Challenges and opportunities in animal models of psoriatic arthritis.

OBJECTIVE: To review the preparation, characteristics and research progress of different PsA animal models. METHODS: Computerized searches were conducted in CNKI, PubMed and other databases to classify and discuss the relevant studies on PsA animal models. The search keywords were "PsA and animal model(s), PsA and animal(s), PsA and mouse, PsA and mice, PsA and rat(s), PsA and rabbit(s), PsA and dog(s)" RESULTS: The experimental animals currently used to study PsA are mainly rodents, including mice and rats. According to the different methods of preparing the models, the retrieved animal models were classified into spontaneous or genetic mutation, transgenic and induced animal models. These PsA animal models involve multiple pathogenesis, some experimental animals' lesions appear in a short and comprehensive cycle, some have a high success rate in molding, and some are complex and less reproducibility. This article summarizes the preparation methods, advantages and disadvantages of different models. CONCLUSIONS: The animal models of PsA aim to mimic the clinicopathological alterations of PsA patients through gene mutation, transgenesis or targeted proinflammatory factor and to reveal new pathogenic pathways and therapeutic targets by exploring the pathological features and clinical manifestations of the disease. This work will have very far-reaching implications for the in-depth understanding of PsA and the development of new drugs.

Management of vaginal laxity through bilateral wall tightening without mucosal excision.

BACKGROUND: Vaginal tightening or vaginoplasty has been gaining popularity, while validated methods of evaluation and treatment are still lacking. Herein, we describe a bilateral wall tightening technique for vaginal laxity and evaluate the feasibility of this method. METHODS: From April 2020 to September 2021, 25 women with vaginal laxity underwent vaginal tightening, and 22 women were included in this retrospective observational study. The inclusion criteria were as follows: participants with at least one delivery and reported vaginal laxity, but without a history of underlying diseases. Vaginal pressure tests and questionnaires were used to evaluate vaginal laxity and sexual quality before and 6 months after the surgery. RESULTS: The study included 22 women (aged 29-46 years), and the follow-up period was 14.1 ± 3.3 months. The score based on the vaginal laxity questionnaire was improved as a result of surgery (preoperative median: 2.00, interquartile range [IQR]: 1.00-2.00; postoperative median: 5.00, IQR: 5.00-6.25, p < 0.001). The vaginal pressure increased from 2.3 ± 1.8 mm/Hg to 21.4 ± 3.7 mm/Hg. Sexual distress changed from 24.2 ± 8.9-16.1 ± 4.8 after surgery (p < 0.001), and sexual dysfunction with an average score of 20.1 ± 10.6 before surgery improved after the procedure (26.0 ± 10.8, p < 0.001). Women also reported improved scores in desire, arousal, orgasm, and satisfaction. In addition, there were no intraoperative complications or significant events during the follow-up period. CONCLUSIONS: Bilateral vaginal tightening without mucosal excision is a feasible and effective surgical approach for the management of vaginal laxity.

Synovial Macrophages: Past Life, Current Situation, and Application in Inflammatory Arthritis.

Inflammatory arthritis is an inflammatory disease that involves the joints and surrounding tissues. Synovial hyperplasia often presents when joints become inflamed due to immune cell infiltration. Synovial membrane is an important as well as a highly specific component of the joint, and its lesions can lead to degeneration of the joint surface, causing pain and joint disability or affecting the patients' quality of life in severe cases. Synovial macrophages (SMs) are one of the cellular components of the synovial membrane, which not only retain the function of macrophages to engulf foreign bodies in the joint cavity, but also interact with synovial fibroblasts (SFs), T cells, B cells, and other inflammatory cells to promote the production of a variety of pro-inflammatory cytokines and chemokines, such as TNF-α, IL-1ß, IL-8, and IL-6, which are involved in the pathogenic process of inflammatory arthritis. SMs from different tissue sources have differently differentiated potentials and functional expressions. This article provides a summary on studies pertaining to SMs in inflammatory arthritis, and explores their role in its treatment, in order to highlight novel treatment modalities for the disease.

GDF11 Alleviates Pathological Myocardial Remodeling in Diabetic Cardiomyopathy Through SIRT1-Dependent Regulation of Oxidative Stress and Apoptosis.

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor ß superfamily that alleviates cardiac hypertrophy, myocardial infarction, and vascular injury by regulating oxidative stress, inflammation, and cell survival. However, the roles and underlying mechanisms of GDF11 in diabetic cardiomyopathy (DCM) remain largely unknown. In this study, we sought to determine whether GDF11 could prevent DCM. After establishing a mouse model of diabetes by administering a high-fat diet and streptozotocin, intramyocardial injection of an adeno-associated virus was used to achieve myocardium-specific GDF11 overexpression. GDF11 remarkably improved cardiac dysfunction and interstitial fibrosis by reducing the levels of reactive oxygen species and protecting against cardiomyocyte loss. Mechanistically, decreased sirtuin 1 (SIRT1) expression and activity were observed in diabetic mice, which was significantly increased after GDF11 overexpression. To further explore how SIRT1 mediates the role of GDF11, the selective inhibitor EX527 was used to block SIRT1 signaling pathway, which abolished the protective effects of GDF11 against DCM. In vitro studies confirmed that GDF11 protected against H9c2 cell injury in high glucose and palmitate by attenuating oxidative injury and apoptosis, and these effects were eliminated by SIRT1 depletion. Our results demonstrate for the first time that GDF11 protects against DCM by regulating SIRT1 signaling pathway.

Effects of dexmedetomidine on post-operative recovery and mental status in patients receiving robotic-assisted thoracic surgery.

BACKGROUND: This study aimed to investigate the effects of dexmedetomidine on the post-operative recovery and mental status in patients receiving robotic-assisted thoracic surgery (RATS). METHODS: One hundred patients who received selective RATS under general anesthesia were recruited and assigned into control group (C) and dexmedetomidine group (D). The anesthesia induction and maintenance were consistent between groups. Midazolam, sufentanil, propofol and rocuronium were intravenously injected for anesthesia induction, followed by mechanical ventilation after endotracheal intubation. Sevoflurane inhalation at a minimum alveolar concentration (MAC) of 0.5 was administered, propofol and remifentanil were intravenously injected to maintain the bispectral index (BIS) at 40-60, and rocuronium was intravenously injected once every 30 min. In the D group, dexmedetomidine was intravenously injected after endotracheal intubation, and then it was injected before the end of surgery. In the C group, normal saline of equal volume was injected. The hemodynamic parameters, blood loss, urine volume, time of surgery, time of anesthesia, total dose of propofol, time of thoracic tube indwelling, hospital stay and pulmonary complications were recorded; blood gas analysis was performed after extubation; the QoR-15 and mini-mental state examination (MMSE) questionnaires were employed for the assessment of mental status at 1 and 3 days after surgery. RESULTS: The mean arterial pressure (MAP), heart rate (HR) and brain oxygenation were similar between groups at different time points (P>0.05). There were no significant differences in the operation time, time of anesthesia and intra-operative urine volume between groups. As compared to the C group, the blood loss and dose of propofol reduced significantly (P<0.05). After extubation, the respiratory frequency reduced and PaO2 increased markedly (P<0.05). After surgery, the time of thoracic tube indwelling and hospital stay reduced dramatically in the D group as compared to the C group (P<0.05). The QoR-15 score and MMSE score in the D group were markedly higher than in the C group (P<0.05). CONCLUSIONS: Dexmedetomidine can improve the post-operative recovery and mental status after RATS.

The source of ACE during scar formation is from both bone marrow and skin tissue.

Angiotensin-converting enzyme (ACE) has been found in the pathogenesis of various fibrosis diseases, and ACE inhibitor (ACEI) may affect wound healing and cutaneous fibrosis. However, there is no scientific evidence as to where the ACE is produced during scar formation. Whether it is from the cutaneous tissue or the bone marrow, or both remains unknown. In this study, we investigated the source of ACE using bone marrow transplantation in genetically modified mice, analyzed the inflammatory milieu and some growth factors in the middle of the wound healing period (4 d after the wound was induced). After having deleted the ACE from bone marrow or skin tissue, the wound/scar width in the low-ACE groups were narrower than those in wild-type (WT) controls. Loosely arranged collagen deposition and reduced vessel density were also detected in ACE-deficient mice. Lower ACE levels during scar formation were also accompanied by lower levels of TGF-ß1. In the middle of the wound healing period, ACE levels affected the inflammatory cells significantly. In the mice with a deficiency in ACE, the expression of TGF-ß1 and TNF-α decreased, but not that of IL-4. Our findings indicate that both bone marrow and skin tissue release ACE during scar formation. Deleting either of them can affect the inflammatory cells and growth factors and reduce the expression of TGF-ß1, resulting in a decreased level of scarring.-Fang, Q.-Q., Wang, X.-F., Zhao, W.-Y., Chen, C.-Y., Zhang, M.-X., Shi, B.-H., Zhang, L.-Y., Tan, W.-Q. The source of ACE during scar formation is from both bone marrow and skin tissue.

Madelung's Disease: Lipectomy or Liposuction?

BACKGROUND: Madelung's disease is a rare lipid metabolic disorder characterized by diffuse, uncapsulated lipomas in the neck, shoulder, and other areas. It mainly affects middle-aged men and is related to alcohol abuse, and the cause is not clear. Surgical treatments include lipectomy and liposuction. METHODS: This systematic review analyzed the treatment of Madelung's disease described in 52 articles including complete patient details, published between 2000 and 2015, and retrieved from the Web of Science, PubMed, Medline, and Embase. RESULTS: Lipectomy was performed in most cases and achieved more complete removal and better control of iatrogenic lesions of nearby structures than liposuction. Liposuction achieved good cosmetic results and is simpler and less invasive than lipectomy, but clinical experience is limited. CONCLUSIONS: Both lipectomy and liposuction have advantages and drawbacks. Surgeons should base the choice of optimal treatment on patient characteristics. Novel surgical techniques and etiologically targeted treatments hold promise as future therapies.

Percutaneous intraductal radiofrequency ablation for treatment of biliary stent occlusion: A preliminary result.

AIM: To assess the feasibility and effectiveness of a novel application of percutaneous intraductal radiofrequency (RF) for the treatment of biliary stent obstruction. METHODS: We specifically report a retrospective study presenting the results of percutaneous intraductal RF in patients with biliary stent occlusion. A total of 43 cases involving biliary stent obstruction were treated by placing an EndoHPB catheter and percutaneous intraductal RF was performed to clean stents. The stent patency was evaluated by cholangiography and follow-up by contrast enhanced computed tomography or ultrasound after the removal of the drainage catheter. RESULTS: Following the procedures, of the 43 patients, 40 survived and 3 died with a median survival of 80.5 (range: 30-243) d. One patient was lost to follow-up. One patient had the stent patent at the time of last follow-up. Two patients with stent blockage at 35 d and 44 d after procedure underwent percutaneous transhepatic drain insertion only. The levels of bilirubin before and after the procedure were 128 ± 65 µmol/L and 63 ± 29 µmol/L, respectively. There were no related complications (haemorrhage, bile duct perforation, bile leak or pancreatitis) and all patients' stent patency was confirmed by cholangiography after the procedure, with a median patency time of 107 (range: 12-180) d. CONCLUSION: This preliminary clinical study demonstrated that percutaneous intraductal RF is safe and effective for the treatment of biliary stent obstruction, increasing the duration of stent patency, although randomized controlled trials are needed to confirm the effectiveness of this approach.

Effectiveness and Complications of Improved Liposuction-Curettage Through Mini-Incisions for the Treatment of Axillary Osmidrosis.

BACKGROUND: Liposuction-curettage (LC) is a popular and effective surgical method for the treatment of axillary bromhidrosis (AB). However, residual malodour and skin necrosis often appear after this type of surgery. We investigated the efficacy and complications of 4 methods of LC. METHODS: A total of 280 patients with AB comprised the study cohort, of which 228 were followed up. We carried out 4 methods of modified tumescent LC through mini-incisions and provided a questionnaire for evaluation of surgical outcome. Evaluations were malodour elimination, scarring, reduced growth of hair, and complications. Mean follow-up was 15 months. RESULTS: The study involved 449 axillae. In patients with LC in the final phase of improvement (programmed and well-organized LC, skin pinching to wrap up the cannula, LC to the skin around 2 surgical incisions, and cotton balls packed in gauze and an elastic set for post-operative management), excellent elimination of malodor was observed in 141 (89.81%) of 157 axillae. Only 4 (2.55%) cases encountered a small area of skin necrosis, and 28 (17.83%) had local damage to the epidermis. CONCLUSION: These data suggest that LC with a final phase of improvement through mini-incisions is effective for AB treatment.

HISTORIQUE: La liposuccion-curetage (LC) est un mode opératoire efficace et populaire pour traiter la bromidrose axillaire (BA). Cependant, de mauvaises odeurs résiduelles et une nécrose cutanée se produisent souvent après ce type d'opération. Les auteurs ont examiné l'efficacité et les complications de quatre types de LC. MÉTHODOLOGIE: Au total, 280 patients ayant une BA ont formé la cohorte de l'étude, dont 228 ont fait l'objet d'un suivi. Les auteurs ont effectué quatre types de LC tumescente modifiée par mini-incisions et ont remis un questionnaire d'évaluation des résultats de l'opération. Les points évalués étaient l'élimination des mauvaises odeurs, la cicatrice, la réduction de la pilosité et les complications. Le suivi moyen était de 15 mois. RÉSULTATS: L'étude portait sur 449 aisselles. Chez les patients ayant subi une LC qui en étaient à la dernière phase d'amélioration (LC programmée et bien organisée, pincement de la peau pour installer la canule, LC jusqu'à la peau par deux incisions chirurgicales, tampons d'ouate emballés dans de la gaze et bandage élastique pour la prise en charge postopératoire), les auteurs ont observé une excellente élimination des mauvaises odeurs dans 141 aisselles sur 157 (89,81%). Seulement quatre cas (2,55%) ont présenté une petite région de nécrose cutanée et 28 (17,83%), une atteinte locale de l'épiderme. CONCLUSION: Selon ces données, la LC accompagnée d'une phase finale d'amélioration par mini-incisions est efficace pour traiter la BA.

[Plasma mannan?binding lectin and MBL?associated serine protease 2 in patients with hepatocellular carcinoma].

OBJECTIVE: To detect the plasma levels of mannan?binding lectin (MBL) and MBL?associated serine protease?2 (MASP-2) in patients with hepatocellular carcinoma (HCC) and explore their role in the tumorigenesis and progression of HCC. METHODS: The plasma levels of MBL and MASP?2 were detected by enzyme?linked immunosorbent assay in 64 HCC patients and 30 healthy control subjects. The correlation of MBL and MASP?2 with the clinical parameters of HCC patients were analyzed. RESULTS: The plasma levels of MBL (P=0.014) and MASP?2 (P=0.002) were significantly higher in HCC patients than in the healthy controls, but the MBL?to?MASP?2 ratio did not differ significantly between the two groups. In HCC patients, plasma MBL level was positively correlated with vascular invasion (r=0.253, P=0.047) and total bilirubin level (r=0.283, P=0.024). The plasma level of MASP?2 was positively correlated with TNM stage (r=0.276, P=0.027) and negatively correlated with plasma albumin level (r=0.?0.317, P=0.015). ROC curve analysis revealed an area under curve of 0.665 for MBL (P=0.010) and 0.694 for MASP?2 (P=0.003). The sensitivities of MBL and MASP?2 were 50% and 89.1% in the diagnosis of HCC, respectively. CONCLUSION: MBL and MASP?2 are associated with the inflammatory state and disease progression in patients with HCC.

A CE-LIF method based on long wavelength fluorescence labeling for the analysis of thiols in human urine.

A rapid and robust CE method using a long wavelength fluorescent reagent 1,7-dimethyl-3,5-distyryl-8-phenyl-(2-maleimide)difluoroboradiaza-s-indacene as the labeling reagent has been developed for the simultaneous determination of thiols, including glutathione, cysteine, homocysteine, N-acetylcysteine, cysteinylglycine, and penicillamine. The derivatization reaction was carried out in 14 mmol/L pH 8.5 borate buffer at 30°C for 6 min and the labeled thiols derivatives were separated with the running buffer containing 30 mmol/L pH 7.4 phosphate, 30% v/v acetonitrile and 8 mmol/L SDS within 12 min. Detection limits ranged from 0.4 to 2.4 nmol/L. To demonstrate the capability of this method, it was applied to the analysis of thiols in human urine with recoveries of 92.4-105.6%. The derivatization reaction was much faster at milder conditions, and the analysis was rapider. Moreover, with excitation wavelength at long wavelength region, background interference from samples was reduced effectively. The present method seems to be a potential choice for quantifying thiols in human urine.

Mannan-binding lectin at supraphysiological concentrations inhibits differentiation of dendritic cells from human CD14+ monocytes.

Mannan-binding lectin (MBL), a circulating C-type lectin, is an important member of the defense collagen family. It exhibits a high potential for recognizing broad categories of pathogen-associated molecular patterns and initiating complement cascade responses. DCs are well-known specialist antigen-presenting cells that significantly trigger specific T cell-mediated immune responses. In our previous study, it was observed that high concentrations of MBL significantly attenuate LPS-induced maturation of monocyte-derived DCs (MoDCs). In the current study, it was postulated that MBL at similar supraphysiological concentrations would affect early differentiation of MoDCs in some way. CD14(+) monocytes from human peripheral blood mononuclear cells were cultured with granulocyte-macrophage colony-stimulating factor and IL-4 in the presence or absence of physiological (1 µg/mL) and supraphysiological concentrations (20 µg/mL) of MBL protein, respectively. Phenotypic analysis indicated that the differentiated DCs incubated with high concentrations of MBL expressed MHC class II and costimulatory molecules (e.g., CD80 and CD40) more weakly than did control groups. The secretion of IL-10 and IL-6 increased markedly, whereas their mixed lymphocyte reaction-stimulating capacity decreased. Members of the signal transducer and activator of transcription family were also found to be differentially regulated. Thus, beyond the role of MBL as an opsonin, our data reveal a possible inhibitory effect of MBL at high concentrations in monocyte-DC transition, which probably provides one way of regulating adaptive immune responses by strict regulation of DCs, making MBL a better prospect for controlling relevant pathological events such as autoimmune diseases.

Biological effects of low-dose-rate irradiation of pancreatic carcinoma cells in vitro using 125I seeds.

AIM: To determine the mechanism of the radiation-induced biological effects of 125I seeds on pancreatic carcinoma cells in vitro. METHODS: SW1990 and PANC-1 pancreatic cancer cell lines were cultured in DMEM in a suitable environment. Gray's model of iodine-125 (125I) seed irradiation was used. In vitro, exponential phase SW1990, and PANC-1 cells were exposed to 0, 2, 4, 6, and 8 Gy using 125I radioactive seeds, with an initial dose rate of 12.13 cGy/h. A clonogenic survival experiment was performed to observe the ability of the cells to maintain their clonogenic capacity and to form colonies. Cell-cycle and apoptosis analyses were conducted to detect the apoptosis percentage in the SW1990 and PANC-1 cells. DNA synthesis was measured via a tritiated thymidine (3H-TdR) incorporation experiment. After continuous low-dose-rate irradiation with 125I radioactive seeds, the survival fractions at 2 Gy (SF2), percentage apoptosis, and cell cycle phases of the SW1990 and PANC-1 pancreatic cancer cell lines were calculated and compared. RESULTS: The survival fractions of the PANC-1 and SW1990 cells irradiated with 125I seeds decreased exponentially as the dose increased. No significant difference in SF2 was observed between SW1990 and PANC-1 cells (0.766±0.063 vs 0.729±0.045, P<0.05). The 125I seeds induced a higher percentage of apoptosis than that observed in the control in both the SW1990 and PANC-1 cells. The rate of apoptosis increased with increasing radiation dosage. The percentage of apoptosis was slightly higher in the SW1990 cells than in the PANC-1 cells. Dose-dependent G2/M cell-cycle arrest was observed after 125I seed irradiation, with a peak value at 6 Gy. As the dose increased, the percentage of G2/M cell cycle arrest increased in both cell lines, whereas the rate of DNA incorporation decreased. In the 3H-TdR incorporation experiment, the dosimetry results of both the SW1990 and PANC-1 cells decreased as the radiation dose increased, with a minimum at 6 Gy. There were no significant differences in the dosimetry results of the two cell lines when they were exposed to the same dose of radiation. CONCLUSION: The pancreatic cancer cell-killing effects induced by 125I radioactive seeds mainly occurred via apoptosis and G2/M cell cycle arrest.

A new BODIPY-based long-wavelength fluorescent probe for chromatographic analysis of low-molecular-weight thiols.

A new long-wavelength fluorescent probe, 1,7-dimethyl-3,5-distyryl-8-phenyl-(4'-iodoacetamido)difluoroboradiaza-s-indacene (DMDSPAB-I), was designed and synthesized for thiol labeling in high-performance liquid chromatography (HPLC). The excitation and emission wavelengths of DMDSPAB-I are 620 and 630 nm, respectively, with a high fluorescence quantum yield of 0.557, which is advantageous in preventing interference of intrinsic fluorescence from complex biological matrices and enabling high sensitivity HPLC. Based on DMDSPAB-I, a reversed-phase HPLC method was developed for measuring low-molecular-weight thiols including glutathione, cysteine, homocysteine, N-acetylcysteine, cysteinylglycine, and penicillamine. After the specific reaction of DMDSPAB-I with thiols, baseline separation of all six stable derivatives was achieved through isocratic elution on a C18 column within 25 min, with the limits of detection (signal-to-noise ratio = 3) from 0.24 nmol L(-1) for glutathione to 0.72 nmol L(-1) for penicillamine. The proposed method was validated in part by measuring thiols in blood samples from mice, with recoveries of 95.3-104.3%.

Rapid and sensitive determination of free thiols by capillary zone electrophoresis with near-infrared laser-induced fluorescence detection using a new BODIPY-based probe as labeling reagent.

A CZE with near-infrared (NIR) LIF detection method has been developed for the analysis of six low molecular weight thiols including glutathione, homocysteine, cysteine, γ-glutamylcysteine, cysteinylglycine, and N-acetylcysteine. For this purpose, a new NIR fluorescent probe, 1,7-dimethyl-3,5-distyryl-8-phenyl-(4'-iodoacetamido)difluoroboradiaza-s-indacene was utilized as the labeling reagent, whose excitation wavelength matches the commercially available NIR laser line of 635 nm. The optimum procedure included a derivatization step of the free thiols at 45°C for 25 min and CZE analysis conducted within 14 min in the running buffer containing 16 mmol/L pH 7.0 sodium citrate and 60% v/v ACN. The LODs (S/N = 3) ranged from 0.11 nmol/L for N-acetylcysteine to 0.31 nmol/L for γ-glutamylcysteine, which are better than or comparable to those reported with other derivatization-based CE-LIF methods. As the first trial of NIR CE-LIF method for thiol determination, the practical application of the proposed method has been validated by detecting thiols in cucumber and tomato samples with recoveries of 96.5-104.3%.

Dual labeling for simultaneous determination of nitric oxide, glutathione and cysteine in macrophage RAW264.7 cells by microchip electrophoresis with fluorescence detection.

A simple, rapid and efficient method based on microchip electrophoresis coupled with fluorescence detection (MCE-FLD) was developed for simultaneous determination of nitric oxide (NO), glutathione (GSH) and cysteine (Cys) using dual labeling strategy. Two highly reactive fluorogenic probes, 1,3,5,7-tetramethyl-8-(3',4'-diaminophenyl)-difluoroboradiaza-s-indacene (DAMBO) and 1,3,5,7-tetramethyl-8-phenyl-(2-maleimide)-difluoroboradiaza-s-indacene (TMPAB-o-M), were used for labeling NO and thiols, respectively, under physiological conditions. The rapid separation and sensitive detection of the derivatives were achieved on a glass microchip within 70s in a running buffer of 20mM H3Cit-Na2HPO4 solution (pH 7.4) containing 15% (v/v) acetonitrile at a separation voltage of 2400V. The limits of detection (S/N=3) for NO, GSH and Cys were 7.0, 3.0 and 2.0nM, respectively. The proposed method was validated by measuring intracellular levels of NO and biothiols in macrophage RAW264.7 cells.

Development of a potential method based on microchip electrophoresis with fluorescence detection for the sensitive determination of intracellular thiols in RAW264.7 cells.

This paper, for the first time, reported the development of a simple, rapid, and reliable method for the separation and sensitive determination of four thiol compounds including homocysteine, cysteine, glutathione, and N-acetylcysteine based on glass MCE with fluorescence detection using a highly reactive fluorogenic probe, 1,3,5,7-tetramethyl-8-phenyl-(2-maleimide)-difluoroboradiaza-s-indacene (TMPAB-o-M), as the labeling reagent. TMPAB-o-M reacted selectively with thiols to produce highly fluorescent derivatives and the highest derivatization efficiency was achieved within 6 min in physiological conditions. After the optimization of separation conditions, a baseline separation of the four thiol compounds was achieved with the detection limits ranging from 2 nM for glutathione to 4 nM for cysteine (S/N = 3) and RSDs (n = 5) in the range of 3.2-3.8%. The proposed method was significantly sensitive compared to those using electrochemical or even LIF detection in MCE-based setup reported previously, and applied to the determination of intracellular thiols in macrophage RAW264.7 cells.

Mannose-binding lectin inhibits monocyte proliferation through transforming growth factor-ß1 and p38 signaling pathways.

Mannose-binding lectin (MBL), a plasma C-type lectin, plays an important role in innate immunity. However, the interaction, and the consequences of it, between MBL and the immune system remain ill defined. We have investigated the contributing mechanisms and effects of MBL on the proliferation of human monocytes. At lower concentrations (≤4 µg/ml) MBL was shown to partially enhance monocyte proliferation. By contrast, at higher concentrations (8-20 µg/ml) of MBL, cell proliferation was markedly attenuated. MBL-induced growth inhibition was associated with G0/G1 arrest, down-regulation of cyclin D1/D3, cyclin-dependent kinase (Cdk) 2/Cdk4 and up-regulation of the Cdk inhibitory protein Cip1/p21. Additionally, MBL induced apoptosis, and did so through caspase-3 activation and poly ADP-ribose polymerase (PARP) cleavage. Moreover, transforming growth factor (TGF)-ß1 levels increased in the supernatants of MBL-stimulated monocyte cultures. We also found that MBL-dependent inhibition of monocyte proliferation could be reversed by the TGF-ß receptor antagonist SB-431542, or by anti-TGF-ß1 antibody, or by the mitogen-activated protein kinase (MAPK) inhibitors specific for p38 (SB203580), but not ERK (U0126) or JNK (SP600125). Thus, at high concentrations, MBL can affect the immune system by inhibiting monocyte proliferation, which suggests that MBL may exhibit anti-inflammatory effects.

Light and electron microscopic features of synovium in patients with psoriatic arthritis.

INTRODUCTION: Few ultrastructural studies have been reported in psoriatic arthritis (PsA). The authors report a series of synovial biopsies with emphasis on patients with early disease to look for distinctive light (LM) and electron microscopic (EM) features of possible importance. METHODS: The authors examined synovial biopsies obtained primarily by needle biopsy from 13 PsA patients using LM and/or EM. Sections from 12 patients were evaluated by LM for vascularity, synovial lining thickness, fibrin deposition, and inflammation via a semi-quantitative scale. Nine EM specimens were descriptively analyzed. Clinical, synovial fluid (SF), and radiographic characteristics were recorded. RESULTS: Patients were mostly male, with mean disease duration before biopsy of 2.19 ± 2.60 years; 7 patients had arthritis for less than 1 year. All patients had peripheral arthritis, 2 had axial involvement. SFs disclosed predominance of polymorphonuclear leukocytes. LM demonstrated proliferation of synovial lining cells, lymphocyte and plasma cell infiltration, as well as dramatic clusters of small vessels in the superficial synovium. EMs showed more detailed vascular changes, including small, subendothelial, electron-dense deposits and scattered microparticles in vessel lumens and walls. CONCLUSIONS: Prominent vascularity is confirmed as an important feature of some PsA. Vascular changes and other features, including the first EM demonstration of microparticles in PsA (identified as potent factors in other inflammatory joint diseases), are potential targets for therapy.

[Identification of a novel pathogenic mutation in MATP gene with oculocutaneous albinism type IV from a consanguineous marriage family].

OBJECTIVE: To clarify the pathogenicity-related genes and its mutations in an oculocutaneous albinism (OCA) patient from a consanguineous marriage family. METHODS: Polymerase chain reaction (PCR) and automatic DNA sequencing methods, chromosome walking by PCR amplification techniques (PCR-Walking), multiplex PCR in a single PCR tube with 3 primers bridging the breakpoint (Gap-PCR) and bioinformatic analysis were employed for screening the mutations and identifying the novel mutation in the patient and his family. RESULTS: A pathogenic deletion of 6365 bp was found in MATP gene with a range of c.562-1118 (± 2) to c.885 + 4923 (± 2). The patient was homozygous for deletion mutation. CONCLUSION: A large deletion mutation was first detected and identified in OCA4.