Catalytical feature of optical nanoprobes of boron nitride quantum dots in the presence of Cu2+ for the determination of dopamine.

Monitoring the concentration of dopamine (DA) is vital for preventing and diagnosing DA related diseases. In contrast to the traditional sensing methods for DA, in which direct or indirect effects on the optical probes are often recorded, a novel sensing concept is disclosed based on as a result of the in situ formation of polydopamine (PDA) originating from the synergetic effect between boron nitride quantum dots (BNQDs) and Cu2+. In the co-presence of BNQDs and Cu2+, DA was catalytically oxidized to PDA, accompanied by an obvious color change from colorless to brown. In contrast to previous reports, in which BNQDs have been employed as an optical probe, herein, the BNQDs not only acted as the optical energy donor, but also as the catalysts for the formation of PDA. The quenching efficiency resulting from the inner filter effect and the electron transfer between the BNQDs and PDA was directly proportional to the concentration of DA, ranging linearly from 2 to 80 µM with a limit of detection of 0.49 µM. The present system exhibited an outstanding selectivity for DA among other interfering coexisting biomolecules. Furthermore, the practical application of the proposed platform was verified by assaying DA in human plasma samples, and satisfactory recoveries ranging from 101.24% to 111.98% were obtained. With the satisfactory reliability, repeatability and stability, the proposed simple sensor showed significant potential for use in DA detection in other biomedical applications.

Increased ratio of ICOS(+) /PD-1(+) follicular helper T cells positively correlates with the development of human idiopathic membranous nephropathy.

To identify the frequencies of different subsets of peripheral blood follicular helper T (Tfh) cells in human idiopathic membranous nephropathy (IMN), 39 patients with new onset IMN and 18 age- and gender-matched healthy controls (HC) were enrolled for this study. The frequency of Tfh cells in venous blood were measured by flow cytometry, while concentration of serum IL-21 was detected by enzyme-linked immunosorbent assay. Correlation between the clinical features of IMN and Tfh cells was assessed by Spearman's rank correlation test. Overall, the frequencies of total, ICOS(+) , and PD-1(+) Tfh cells were increased in IMN patients, while the ratio of ICOS(+) /PD-1(+) Tfh cells positively correlated with IMN progression. However, the elevated serum IL-21 level in three subgroups of IMN patients, stratified based on 24-h urine protein levels, was not statistically significant compared to HC. Nonetheless, intracellular IL-21 in Tfh cells was generally increased in all IMN patients, and closely correlated with IMN development. Finally, the frequency of IL-21(+) Tfh cells and the ratio of ICOS(+) /PD-1(+) Tfh cells were positively correlated with the estimated 24-h urine protein of IMN patients. The data indicated that Tfh cells contribute to the pathogenicity of IMN. The ratio of ICOS(+) /PD-1(+) Tfh cells and the frequency of IL-21(+) Tfh cells may be indicators for evaluating the IMN development.

A higher frequency of IL-10-producing B cells in Hepatitis B virus-associated membranous nephropathy.

The purpose of this study is to elucidate the potential role of interleukin (IL)-10(+) regulatory B cells and other B cell subsets in the development of hepatitis B virus-associated membranous nephropathy (HBV-MN). A total of 14 patients with new onset HBV-MN, 12 individuals with immune-tolerant HBV infection (HBV-IT), and 12 healthy controls (HC) were examined for the percentages of CD38(+) , CD86(+) , CD27(+) , CD95(+) and IL-10(+) B cells by flow cytometry. Serum IL-10 concentration was examined by enzyme-linked immunosorbent assay (ELISA). The percentages of CD38(+) CD19(+) , CD86(+) CD19(+) , CD38(+) CD86(+) CD19(+) , and CD95(+) CD19(+) B cells were significantly higher in HBV-MN patients than the HBV-IT and HC. The percentages of CD5(+) CD19(+) , IL-10(+) CD19(+) B cells and serum IL-10 level in HBV-MN patients were significantly higher than the HC, and lower than the HBV-IT. Percentages of CD38(+) CD19(+) , and CD86(+) CD19(+) B cells were reduced after treatment, while the percentages of CD5(+) CD1d(+) CD19(+) , CD5(+) CD1d(+) IL-10(+) CD19(+) , and IL-10(+) CD19(+) B cells were increased. The 24 h urinary protein concentration was positively correlated with the percentage of CD38(+) CD19(+) , and negatively correlated with the percentage of IL-10(+) CD19(+) B cells and serum IL-10 level. Similarly, the value of eGFR was negatively correlated with the percentage of CD38(+) CD19(+) , and positively correlated with the percentage of IL-10(+) CD19(+) B cells and serum IL-10 level. Serum IL-10 level and the percentage of IL-10(+) CD19(+) were negatively correlated with the percentages of CD38(+) CD19(+) , and CD86(+) CD19(+) B cells. These results suggest that CD86(+) CD19(+) , CD38(+) CD86(+) CD19(+) , CD95(+) CD19(+) , and especially CD38(+) CD19(+) and IL-10(+) CD19(+) cells may participate in the pathogenesis of HBV-MN.

Up-regulation of miR-26a promotes neurite outgrowth and ameliorates apoptosis by inhibiting PTEN in bupivacaine injured mouse dorsal root ganglia.

Local anesthetic of bupivacaine may inhibit neurite outgrowth and induce apoptosis in mouse dorsal root ganglia (DRG) neurons. In this work, we intended to investigate the functional role of microRNA 26a (miR-26a) in regulating bupivacaine-induced nerve injury in DRG neurons. DRG neurons were extracted from C57BL/6 mice and cultured in vitro. Bupivacaine was applied in vitro and it induced apoptosis, inhibited neurite growth, and significantly down-regulated miR-26a gene in DRG neurons. MiR-26a mimic was then used to up-regulate miR-26a expression in DRG neurons. We found that miR-26a up-regulation promoted neurite outgrowth and reduced apoptosis in bupivacaine-injured DRG neurons. Luciferase assay and Western blot confirmed that Phosphatase and tensin homolog (PTEN) was down-stream target of miR-26a in DRG neurons. Ectopic PTEN up-regulation was then able to reverse the protective effect of miR-26a overexpression on bupivacaine-induced nerve injury in DRG neurons. Overall, this work demonstrated that miR-26a had a functional role in regulating bupivacaine-induced nerve injury in DRG neurons. Up-regulating miR-26a to suppress PTEN signaling pathway may be an effective method to protect local anesthetic-induced nerve injury in spinal cord.

Increased numbers of circulating ICOS⁺ follicular helper T and CD38⁺ plasma cells in patients with newly diagnosed primary biliary cirrhosis.

BACKGROUND: Aberrant activation of follicular helper T (TFH) and B cells is associated with the development of autoimmune diseases. However, little is known about the potential role of these cells in the development of primary biliary cirrhosis (PBC). AIM: This study aimed at characterizing the numbers of different subsets of circulating Tfh and B cells as well as evaluating their potential association with the levels of immunoglobulins and autoantibodies in newly diagnosed PBC patients. METHODS: The numbers of circulating CD27(+), CD38(+), CD86(+) and CD95(+) B cells as well as inducible T cell costimulator (ICOS)(+) and programmed death-1 (PD-1)(+), IL-21(+) TFH cells were examined in 58 patients with newly diagnosed PBC and 30 matched healthy controls (HCs). RESULTS: The numbers of circulating CD38(+)CD19(+), CD86(+)CD19(+), and CD95(+)CD19(+) B cells; CD3(+)CD4(+)CXCR5(+)ICOS(+) and CD3(+)CD4(+)CXCR5(+)PD-1(+) Tfh cells; and the levels of serum IL-21 in the PBC patients were significantly greater, but the numbers of CD27(+)CD19(+) B cells were significantly less than those in the HCs (p < 0.05). The numbers of CD3(+)CD4(+)CXCR5(+)ICOS(+) Tfh cells were positively correlated with the numbers of CD38(+)CD19(+) and CD86(+)CD38(+)CD19(+) B cells and the levels of serum anti-mitochondrial antibodies against M2 antigen (AMA-M2), AMA and immunolgubin M (IgM) in the PBC patients. The levels of serum IL-21 were positively correlated with the levels of serum AMA-M2, AMA, IgG and IgM, but negatively with the numbers of CD27(+)CD19(+) B cells in the PBC patients. CONCLUSIONS: Increased numbers of circulating ICOS(+) and IL-21(+) Tfh and CD38(+) plasma cells may be exhibited by patients with recent diagnoses of PBC.

Increased numbers of CD5+CD19+CD1dhighIL-10+ Bregs, CD4+Foxp3+ Tregs, CD4+CXCR5+Foxp3+ follicular regulatory T (TFR) cells in CHB or CHC patients.

BACKGROUND: IL-10+ regulatory B (Bregs), CD4+Foxp3+ regulatory T (Tregs), and CD4+CXCR5+Foxp3+ follicular regulatory T (TFR) cells regulate the progression of infection disease. This study aimed at examining how those cells associated with the development of chronic hepatitis B (CHB) and chronic hepatitis C (CHC) in a Chinese population. METHODS: The numbers of circulating IL-10+ Bregs, Tregs and TFR cells in 31 CHC, 58 CHB patients and 22 healthy controls (HC) were examined by flow cytometry. The potential association of those cells with clinical measures was analyzed. RESULTS: The numbers of CD5+CD19+CD1dhighIL-10+ Bregs, Tregs and TFR cells and the levels of serum IL-10, IFN-γ and IL-2 in the CHB, and IL-10 and IFN-γ in the CHC patients were significantly higher than that in the HC (p<0.05). Furthermore, the numbers of circulating IL-10+ Bregs and the levels of serum IL-10, but not other cytokines tested were positively correlated with the levels of serum HBV DNA and ALT in the HBeAg- CHB patients as well as HCV RNA and ALT in CHC patients. Additionally, the numbers of circulating TFR cells were positively correlated with the levels of serum HBV DNA and ALT in the CHB patients as well as HCV RNA and ALT in the CHC patients. CONCLUSIONS: Increased numbers of circulating IL-10+ Bregs and TFR cells are associated with poor virus eradication and liver injury in CHB and CHC patients. Furthermore, the levels of serum IL-10 is associated with the hepatic flares.

Echinacoside ameliorates D-galactosamine plus lipopolysaccharide-induced acute liver injury in mice via inhibition of apoptosis and inflammation.

OBJECTIVE: This study aimed to investigate the protective effects of echinacoside, one of the phenylethanoids isolated from the stems of Cistanche salsa, a Chinese herbal medicine, on D-galactosamine (GalN) and lipopolysaccharide (LPS)-induced acute liver injury in mice. METHODS: We administered GalN (650 mg/kg) together with LPS (30 µg/kg) to mice by intraperitoneal injection to induce acute liver damage. Echinacoside (60 mg/kg) was given intraperitoneally to mice at 1 h prior to GalN/LPS exposure. Mice were sacrificed at different time points following GalN/LPS treatment, and the liver and blood samples were collected for future analysis. RESULTS: It showed that GalN/LPS treatment produced severe hepatic injury, evidenced by significantly elevated plasma alanine aminotransferase (ALT) levels and abnormal histological changes such as hepatocyte necrosis or apoptosis, hemorrhage, fatty degeneration, and neutrophil infiltration. Notably, pretreatment with echinacoside remarkably improved the survival rate of GalN/LPS-treated mice and attenuated acute hepatotoxicity, as demonstrated by decreased ALT levels and improved histological signs. Echinacoside shows both anti-apoptotic and anti-inflammatory properties, characterized by a substantial inhibition of hepatocyte apoptosis and a significant reduction in the inflammatory markers, including myeloperoxidase, extracellular nucleosomes, high-mobility group box 1, and inflammatory cytokines in the plasma of mice, which may be important mechanisms related to its protective effect. CONCLUSION: Our results suggest that echinacoside can provide a pronounced protection against GalN/LPS-induced acute liver injury in mice, which may complement the available strategies for management of acute liver damage in clinical settings.

Anesthesia management experience for pediatric day-case PDA ligation under thoracoscopy assisted by a robot: a retrospective study.

BACKGROUND: To summarize the anesthesia management experience for pediatric day-case patent ductus arteriosus (PDA) ligation under robot-assisted thoracoscopy and explore the key points of anesthesia management for this procedure. METHODS: The clinical data of 72 pediatric patients who underwent robot-assisted thoracoscopic day-case PDA ligation at the Children's Hospital, Zhejiang University School of Medicine from April 2021 to February 2023 were retrospectively analyzed. 0.3% ropivacaine local infiltration combined with S-ketamine 0.2 mg/kg intravenous injection was used for postoperative analgesia The patient's basic information and intraoperative conditions were analyzed, which included gender, age, weight, surgery time, anesthesia time, extubation time, intraoperative blood loss, MAP before pneumothorax, PaCO2 before pneumothorax, etc. Postoperative conditions were also monitored, such as PACU stay time, agitation during the recovery period, pain, and the incidence of nausea and vomiting. After discharge, the recovery status was assessed. RESULTS: A total of 70 pediatric patients who met the criteria for day-case PDA ligation were included in this study. Before the occurrence of pneumothorax, the mean arterial pressure (MAP) of these 70 patients was 69.58 ± 12.52 mmHg, and during controlled hypotension, the MAP was 54.96 ± 11.23 mmHg. Before the occurrence of pneumothorax, the partial pressure of carbon dioxide (PaCO2) was 38.69 ± 3.38 mmHg, and during controlled hypotension, the PaCO2 was 51.42 ± 4.05 mmHg. Three cases experienced agitation during the recovery period, and four cases had mild pain, but there was no moderate or severe pain, nausea, or vomiting. Only 1 case of postoperative respiratory tract infection and 1 case of postoperative pneumothorax occurred. Within 30 days after discharge, the unplanned revisit rate, unplanned readmission rate, and surgical wound infection rate were all 0. The residual shunt rate detected by echocardiography was 0 after 1 month. CONCLUSIONS: The children under the robot-assisted thoracoscopic day case PDA surgeries in this study have limited trauma, little bleeding, and little postoperative pain, though still at a risk of respiratory infection and pneumothorax.

Effects of PYRIN-containing Apaf1-like protein 1 on isoflurane-induced postoperative cognitive dysfunction in aged rats.

Postoperative cognitive dysfunction (POCD) is a prevalent neurocognitive disorder following surgery and anesthesia, particularly in elderly patients. Isoflurane is a widely used anesthetic agent, which is associated with the development of POCD; however, the precise mechanisms remain unclear. In the present study, aged rats were exposed to 2% isoflurane to establish a POCD model. The expression of PYRIN­containing Apaf1­like protein 1 (PYPAF1) was knocked down using a lentivirus containing specific short hairpin RNA. Subsequently, the spatial learning ability of rats was assessed using the Morris water maze. In addition, mRNA and protein expression levels were detected using reverse transcription­quantitative PCR and western blot analysis, respectively. Immunofluorescence double staining was also used to determine the expression of PYPAF1 and Iba­1 in the hippocampus. Neural apoptosis was observed using TUNEL­NeuN double staining. The results revealed that isoflurane exposure impaired the spatial learning ability of rats, while PYPAF1 knockdown alleviated cognitive impairment. In addition, isoflurane exposure induced activation of the PYPAF1 inflammasome, as evidenced by elevated expression of PYPAF1 and apoptosis­associated speck­like protein containing a caspase recruitment domain, while silencing of PYPAF1 partially reversed this effect. Furthermore, isoflurane exposure promoted the activation of microglia and caspase­1, and the secretion of interleukin (IL)­1ß and IL­18, all of which were alleviated following PYPAF1 silencing. Moreover, isoflurane exposure induced neuronal apoptosis, elevated the levels of Bax and cleaved caspase­3, and inhibited the expression of Bcl­2; all of these effects were partially abrogated following PYPAF1 silencing. In conclusion, the results of the present study indicated that PYPAF1 silencing partially abolished isoflurane­induced cognitive impairment, neuroinflammation and neuronal apoptosis. Therefore, PYPAF1 may be a potential therapeutic target for treatment of POCD.

[Effect of propofol on synaptic long-term potentiation in hippocampal slices of rats].

OBJECTIVE: To investigate the effect of propofol on the synaptic long-term potentiation (LTP) in the CA(1) area of rats hippocampal slices and the possible mechanisms of its effect, and to elucidate the mechanisms underlying the effect of propofol on memory. METHODS: Hippocampal slices (400 microm thick) were obtained from male Sprague-Dawley rats (2 month old) that were ether-anesthetized and decapitated. The slices were prepared in artificial cerebrospinal fluid (ACSF), oxygenated with 95% O2 and 5% CO2. One glass electrode filled with superfusion solution was positioned in the pyramidal cell layer of the CA(1) area of rats hippocampal slices to simultaneously record evoked population spikes (PS). For LTP induction, high-frequency stimulation (HFS) conditioning pulses (100 Hz/1 s) were applied to the Schaffer collateral-commissural pathway of hippocampus using a bipolar stimulating electrode. The present study was performed to determine the effect of propofol at concentrations of 1 - 100 micromol/L on the LTP induction in rats hippocampal slices and to explore the functional importance of gamma-aminobutyric acid (GABA) type receptors in the effect of propofol on LTP induction. RESULTS: The amplitude of the PS in hippocampal slices of rats was significantly increased by 52% +/- 12% after HFS compared with that of pre-HFS. The amplitude of the PS was not significantly changed after HFS by perfusion of propofol at concentrations of 1, 5 micromol/L, when compared with the value in control group. The amplitude of the PS after HFS in the presence of propofol at 10, 30, 50 and 100 micromol/L was 124% +/- 9%, 112% +/- 8%, 106% +/- 7%, 102% +/- 6% respectively, which was significantly decreased compared with the control (all P < 0.01). The amplitude of the PS under perfusion with 50 micromol/L propofol after HFS in the presence of 50 micromol/L picrotoxin or 10 micromol/L bicuculline was 150% +/- 11%, 147% +/- 11% respectively, which was dramatically increased compared with the value of pre-HSF and 50 micromol/L propofol (all P < 0.01), but did not differ significantly from the control group. The amplitude of the PS under perfusion with 50 micromol/L propofol after HFS in the presence of 5 micromol/L CGP35348 has no significant difference compared with the value of pre-HSF and 50 micromol/L propofol, but it was significantly lower than that in the control group (P < 0.01). CONCLUSION: The inhibition of LTP induction in hippocampus of rats may contribute to propofol-induced deficits in memory, and the underlying mechanism is involved in the activation of GABA(A) receptor other than GABA(B) receptor.

MicroRNA-210 contributes to peripheral nerve regeneration through promoting the proliferation and migration of Schwann cells.

Peripheral nerve injury impacts the daily life of affected individuals. MicroRNA (miR)-210 is a multifunctional miR and has effects on the proliferation, migration and differentiation of cells. However, whether miR-210 has effects on peripheral nerve regeneration has remained elusive. In the present study, the miR-210 levels in a rat model of sciatic nerve injury were evaluated by reverse-transcription quantitative PCR and the effects of miR-210 on the proliferation and migration of Schwann cells were explored. Elevated miR-210 levels were discovered in the sciatic nerve injury rat model. miR-210 mimics were found to promote the proliferation and migration of Schwann cells, while miR-210 inhibitor was found to inhibit the proliferation and migration of Schwann cells. Further study showed that miR-210 had effects on the expression of growth-associated protein-43, myelin-associated glycoprotein and myelin basic protein. These results showed that miR-210 had effects on the proliferation and migration of Schwann cells and may be involved in the peripheral nerve regeneration.

Circulating memory T follicular helper subsets, Tfh2 and Tfh17, participate in the pathogenesis of Guillain-Barré syndrome.

Circulating memory T follicular helper subsets, Tfh2 and Tfh17 are found to be aberrantly regulated in many autoimmune diseases. However, their roles in the pathogenesis of GBS are still unclear. This study examined the phenotype, distribution, clinical relevance and potential function of Tfh2 and Tfh17 in 36 GBS patients (including 24 AMAN and 12 AIDP patients). We found that the absolute counts of total memory Tfh cells were significantly increased in AMAN, while no significant difference in AIDP compared with HC. Furthermore, the levels of the three subsets of memory Tfh cells, Tfh1, Tfh2 and Tfh17, were differentially altered in AMAN. The absolute counts of Tfh1, Tfh2 and Tfh17 were all increased to a higher level in AMAN. The ratio of (Tfh2+Tfh17)/Tfh1 and the percentages of ICOS(+) cells in Tfh2 and Tfh17 cells were greater in AMAN when compared to AIDP and HC, and the former had a positive correlation with the severity of both AMAN and AIDP. Conversely, the percentages of PD1(+) cells in Tfh2 and Tfh17 cells were lower in AMAN than in HC. Therefore, circulating memory Tfh2 and Tfh17 cells might promote the autoantibody-related immune response and serve as useful markers to evaluate the progression of AMAN.