Melatonin inhibits senescence-associated melanin pigmentation through the p53-TYR pathway in human primary melanocytes and the skin of C57BL/6 J mice after UVB irradiation.

UVB exposure accelerates skin aging and pigmentation. Melatonin effectively regulates tyrosinase (TYR) activity and aging. The purpose of this study was to determine the association between premature senescence and pigmentation, and the mechanism of melanin synthesis effected by melatonin. Primary melanocytes were extracted and identified from the male foreskin. To inhibit TYR expression, primary melanocytes were transduced with the lentivirus pLKD-CMV-EGFP-2A-Puro-U6-TYR. The wild-type TYR(+/+) and TYR(-/-) or TYR(+/-) knockout C57BL/6 J mice were used to determine the role of TYR on melanin synthesis in vivo. Results showed that UVB-induced melanin synthesis is dependent on TYR in primary melanocytes and mice. Furthermore, in primary melanocytes pretreated with Nutlin-3 or PFT-α to up or downregulate p53, results showed that premature senescence and melanin synthesis increased in primary melanocytes after UVB irradiation at 80 mJ/cm2, and further increased after being treated with Nutlin-3, while significantly decreased with PFT-α. In addition, melatonin inhibited UVB-induced premature senescence associated with inactivation of p53 and phosphorylation of p53 on Ser15 (ser-15), a decrease of melanin synthesis accompanied by reduced TYR expression. Moreover, skin erythema and pigmentation induced by UVB were reduced in the dorsal and ear skin of mice topically pretreated with 2.5% melatonin. These indicate that melatonin inhibits UVB-induced senescence-associated pigmentation via the p53-TYR pathway in primary melanocytes and prevents pigmentation obviously in the dorsal and ear skin of C57BL/6 J mice after UVB irradiation. KEY MESSAGES: P53 links UVB irradiation-induced senescence and senescence-associated pigmentation and regulates TYR in primary melanocytes after UVB irradiation. Melatonin inhibits senescence-associated pigmentation through the p53-TYR pathway in primary melanocytes. Melatonin prevents skin erythema and melanin pigmentation induced by UVB irradiation in the dorsal and ear skin of C57BL/6J mice.

Microglial voltage-dependent anion channel 1 signaling modulates sleep deprivation-induced transition to chronic postsurgical pain.

STUDY OBJECTIVES: This study verified that sleep deprivation before and after skin/muscle incision and retraction (SMIR) surgery increased the risk of chronic pain and investigated the underlying roles of microglial voltage-dependent anion channel 1 (VDAC1) signaling. METHODS: Adult mice received 6 hours of total sleep deprivation from 1 day prior to SMIR until the third day after surgery. Mechanical and heat-evoked pain was assessed before and within 21 days after surgery. Microglial activation and changes in VDAC1 expression and oligomerization were measured. Minocycline was injected to observe the effects of inhibiting microglial activation on pain maintenance. The VDAC1 inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and oligomerization inhibitor VBIT-4 were used to determine the roles of VDAC1 signaling on microglial adenosine 5' triphosphate (ATP) release, inflammation (IL-1ß and CCL2), and chronicity of pain. RESULTS: Sleep deprivation significantly increased the pain duration after SMIR surgery, activated microglia, and enhanced VDAC1 signaling in the spinal cord. Minocycline inhibited microglial activation and alleviated sleep deprivation-induced pain maintenance. Lipopolysaccharide (LPS)-induced microglial activation was accompanied by increased VDAC1 expression and oligomerization, and more VDAC1 was observed on the cell membrane surface compared with control. DIDS and VBIT-4 rescued LPS-induced microglial ATP release and IL-1ß and CCL2 expression. DIDS and VBIT-4 reversed sleep loss-induced microglial activation and pain chronicity in mice, similar to the effects of minocycline. No synergistic effects were found for minocycline plus VBIT-4 or DIDS. CONCLUSIONS: Perioperative sleep deprivation activated spinal microglia and increases the risk of chronic postsurgical pain in mice. VDAC1 signaling regulates microglial activation-related ATP release, inflammation, and chronicity of pain.

Construction of Zeolite-Loaded Fluorescent Supramolecular on-off Probes for Corrosion Detection Based on a Cation Exchange Mechanism.

Metal engineering structures are commonly covered and protected by coatings. However, the early local corrosion under the coatings and at defects is difficult to detect and discover. Visibility to the naked eye means that corrosion has already developed and expanded. Therefore, it is practical significant to detect the early corrosion of coated metal. Based on the formation of iron ions and anodic acidification in the local corrosion process, iron ions and proton responsive fluorescent rhodamine B acylhydrazone on-off probes are prepared by newly improved methods and denoted as RBA. RBA are loaded on the surface and in the lattice cage of zeolite (ZEO) to protect RBA from premature exposure to the corrosive environment and fluorescence quenching. In corrosive environments, the RBA loaded on the surface are released and complex with iron ions in the environment to activate fluorescence characteristics. Simultaneously, due to the cation exchange of ZEO, iron ions enter the lattice cage of ZEO and combine with RBA in the lattice cage to turn on fluorescence. When applied in epoxy coatings, the RBA/ZEO effectively indicate the occurrence of corrosion under the coatings and at defects, and accurately locate the corrosion site. Nano-scale ZEO (or RBA/ZEO) fill the micropores such as pinholes and defects of the coatings, and increase the difficulty of diffusion and penetration of corrosive media into the coatings. The application of RBA/ZEO functional filler not only do not weaken the main anti-corrosion performance of the coatings, but also significantly improve it.

Low vitamin D levels are associated with cognitive impairment in patients with Hashimoto thyroiditis.

BACKGROUND: Cognitive impairment is commonly observed in patients with Hashimoto thyroiditis (HT). Low levels of vitamin D have been correlated with cognitive impairment in non-HT population. We examined the association of vitamin D levels with cognitive impairment in patients with HT. METHODS: We recruited 194 patients with HT and 200 healthy volunteers. Levels of serum 25-hydroxyvitamin D (25(OH)D) were measured using a competitive protein-binding assay. Cognitive funtion was assessed using Montreal Cognitive Assessment score (MoCA). Subjects with a MoCA scores < 26 are considered as having mild cognitive impairment (MCI). Multivariate analysis was performed using logistic regression models. RESULTS: Fifty-five HT patients (28.4%) were diagnosed as having MCI. Patients with MCI had significantly lower 25(OH)D levels when compared with patients without MCI (33.9 ± 6.2 vs. 44.3 ± 9.6 nmol/L, P < 0.001). Significant differences in 25(OH)D quartiles of HT patients were observed between the patients with MCI and the patients without MCI (P < 0.001). In multivariate analyses, serum 25(OH)D levels (≤ 34.0 and ≥ 47.1 nmol/L) were significantly associated with cognitive impairment in patients with HT (OR 6.279, 95% CI 2.673-14.834, P < 0.001; OR 0.061, 95% CI 0.008-0.491, P = 0.009, respectively). CONCLUSION: Our results demonstrate an important association between serum vitamin D levels and cognitive impairment in patients with HT.

[Analgesic and Sedative Effect of Acupuncture Combined with Medicine on Patients Undergiong Cardiac Surgery].

OBJECTIVE: To observe analgesic and sedative effect of acupuncture combined with medicine (ACM) on patients undergiong cardiac surgery. METHODS: A total of 50 patients with cardiac surgery from January 2012 to October 2014 were randomly assigned to the conventional analgesia group (group A) and the ACM analgesia group (group B), 25 in each group. Patients in group A were subjected to analgesia and sedation by injecting dexmedetomidine, while patients in group B were subjected to analgesia and sedation by electro-acupuncture [EA, Shenting (GV24); Yintang (EX-HN3)] combined with injection of dexmedetomidine. Morphine hydrochloride injection was performed when analgesia and sedation effect was ineffective in the two groups. The indicators of patients at different time points in the two groups were observed, such as static and dynamic VAS scores, SAS scores, mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SpO2). The injection dosage of dexmedetomidine and morphine hydrochloride, analgesia satisfaction rate, sedation satisfaction rate, the incidences of adverse reactions during treatment such as bradycardia and low blood pressure, mechanical ventilation time, ICU time, and hospitalization expense were observed and recorded in the two groups. RESULTS: There was no statistical difference in static and dynamic VAS scores, SAS score, MAP, HR and SpO2 between the two groups at different time points (P > 0.05). The injection dosage of dexmedetomidine and morphine hydrochloride was significantly reduced in group B than in group A (P < 0.05). The analgesia satisfaction rate of patients in group B was much higher than that in group A (P < 0.05). The incidence of bradycardia also obviously decreased more in group B than in group A (P < 0.05). There was no statistical difference in patients' sedation satisfaction rate, incidences of low blood pressure, delirium, vomiting; mechanical ventilation time, ICU time, or hospitalization expense between the two groups (P > 0.05). CONCLUSION: The analgesia method of ACM could reduce the dosage of traditional analgesic drugs and the occurrence of partial adverse reactions.

Treatment of thoracic hemorrhage due to rupture of traumatic mediastinal hematoma.

Patients in traffic accidents are usually presented with pain and bleeding due to fractures or soft tissue injury. On some occasions, more severe complications may be triggered by the trauma. A review of the published English language literature reveals no survival case once the traumatic mediastinal hematoma is ruptured. In our case, a 54-year-old man suffering motorcycle accident was admitted to emergency department. Computed tomography scan revealed subdural hematoma combined with posterior mediastinal hematoma. The patient was saved and discharged with a satisfactory outcome. Here we hope to share our treatment experience in dealing with the patient with severe multiple trauma.

[The observations of curative efficacy of rhubarb combined with blood purification on treatment patients with severe acute organophosphorus pesticide poisoning].

OBJECTIVE: To observe the curative efficacy of rhubarb, montmorillonite powder combined with blood purification on treatment for patients with severe acute organophosphorus pesticide poisoning (AOPP). METHODS: 39 patients with AOPP were divided into treatment group (received the combined treatment of rhubarb, montmorillonite powder and blood purification on the basis of routine therapy, n = 21) and control group (only received the routine treatment because of financial difficulties or the will of family members, n = 18). The differences of clinical manifestations, curative effects and prognosis between two groups were compared. RESULTS: The time of consciousness recovery, the duration of mechanical ventilation and the length of stay in hospital in treatment group were (6.5 ± 1.3), (7.9 ± 2.0) and (13.1 ± 3.2) days, which were significantly shorter than those [(8.4 ± 2.4), (10.7 ± 2.9) and (16.5 ± 3.7) days] of control group (P < 0.05). In 5, 6 and 7 day after treatment,the cholinesterase (ChE) activities of treatment group were significantly higher than those of control group (P < 0.05). The total amount and using time of atropine and pyraloxime methylchloride in treatment group were significantly smaller and shorter than those in control group (P < 0.05). The death rate of treatment group was [19.0% (4/21)], which were significantly lower than that of control group [19.0% (4/21)] (P < 0.05). CONCLUSION: The combined treatment of rhubarb, montmorillonite powder and blood purification of the AOPP patients has a better curative effect.

[Synthesis and antibacterial activities of 7-{4-[2-[2-substituted-4-((5S)-5-acetylaminomethyl-2-oxo-oxazolidin-3-yl)}-phenyl] -ethyl]-piperazin-1-yl}-fluoroquinolones].

AIM: To find out new oxazolidinone-fluoroquinolone derivatives with high antibacterial activity. METHODS: Some 7-{4-[2-[2-substituted-4-((5S)-5- acetylaminomethyl-2-oxo-oxazolidin-3-yl)-phenyl]-ethyl]-piperazin-1-yl}-fluoroquinolones were designed and synthesized, and their antibacterial activities were tested in vitro. RESULTS: Twenty target compounds were obtained and their structures were confirmed by 1H NMR and MS. The target compounds had high antibacterial activities in vitro, especially, the activity of compound 22 against Enterococcus faecium was 16-fold and 64-fold more potent than that of linezolid and norfloxacin, respectively, and its MIC value against Staphylococcus aureus was 4-fold lower than that of linezolid. CONCLUSION: The oxazolidinone-fluoroquinolone derivatives improved the antibacterial activities.