Hypoxia preconditioned DPSC-derived exosomes regulate angiogenesis via transferring LOXL2.

Hypoxia was proved to enhance the angiogenesis of stem cells. However, the mechanism of the angiogenic potential in hypoxia-pretreated dental pulp stem cells (DPSCs) is poorly understood. We previously confirmed that hypoxia enhances the angiogenic potential of DPSC-derived exosomes with upregulation of lysyl oxidase-like 2 (LOXL2). Therefore, our study aimed to illuminate whether these exosomes promote angiogenesis via transfer of LOXL2. Exosomes were generated from hypoxia-pretreated DPSCs (Hypo-Exos) stably silencing LOXL2 after lentiviral transfection and characterized with transmission electron microscopy, nanosight and Western blot. The efficiency of silencing was verified using quantitative real-time PCR (qRT-PCR) and Western blot. CCK-8, scratch and transwell assays were conducted to explore the effects of LOXL2 silencing on DPSCs proliferation and migration. Human umbilical vein endothelial cells (HUVECs) were co-incubated with exosomes to assess the migration and angiogenic capacity through transwell and matrigel tube formation assays. The relative expression of angiogenesis-associated genes was characterized by qRT-PCR and Western blot. LOXL2 was successfully silenced in DPSCs and inhibited DPSC proliferation and migration. LOXL2 silencing in Hypo-Exos partially reduced promotion of HUVEC migration and tube formation and inhibited the expression of angiogenesis-associated genes. Thus, LOXL2 is one of various factors mediating the angiogenic effects of Hypo-Exos.

A loss-of-function variant in ZCWPW1 causes human male infertility with sperm head defect and high DNA fragmentation.

BACKGROUND: Male infertility is a global health issue. The more causative genes related to human male infertility should be further explored. The essential role of Zcwpw1 in male mouse fertility has been established and the role of ZCWPW1 in human reproduction needs further investigation to verify. METHODS: An infertile man with oligoasthenoteratozoospermia phenotype and his parents were recruited from West China Second University Hospital, Sichuan University. A total of 200 healthy Han Chinese volunteers without any evidence of infertility were recruited as normal controls, while an additional 150 infertile individuals were included to assess the prevalence of ZCWPW1 variants in a sporadic male sterile population. The causative gene variant was identified by Whole-exome sequencing and Sanger sequencing. The phenotype of the oligoasthenoteratozoospermia was determined by Papanicolaou staining, immunofluorescence staining and electron microscope. In-vitro experiments, western blot and in-silicon analysis were applied to assess the pathogenicity of the identified variant. Additionally, we examined the influence of the variant on the DNA fragmentation and DNA repair capability by Sperm Chromatin Dispersion and Neutral Comet Assay. RESULTS: The proband exhibits a phenotype of oligoasthenoteratozoospermia, his spermatozoa show head defects by semen examination, Papanicolaou staining and electron microscope assays. Whole-exome sequencing and Sanger sequencing found the proband carries a homozygous ZCWPW1 variant (c.1064C > T, p. P355L). Immunofluorescence analysis shows a significant decrease in ZCWPW1 expression in the proband's sperm. By exogenous expression with ZCWPW1 mutant plasmid in vitro, the obvious declined expression of ZCWPW1 with the mutation is validated in HEK293T. After being treated by hydroxyurea, MUT-ZCWPW1 transfected cells and empty vector transfected cells have a higher level of γ-H2AX, increased tail DNA and reduced H3K9ac level than WT-ZCWPW1 transfected cells. Furthermore, the Sperm Chromatin Dispersion assay revealed the proband's spermatozoa have high DNA fragmentation. CONCLUSIONS: It is the first report that a novel homozygous missense mutation in ZCWPW1 caused human male infertility with sperm head defects and high DNA fragmentation. This finding enriches the gene variant spectrum and etiology of oligoasthenoteratozoospermia.

Enhancing Integrity and Economic Efficiency Through Effective Details Management of Operating Room Devices.

Objective: This study aims to assess the impact of details management on the handling of instruments in the operating room, comprehensively evaluating its impact on device intactness, economic efficiency, overall care quality, and physician satisfaction. Methods: We analyzed 1050 procedural packs used in our hospital from March to December 2019. The control group included 525 procedural packs with conventional management (March-August 2019), while the experimental group had 525 instrument packs with details management. Outcome measures included operating room device use, surgical care quality, and device tracking outcome. Results: Details management showed significantly higher device intactness (97.73%), a marked decrease in device preparation errors (0.00%), and more efficient device checking time (1.13±0.41) compared to conventional management (84.09%, 11.36%, 2.85±1.03) (P < .05). The experimental group had higher scores in intraoperative nursing ability, nursing operating specification, nursing staff professionalism, and device care quality (9.08±0.31, 9.23±0.32, 9.17±0.55, 97.81±0.96) compared to the control group (8.11±0.67, 7.98±0.98, 8.35±0.69, 75.25±1.87) (P < .05). Details management was associated with higher economic efficiency and lower incidences of device loss and mix-up compared to conventional management (P < .05). Conclusions: Implementing details management in instrument handling positively affects device intactness, economic efficiency, overall care quality, and physician satisfaction. It enhances device intactness, reduces device checking time, improves economic efficiency and overall care quality, and increases physician satisfaction. The findings provide insights into the benefits of a detailed instrument management approach in a hospital setting.

Characterizing the temporal dynamics of intrinsic brain activities in depressed adolescents with prior suicide attempts.

Converging evidence has revealed disturbances in the corticostriatolimic system are associated with suicidal behaviors in adults with major depressive disorder. However, the neurobiological mechanism that confers suicidal vulnerability in depressed adolescents is largely unknown. A total of 86 depressed adolescents with and without prior suicide attempts (SA) and 47 healthy controls underwent resting-state functional imaging (R-fMRI) scans. The dynamic amplitude of low-frequency fluctuations (dALFF) was measured using sliding window approach. We identified SA-related alterations in dALFF variability primarily in the left middle temporal gyrus, inferior frontal gyrus, middle frontal gyrus (MFG), superior frontal gyrus (SFG), right SFG, supplementary motor area (SMA) and insula in depressed adolescents. Notably, dALFF variability in the left MFG and SMA was higher in depressed adolescents with recurrent suicide attempts than in those with a single suicide attempt. Moreover, dALFF variability was capable of generating better diagnostic and prediction models for suicidality than static ALFF. Our findings suggest that alterations in brain dynamics in regions involved in emotional processing, decision-making and response inhibition are associated with an increased risk of suicidal behaviors in depressed adolescents. Furthermore, dALFF variability could serve as a sensitive biomarker for revealing the neurobiological mechanisms underlying suicidal vulnerability.

A novel laser resection approach: efficacy of rotatable bi-channel en bloc resection of bladder tumor in a pilot in-vivo study.

En bloc resection of bladder tumor (ERBT) involves removing bladder tumors and their base. Laser resection has been used to reduce complications including bleeding and obturator nerve reflex (ONR). We developed a novel approach (rotatable bi-channel en bloc resection of bladder tumor (RBC-ERBT)) and assessed its efficacy in a pilot in-vivo study to enhance laser ERBT's applicability in challenging bladder regions. In the laser RBC-ERBT procedure, lesions were excised by inserting a holmium laser through the rotating external working channel, while forceps were inserted through the internal working channel provided traction on the tissue. Fifteen laser RBC-ERBT procedures were performed in five different bladder areas of three live pigs. The technical success rate (TSR), procedure time, lesion size, occurrence of complications (bleeding, perforation, ONR), and detrusor muscle (DM) presence rate and DM thickness were evaluated. All 15 procedures were performed with a 100% TSR. The resections were successful in all bladder regions (posterior, left, right and anterior walls and dome). Median procedure time was 20 min. The resected specimen size was 10 mm × 7 mm to 17 mm × 13 mm. Mild bleeding occurred in two procedures (13.3%) but was effectively managed. No incidents of ONR or perforation were observed. Histological examination confirmed presence of DM in all specimens with a median DM thickness of 1.26 mm. Our pilot in-vivo study suggested the feasibility and effectiveness of laser RBC-ERBT for bladder tumors in various locations. This technique offers effective traction, improved visualization, and enhanced laser accessibility. Further studies are required to validate its effectiveness in humans.

Role of type VI secretion system protein TssJ-3 in virulence and intracellular survival of Burkholderia pseudomallei.

TssJ-3 is an outer-membrane lipoprotein and is one of the key components of the type VI secretion system in Burkholderia pseudomallei. TssJ translocates effector proteins to target cells to induce innate immune response in the host. However, the tssJ gene has not been identified in B. pseudomallei and its function in this bacterium has not yet been characterized. tssJ-3 knockout and tssJ-3-complemented B. pseudomallei strains were constructed to determine the effects of tssJ-3 on bacterial growth, biofilm formation, flagellum synthesis, motility, host cell infection, and gene expression in B. pseudomallei. We found that the ΔtssJ-3 mutant strain of B. pseudomallei showed significantly suppressed biofilm formation, flagellum synthesis, bacterial growth, motility, and bacterial invasion into host cells (A549 cells). Furthermore, the ΔtssJ-3 mutation downregulated multiple key genes, including biofilm and flagellum-related genes in B. pseudomallei and induced interleukin-8 gene expression in host cells. These results suggest that tssJ-3, an important gene controlling TssJ-3 protein expression, has regulatory effects on biofilm formation and flagellum synthesis in B. pseudomallei. In addition, B. pseudomallei-derived tssJ-3 contributes to cell infiltration and intracellular replication. This study provides a molecular basis of tssJ-3 for developing therapeutic strategies against B. pseudomallei infections.

Nickel chloride complexes with substituted 4'-phenyl-2',2':6',2″-terpyridine ligands: synthesis, characterization, anti-proliferation activity and biomolecule interactions.

A series of Ni(II) sandwich-like coordinated compounds were synthesized by the reaction of nickel dichloride and ten 4'-(4-substituent phenyl)-2',2':6',2″-terpyridine ligands, and their structures were confirmed by elemental analysis, FT-IR, ESI-MS, solid state ultraviolet spectroscopy and X-ray single crystal diffraction analysis. Three human cancer cell lines and a normal human cell line were used for anti-proliferation potential study: human lung cancer cell line (A549), human esophageal cancer cell line (Eca-109), human liver cancer cells (Bel-7402) and normal human liver cells (HL-7702). The results show that these nickel complexes possess good inhibitory effects on the cancer cells, outperforming the commonly used clinical chemotherapy drug cisplatin. Especially, complexes 3 (-methoxyl) and 7 (-fluoro) have strong inhibitory ability against Eca-109 cell line with IC50 values of 0.223 µM and 0.335 µM, complexes 4 and 6 showed certain cell selectivity, and complex 6 can inhibit cancer cells and slightly poison normal cells when the concentration was controlled. The ability of these complexes binding to CT-DNA was studied by UV titration and CD spectroscopy, and CD spectroscopy was also used to study the secondary structural change of BSA under the action of the complexes. The binding of these complexes with DNA, DNA-Topo I and bovine serum protein has been simulated by molecular docking software, and the docking results and optimal binding conformation data showed that they interacted with DNA in the mode of embedded binding, which is consistent with the experimental results. These complexes are more inclined to move to the cleavage site when docking with DNA-Topo I, so as to play a role of enzyme cleavage, while BSA promotes the action of the complexes by binding to effective binding sites.

Massage therapy significantly improves cancer-related fatigue in cancer patients: a meta-analysis of randomized controlled trials.

PURPOSE: This study was designed to investigate the effectiveness and safety of massage therapy in cancer-related fatigue (CRF) and to provide a reference for the future management of CRF. METHODS: Eight databases (PubMed, Embase, Cochrane Library, CINAHL, Sinomed, Chinese Scientific Journal database (VIP), Wanfang, and China National Knowledge Infrastructure (CNKI)) were systematically reviewed from inception to May 2022 for randomized controlled trials. Two reviewers critically and independently assessed the risk of bias using Cochrane Collaboration criteria and extracted correlated data using the designed form. The meta-analysis was performed using RevMan 5.3 to calculate the pooled effect sizes and 95% confidence intervals (CIs). Sensitivity analysis was performed to find the source of the heterogeneity. Publication bias was assessed via funnel plot analysis and the Egger test. RESULT: A total of 11 qualified studies that included 789 patients (massage therapy group: 389; control group: 400) were included in the meta-analysis. Massage therapy had a marked effect on fatigue in cancer patients [standardized mean difference (SMD) = - 1.69, 95% CI (- 2.46, - 0.93), P < 0.01], especially in breast cancer [SMD = - 1.62, 95% CI (- 2.18, - 1.05), P < 0.01]. Reflexology [SMD = - 2.71, 95% CI (- 4.65, - 0.77), P < 0.01] and Chinese massage [SMD = - 1.14, 95% CI (- 1.95, - 0.33), P < 0.01] can have a more significant effect on fatigue. Massage time is 20 to 40 min [SMD = - 2.39, 95% CI (- 4.13, - 0.66), P < 0.01], twice a week [SMD = - 3.46, 95% CI (- 5.47, - 1.45), P < 0.01] for 3-5 weeks [SMD = - 2.36, 95% CI (- 3.53, - 1.19), P < 0.01], which is more effective in relieving fatigue in cancer patients. Five studies described the occurrence of adverse events and only two studies had adverse events. CONCLUSION: Massage therapy can be effective in relieving fatigue in cancer patients. Current evidence suggests that reflexology is the most effective approach to relieve fatigue, particularly in the breast cancer patients. The optimal intervention frequency and cycle for massage therapy is twice a week for 3-5 weeks, and the optimal duration is 20-40 min.

Association of anhedonia and suicidal ideation in patients with treatment-refractory depression after intravenous ketamine infusions.

OBJECTIVES: Accumulating evidence suggests that the effects of ketamine administered intravenously at subanaesthetic doses on both anhedonic symptoms and suicidal ideation occur independently of depressive symptoms in major depressive disorder (MDD) and bipolar disorder (BD). This study sought to determine the relationship between anhedonia and suicidal ideation after serial ketamine infusions. METHODS: A total of 79 subjects with either treatment-refractory MDD (n = 60) or BD (n = 19) were included in a clinical ketamine study. The Montgomery-Åsberg Depression Rating Scale (MADRS) anhedonia factor and the first five items of the Scale for Suicidal Ideations (SSI-Part I) were used to assess anhedonia symptoms and suicidal ideation, respectively. RESULTS: At baseline, anhedonia, as measured by the MADRS, was not significantly associated with suicidal ideation or specific suicide-related ideation as measured by SSI-Part I (all p's > 0.05). Only the 'wish to die' and 'desire to make a suicide attempt' items were positively associated with anhedonia at two weeks after the sixth ketamine infusion, which was independent of the reductions in depressive symptoms (all p's < 0.05). CONCLUSION: Anhedonia as measured by the MADRS appeared to not be positively related to suicidal ideation after serial ketamine infusions.KEY POINTSSerial ketamine (0.5 mg/kg) infusions have shown quick and dramatic antisuicidal and antianhedonic effects in patients with depression.The association between anhedonia and suicidal ideation after serial ketamine infusions is unclear.Anhedonia appeared to not be positively related to suicidal ideation after serial ketamine infusions.

Magnetic Resonance Imaging Guided Prostate Biopsy in Patients with ≥ One Negative Systematic Transrectal Ultrasound-Guided Biopsy: A Systemic Review and Meta-Analysis.

The present study aimed to compare prostate cancer (PCa) and clinically significant PCa (csPCa) detection sensitivity between magnetic resonance imaging guided-biopsy (MRI-GB) and transrectal ultrasound-guided biopsy (TRUS-GB) in patients with ≥ 1 negative TRUS-GB, and to explore the additive value of TRUS-GB to MRI-GB. The meta-analysis of 18 studies demonstrated that MRI-GB had a similar sensitivity for PCa detection but a higher sensitivity for csPCa than TRUS-GB. In conclusion, there was limited value in combining TRUS-GB with MRI-GB compared with MRI-GB alone for csPCa detection in patients with one or more negative TRUS-GBs that were suspicious of having PCa.

The efficacy and safety of esketamine in the treatment of major depressive disorder with suicidal ideation: study protocol for a randomized controlled trial.

BACKGROUND: Major depressive disorder (MDD) is a high risk factor for suicide, with up to 20% of MDD patients attempting suicide during their lifetime. Current treatments for MDD are slow onset of action, low efficiency, and the inability to control suicidal behaviors quickly and effectively. Intravenous ketamine has been shown to have a rapid but transient antidepressant effect, but there is still lack evidence on the efficacy and safety of intravenous esketamine in reducing suicidal ideation and depressive symptoms in MDD patients with suicidal ideation. We designed a study to investigate the effect of short-term repeated intravenous infusion of esketamine three times in MDD patients with suicidal ideation. METHODS: This study features a randomized, double-blind, placebo-controlled trial (RCT) comparing short-term repeated intravenous infusions of esketamine with placebo as a supplement to conventional antidepressants with an intervention period of 6 days and one infusion every other day, followed by 4 weeks of follow-up. These methods support the examination of the efficacy, safety, tolerability, and mechanism of action of short-term repeated intravenous infusions of esketamine in MDD patients with suicidal ideation. DISCUSSION: This is the first RCT to explore the efficacy and safety of short-term repeated infusion of esketamine on suicidal ideation and depressive symptoms in MDD patients with suicidal ideation. If proven effective and tolerated, it will provide evidence for rapid and effective treatment of suicidal ideation and depressive symptoms in MDD individuals with suicidal ideation. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2000041232 . Registered 22 December 2020.

Elevated serum levels of TNF-α, IL-6, and IL-18 in chronic methamphetamine users.

OBJECTIVE: Chronic methamphetamine use causes aberrant changes in cytokines. Our aim was to analyze the serum levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-18 in chronic methamphetamine users. Associations between cytokines levels with the demographic properties, methamphetamine use properties, and psychiatric symptoms in chronic methamphetamine users were also evaluated. METHODS: Seventy-eight chronic methamphetamine users who did not continue methamphetamine exposure since hospitalization and 64 healthy controls were enrolled. Serum levels of TNF-α, IL-6, and IL-18 were detected using an enzyme-linked immunosorbent assay. Psychopathological symptoms of chronic methamphetamine users were evaluated by the Positive and Negative Syndrome Scale, Beck Depression Inventory (BDI), and Beck Anxiety Inventory. RESULTS: Serum levels of TNF-α, IL-6, and IL-18 were significantly increased in methamphetamine users who did not continue methamphetamine exposure since hospital admission (average days since last methamphetamine use = 39.06 ± 7.48) when compared to those in controls. Serum IL-6 levels showed significant positive associations with BDI score and current frequency of methamphetamine use in chronic methamphetamine users. CONCLUSIONS: Our results suggest that increased TNF-α, IL-6, and IL-18 levels may have an important role in chronic methamphetamine use-associated psychopathological symptoms.

Plasma inflammatory cytokines and treatment-resistant depression with comorbid pain: improvement by ketamine.

BACKGROUND: Treatment-resistant depression (TRD) and pain frequently coexist clinically. Ketamine has analgesic and antidepressant effects, but few studies have evaluated individual differences in antidepressant outcomes to repeated ketamine in TRD patients with comorbid pain. Our aims were to determine the difference in ketamine's antidepressant effects in TRD patients with or without pain and then to examine whether inflammatory cytokines might contribute to ketamine's effect. METHODS: Sixty-six patients with TRD received six infusions of ketamine. Plasma levels of 19 inflammatory cytokines were assessed at baseline and post-infusion (day 13 and day 26) using the Luminex assay. Plasma inflammatory cytokines of sixty healthy controls (HCs) were also examined. RESULTS: TRD patients with pain had a higher antidepressant response rate (χ2 = 4.062, P = 0.044) and remission rate (χ2 = 4.062, P = 0.044) than patients without pain. Before ketamine treatment, GM-CSF and IL-6 levels were higher in the pain group than in the non-pain and HC groups. In the pain group, levels of TNF-α and IL-6 at day 13 and GM-CSF, fractalkine, IFN-γ, IL-10, MIP-3α, IL-12P70, IL-17α, IL-1ß, IL-2, IL-4, IL-23, IL-5, IL-6, IL-7, MIP-1ß, and TNF-α at day 26 were lower than those at baseline; in the non-pain group, TNF-α levels at day 13 and day 26 were lower than those at baseline. In the pain group, the changes of IL-6 were associated with improvement in pain intensity (ß = 0.333, P = 0.001) and depressive symptoms (ß = 0.478, P = 0.005) at day 13. Path analysis showed the direct (ß = 2.995, P = 0.028) and indirect (ß = 0.867, P = 0.042) effects of changes of IL-6 on improvement in depressive symptoms both were statistically significant. CONCLUSION: This study suggested that an elevated inflammatory response plays a critical role in individual differences in TRD patients with or without pain. Ketamine showed great antidepressant and analgesic effects in TRD patients with pain, which may be related to its effects on modulating inflammation. TRIAL REGISTRATION: ChiCTR , ChiCTR-OOC-17012239. Registered on 26 May 2017.

Working memory associated with anti-suicidal ideation effect of repeated-dose intravenous ketamine in depressed patients.

Suicide is a tremendous threat to global public health, and a large number of people who committed suicide suffered the pain of mental diseases, especially major depressive disorder (MDD). Previous study showed that ketamine could reduce suicidal ideation (SI), potentially by improving the impaired working memory (WM). The objective of current study was to illuminate the relationship between WM and SI in MDD with repeated ketamine treatment. MDD patients with SI (n = 59) and without SI (n = 37) completed six intravenous infusions of ketamine (0.5 mg/kg over 40 min) over 12 days (Day 1, 3, 5, 8, 10 and 12). The severity of depressive symptoms, SI and WM were assessed at baseline, day 13 and day 26. We found that WM was significantly improved after 6 ketamine infusions (F = 161.284, p = 0.009) in a linear mixed model. Correlation analysis showed that the improvement of depressive symptom was significantly associated with WM at baseline (r = - 0.265, p = 0.042) and the reduction in SSI-part I was related to the change of WM (r = 0.276, p = 0.034) in the MDD patients with SI. Furthermore, Logistic regression analysis showed that improvement in WM might predict the anti-SI response of ketamine. Our findings suggest that the improvement of working memory may partly account for the anti-SI effect of ketamine, and intervention of improving working memory function may be capable of reducing suicidal ideation.

Study on the substitution effects of zinc benzoate terpyridine complexes on photoluminescence, antiproliferative potential and DNA binding properties.

Six zinc(II) complexes, [Zn(OCOPh)2LR] (R = 1, 2, 3, 4, 5, 6) were synthesized by the reaction of zinc benzoate and six para-substituted 4-phenyl-terpyridine complexes and their structures were confirmed by elemental analysis, FT-IR, 1H NMR and X-ray single crystal diffraction analysis. Their photoluminescent properties in solid and in solutions of DMSO were studied. Three human cancer cell lines were used for antiproliferative potential: human lung cancer cell line (A549), human esophageal cancer cell line (Eca-109) and human breast cancer cell line (MCF-7). The results have shown that these zinc complexes have good inhibitory effects on cancer cells, which are better than that of the commonly used clinical drug cisplatin. The ability of the complexes to binding to CT-DNA was studied by UV spectroscopy and fluorescence titration, while the interaction between the complexes and CT-DNA, AT6, GC6 short-chain DNA sequences and G-quadruplex were analyzed by circular dichroism (CD). It is found that these complexes can bind to DNA, and the binding mode is mainly intercalator. The docking of the complexes with the DNA fragment was simulated using molecular docking software. All the results clearly display that the substituents at these ligands of the complexes have the substitution effects on the properties of photoluminescence, antiproliferative potential and DNA binding study.

GRIN2B Gene Polymorphism in Chronic Ketamine Users.

BACKGROUND AND OBJECTIVES: We examined the allelic variants of N-methyl- d-aspartate receptor 2B (GRIN2B) and analyzed the associations between GRIN2B gene polymorphism with ketamine use conditions and psychopathological symptoms in chronic ketamine users. METHODS: A total of 231 subjects were recruited. Four single nucleotide polymorphisms of GRIN2B, rs1805502, rs7301328, rs890, and rs1806201 were examined in 151 male chronic ketamine users and 80 controls. Psychopathological symptoms in chronic ketamine users were evaluated using the Positive and Negative Syndrome Scale, the Beck Depression Inventory, and the Beck Anxiety Inventory. RESULTS: The genotype CC of rs1806201 had a lower frequency in ketamine users than that in control subjects (χ2 = 8.167, P = .004) and the T allele frequency of rs1806201 in ketamine users was higher than that in the control subjects (P = .009, odds ratio = 2.019 [1.196-3.410]). Ketamine users of genotype TT and CC of rs1806201 had an earlier onset of ketamine use than subjects of genotype TC (P = .038, P = .049, respectively). The dose of ketamine consumption per day of use was higher in genotype GG of rs7301328 than that in those with CG in ketamine users (P = .026). There were no significant differences of the severity of psychopathologic symptoms among different genotypes tested. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: GRIN2B gene polymorphism may play a role in ketamine abuse. (Am J Addict 2020;29:105-110).

TGF-ß Signaling Induces the Expression of OPN in Blood Vessel Endothelial Cells.

BACKGROUND: The mechanism of blood vessel formation and degeneration still remains unclear. Transforming growth factor-ß1 (TGF-ß1) signaling is a critical pathway in this progression and can induce multiple biological effects. Osteopontin (OPN) is involved in mineral metabolism and the inflammatory response associated with vascular calcification. METHODS: To identify the relationship between TGF-ß signaling pathway and OPN, we stimulated human vascular endothelial cells (HVECs) and human aortic endothelial cells (HAECs) using various concentration of TGF-ß1 in vitro. RESULTS: As assessed by flow cytometry and western blots, apoptosis levels were significantly increased with TGF-ß1 treatment. We also demonstrated that OPN increased in vitro with TGF-ß signaling by western blot and quantitative real time polymerase chain reaction (qRT-PCR) analyses. The inhibitory phosphorylation of endothelial nitric-oxide synthase (eNOS) (Thr495) was also up-regulated by TGF-ß signaling. Meanwhile, the anti-inflammatory factor Nrf2 and the activating phosphorylation of eNOS (Ser1177) were down-regulated. CONCLUSIONS: Taken together, our findings demonstrate that TGF-ß signaling can induce the expression of OPN, which may play an important role in the dysfunction of the vascular wall.

Antidepressant effect of repeated ketamine administration on kynurenine pathway metabolites in patients with unipolar and bipolar depression.

Ketamine has rapid antidepressant effects on treatment-resistant depression, but the biological mechanism underpinning this effect is less clear. Our aims were to examine whether kynurenine pathway metabolites were altered by six infusions of ketamine and whether these biological factors could act as potential biomarkers to predict ketamine's antidepressant effects. Six intravenous infusions of ketamine (0.5 mg/kg) were administered to 84 patients with unipolar and bipolar depression over a 12-d period. Symptom severity and response were assessed using the Montgomery-Asberg Scale (MADRS), and blood samples were collected at baseline and 24 h following the first infusion and at 24 h and 14 d after the sixth infusion (24 h, 13 d and 26 d). Blood samples from sixty healthy controls were collected for comparison with samples from the patients. Serum concentrations of tryptophan (TRP), kynurenine (KYN) and kynurenic acid (KYNA) were measured by the liquid chromatography-tandem mass spectrometry method. At baseline, serum levels of TRP and KYNA and the KYNA/KYN ratio were lower and the KYN/TRP ratio was greater in depressed patients than in healthy controls. Overall, fifty (59.5%) patients responded to ketamine at 13 d. Ketamine responders had a greater KYNA level and KYNA/KYN ratio than nonresponders at 24 h and 13 d (all P < 0.05). Elevations in the KYNA levels and KYNA/KYN ratio at 24 h were significantly associated with reductions in MADRS scores at 24 h, 13 d and 26 d in the linear regression analysis (all P < 0.05). Our results showed a possible involvement of the kynurenine pathway in the rapid antidepressant effect of ketamine. Early changes in serum KYNA levels and the KYNA/KYN ratio could be potential predictors of antidepressanteffects of repeated ketamine administration.

Study on the Photoluminescent and Thermal Properties of Zinc Complexes with a N6O4 Macrocyclic Ligand.

Reactions between a N6O4 macrocyclic ligand (L¹) and several Zn(II) salts (trifluoromethane sulfonate, p-toluenesulfonate, acetate, benzoate, o-, m- or p-hydroxybenzoate) led to the formation of seven complexes, [Zn2L¹ (DMSO)4](OSO2CF3)4 (1), [Zn2(p-OSO2PhCH3)4L¹] (2), [Zn2(OCOCH3)4L¹] (3), [Zn2(OCOPh)4L¹] (4), [Zn2(o-OCOPhOH)4L¹] (5), [Zn2(m-OCOPhOH)4 L¹] (6) and [Zn2(p-OCOPhOH)4 L¹] (7), which were characterized by elemental analysis, ¹H-NMR, 13C-NMR, IR, fluorescence spectroscopies and single crystal X-ray diffraction. In 1, the Zn atom is pentacoordinated with a N3O2 irregular trigonal bipyramidal coordination environment, like the geometries in compounds 3⁻7, whereas in structure 2 the metal atom is envisaged as possessing a distorted N3O3 octahedronal environment. All the compounds show interesting photoluminescent properties in solid states and solutions in DMF and DMSO, which are reported along with their TG-DTA thermal decomposition processes, UV-vis absorption spectroscopy and fluorescence quantum yields in DMF and DMSO.