hepatocytes and liver mitochondria.

[Hepatoprotective effects of chloroform extract from leaf of Terminalia catappa in relation to the inhibition of liver IL-6 expression].

OBJECTIVE: To study the hepatoprotective effects of Terminalia catappa chloroform extract (TCCE) and its effects on IL-6 gene over expression in liver of CCl4-treated mice. METHOD: Mice were orally pretreated with TCCE (20, 50, 100 mg x kg(-1) x d(-1)) for 5 days, and the sALT activity of mice was detected 24 hours after the intraperitoneal injection of CCl4 on the 5 th day. Meanwhile, IL-6 mRNA level was determined by using the method of RT-PCR. And the liver morphological changes were also observed. RESULT: sALT activity was remarkably increased (5.6 fold) after the injection of CCl4. However, with oral pretreatment of TCCE, changes in sALT were dose-dependently reversed. On the other hand, significant increase in IL-6 mRNA level induced by CCl4 was remarkably decreased. The level of IL-6 mRNA in 100 mg x kg(-1) TCCE treated mice was reversed to that of control. In addition, histological changes such as the infiltration of numerous inflammatory cells and hepatocyte swelling in injured mice were effectively lessened by the pretreatment of TCCE. CONCLUSION: TCCE has hepatoprotective activity and the mechanisms underlying its protective effects may be related to the inhibition on the over expression of IL-6 gene in liver.