Synovial osteoclastogenesis mediated by chondrocyte-secreted TNFα promotes TMJ condylar resorption.

BACKGROUND: Insufficient occlusal support (IOS) frequently causes subchondral bone absorption in temporomandibular joint osteoarthritis, and the underlying mechanism requires further investigation. METHODS: An IOS model was established by abrading rat molars. Micro-computed tomography was used to evaluate subchondral bone changes. Osteoclastogenesis of synovium-derived macrophages (SDMs) was confirmed by TRAP staining. Cartilage-specific TNFα depletion was achieved by intra-articular injection of adeno-associated virus carrying shRNA against murine TNFα under control of collagen type II. In vitro, chondrocytes were mechanically compressed and conditioned medium (CM) was collected to detect its ability to induce osteoclastogenesis of SDMs. RESULTS: Synovial osteoclastogenesis and condyle resorption were observed following IOS. TNFα level was elevated in hypertrophic chondrocytes after IOS. Synovial Wnt5a level increased, but Wnt3a level decreased after IOS. Depletion of TNFα in chondrocytes alleviated the synovial osteoclastogenesis and condyle bone resorption. In vitro compression of chondrocytes potentiated TNFα expression and secretion. The CM promoted osteoclastogenesis of SDMs, which were partially prohibited by TNFα neutralizing antibody. Furthermore, inhibition of Wnt3a facilitated osteoclastogenesis, whereas inhibition of Wnt5a partially suppressed osteoclastogenesis, of SDMs cultured in CM. CONCLUSION: Chondrocyte-secreted TNFα induced by IOS is a critical regulator of synovial osteoclastogenesis and subsequent condylar resorption, partially through non-canonical Wnt5a pathway.

Diallyl disulfide downregulating RhoGDI2 induces differentiation and inhibit invasion via the Rac1/Pak1/LIMK1 pathway in human leukemia HL-60 cells.

Leukemia is a type of disease in which hematopoietic stem cells proliferate clonally at the genetic level. We discovered previously by high-resolution mass spectrometry that diallyl disulfide (DADS), which is one of the effective ingredients of garlic, reduces the performance of RhoGDI2 from APL HL-60 cells. Although RhoGDI2 is oversubscribed in several cancer categories, the effect of RhoGDI2 in HL-60 cells has remained unexplained. We aimed to investigate the influence of RhoGDI2 on DADS-induced differentiation of HL-60 cells to elucidate the association among the effect of inhibition or over-expression of RhoGDI2 with HL-60 cell polarization, migration and invasion, which is important for establishing a novel generation of inducers to elicit leukemia cell polarization. Co-transfection with RhoGDI2-targeted miRNAs apparently decreases the malignant biological behavior of cells and upregulates cytopenias in DADS-treated HL-60 cell lines, which increases CD11b and decreases CD33 and mRNA levels of Rac1, PAK1 and LIMK1. Meanwhile, we generated HL-60 cell lines with high-expressing RhoGDI2. The proliferation, migration and invasion capacity of such cells were significantly increased by the treated with DADS, while the reduction capacity of the cells was decreased. There was a reduction in CD11b and an increase in CD33 production, as well as an increase in the mRNA levels of Rac1, PAK1 and LIMK1. It also confirmed that inhibition of RhoGDI2 attenuates the EMT cascade via the Rac1/Pak1/LIMK1 pathway, thereby inhibiting the malignant biological behavior of HL-60 cells. Thus, we considered that inhibition of RhoGDI2 expression might be a new therapeutic direction for the treatment of human promyelocytic leukemia. The anti-cancer property of DADS against HL-60 leukemia cells might be regulated by RhoGDI2 through the Rac1-Pak1-LIMK1 pathway, which provides new evidence for DADS as a clinical anti-cancer medicine.

[Effect of Sertraline on Serum Cytokine Levels in Adolescents With First-Episode Major Depressive Disorder].

Objective: To investigate the changes in serum inflammatory cytokines and the predictive factors for the efficacy of sertraline following medication therapy in adolescents with first-episode major depressive disorder (MDD). Methods: A total of 61 adolescent patients with first-episode drug-naïve MDD were enrolled for the MDD group and 55 healthy adolescents were enrolled for the healthy control (HC) group. Sertraline tablets were administered to the MDD group for 8 weeks after enrollment, while no medication was given to the HC group. In the MDD group, blood samples were collected to measure the cytokine levels and clinical data, including scores for the 17-item Hamilton Depression Scale (HAMD-17) and the Connor-Davidson Resilience Scale (CD-RISC), were assessed at baseline and at the end of the 8-week medication, whereas in the HC group, blood samples and clinical data were collected only at baseline. The correlation between the levels of serum inflammatory cytokines and depression severity in the MDD group was analyzed and stepwise linear regression of HAMD-17 in the MDD group was performed to find serologic indicators that could be used to predict the efficacy of sertraline. Results: At baseline, the levels of interleukin (IL)-1ß and IL-6 in the MDD group were significantly higher than those in the HC group (all P<0.0001), while the tumor necrosis factor (TNF)-α level in the MDD group was significantly lower than that in the HC group ( P=0.006). After 8 weeks of medication treatment, the MDD group showed decreased levels of IL-1ß and IL-6 and increased level of TNF-α compared to the pre-treatment levels. In addition, the HAMD-17 score, CD-RISC total score, and scores for perceived competence, trust and tolerance, and control, three factors of CD-RISC, all improved after treatment. There was no significant difference in serum cytokine levels at baseline between the subgroup showing response to the treatment and the non-responding subgroup. There was a weak correlation between IL-6 levels before and after treatment and CD-RISC scores and the scores for the trust and tolerance factor of CD-RISC before and after treatment. The baseline IL-1ß and TNF-α levels did not show significant effect on posttreatment HAMD-17 scores. Conclusions: Serum cytokine levels of adolescents with first-episode MDD differ significantly from those of healthy adolescents. Although IL-6 was found to be correlated with depression severity, there was not enough support for it to be used as a predictor of the antidepression efficacy of sertraline.

[Sequencing Analysis of miRNAs in Brain-Derived Exosomes of Adolescent Mice With Depression-Like Behaviors].

Objective: To explore the differential expression of microRNAs (miRNAs) in brain-derived exosomes (BDEs) of adolescent mice with depression-like behavior. Methods: The experimental group consisted of susceptible adolescent mice exposed to chronic social defeat stress (CSDS), and sucrose preference test (SPT) and open field test (OFT) were performed to evaluate their depression-like behaviors. BDEs were extracted by ultracentrifugation (UC). The morphology, particle size, and surface marker proteins of BDEs were examined by transmission electron microscopy, nano-flow cytometry and Western blot. The expression of miRNA in BDEs was evaluated by high-throughput RNA sequencing. GO enrichment analysis and KEGG pathway enrichment analysis were carried out based on bioinformatics. Results: The particle size of BDEs ranged between 50 to 100 nm and they displayed a typical disc-shaped vesicle structure. TSG101 and syntenin, the exosome-positive proteins, were detected. In the BDEs of mice with depression-like behaviors induced by CSDS, 13 miRNAs were significantly upregulated and 4 miRNAs were significantly downregulated. Go and KEGG analysis showed that differentially expressed miRNAs were significantly enriched in PI3K-Akt signaling pathway, axonal guidance, and hypoxic response. Conclusion: It was found in this study that exosomal miRNAs in brain tissue might be involved in such biological processes as insulin resistance, neuroplasticity, and hypoxic response, thereby regulating brain functions and causing depression-like behaviors.

Risk factors and treatment of rectal stenosis after transanal endoscopic microsurgery.

AIM: Rectal stenosis is a relatively rare complication after transanal endoscopic microsurgery (TEM). This study aims to identify the predictive parameters for stenosis and the application of TEM in the treatment. METHOD: The clinical data of patients who underwent TEM for rectal adenoma and early cancer from 2008 to 2019 were retrospectively reviewed. We compared the clinicopathological characteristics of patients with stenosis and those without stenosis and analysed the risk factors for stenosis. Treatment outcomes of stenosis with TEM were evaluated. RESULTS: A total of 230 patients were enrolled in this study. Overall, the postoperative complication rate was 11.7% (27/230), including eight (3.5%) patients with stenosis. Patients with stenosis exhibited a higher rate of tumour showing a laterally spreading morphology (P = 0.048), a wider circumferential extent of mucosal defect (P < 0.001), a shorter distance of the tumour from the anal verge (P = 0.001) and a wider longitudinal extent of mucosal defect (P = 0.027). A circumferential extent of mucosal defect >3/4 (OR 94.945, 95% CI 3.611-2496.41, P = 0.006) was identified as the only independent risk factor for stenosis. The four patients with both stenosis and clinical symptoms were treated by incising the stenosis ring using the TEM platform; the stenosis was cured, and symptoms disappeared after one to four courses of treatment. CONCLUSIONS: Circumferential extent of mucosal defect ≥3/4 was an independent risk factor for stenosis in treating rectal adenoma and early cancer with TEM. Incision of the stenosis ring using the TEM platform is an effective strategy for treating stenosis.

Compromised dynamic cerebral autoregulation is a hemodynamic marker for predicting poor prognosis even with good recanalization after endovascular thrombectomy.

PURPOSE: In patients undergoing endovascular thrombectomy (EVT) with acute ischemic stroke (AIS), dynamic cerebral autoregulation (dCA) may minimize neurological injury from blood pressure fluctuations. This study set out to investigate the function of dCA in predicting clinical outcomes following EVT. METHODS: 43 AIS of the middle cerebral or internal carotid artery patients underwent with EVT, and 43 healthy individuals (controls) were enrolled in this case control research. The dCA was evaluated using transcranial Doppler 12 h and five days after EVT. The transfer function analysis was used to derive the dCA parameters, such as phase, gain, and coherence. The modified Rankin scale (mRS) at 3 months after EVT was used to assess the clinical outcomes. Thefavorable outcome group was defined with mRS ≤2 and the unfavorable outcome group was defined with mRS score of 3-6. Logistic regression analysis was performed to determine the risk factors of clinical outcomes. RESULTS: A significant impairment in dCA was observed on the ipsilateral side after EVT, particularly in patients with unfavorable outcomes. After 5 days, the ipsilateral phase was associated with poor functional outcomes (adjusted odds ratio [OR] = 0.911, 95% confidence interval [CI]: 0.854-0.972; P = 0.005) and the area under the curve (AUC) (AUC, 0.878, [95% CI: 0.756-1.000] P < 0.001) (optimal cutoff, 35.0°). Phase change was an independent predictor of clinical outcomes from 12 h to 5 days after EVT (adjusted OR = 1.061, 95% CI: 1.016-1.109, P = 0.008). CONCLUSIONS: dCA is impaired in patients with AIS after EVT. Change in dCA could be an independent factor related to the clinical outcomes.

Assessment of pesticide exposure to applicators during spraying in orchards with a stretcher-mounted sprayer.

Various health risk assessment models have been developed to evaluate occupational pesticide exposure in China. However, there has been limited investigation into the relationship between health risks and pesticide spraying in orchards. In this study, we analyzed pesticide exposure of applicators while spraying with a stretcher-mounted sprayer in orchards located in four different climatic regions. All garments' unit exposure (UE) demonstrated a right-skewed distribution, with gloves and shins accounting for the highest proportion of dermal pesticide exposure. We observed little difference in dermal and inhalation UE levels between apple and citrus orchards, except for pesticide exposure levels on wipes and faces. While 57% of the inhalation UE distribution variance was attributed to clustering and location effects, no significant differences were observed in dermal exposure levels. We evaluated the impact of different levels of protective clothing on pesticide exposure levels, according to applicators' working habits in China. Our findings revealed that improved levels of protection significantly reduced dermal exposure to pesticides, particularly when wearing gloves during spraying with a stretcher-mounted sprayer. Based on our empirical data, we utilized a simple random sampling model and an intercept-only lognormal mixed model to estimate dermal and inhalation exposure levels. The estimated dermal UE was accurate to within 3-fold with 95% confidence, and half of the estimated inhalation UE was acceptable according to the fold relative accuracy (fRA). Our established and verified statistics for dermal and inhalation UE can be utilized to evaluate the potential pesticide exposure to applicators during spraying in orchards with a stretcher-mounted sprayer.

Personality traits predict treatment outcome of an antidepressant in untreated adolescents with depression: An 8-week, open-label, flexible-dose study.

BACKGROUND: Antidepressant response in adults with major depressive disorder (MDD) is probably influenced by personality dimensions. However, personality dimensions in depression and their association with antidepressant treatment in adolescents are relatively unknown. We sought to investigate whether personality traits (PTs) can influence antidepressant treatment response in adolescents with depression. METHODS: Eighty-two adolescents with MDD who had completed the 8 weeks of treatment with selective serotonin reuptake inhibitors (SSRI) were enrolled. The Revised NEO Five-Factor Inventory (NEO-FFI-R) was used to measure their personality at baseline, and the 17-item Hamilton Depression Rating Scale (HAMD-17) and Children's Depression Rating Scale-Revised (CDRS-R) were used to evaluate depressive symptoms at baseline and 8 weeks. Moreover, logistic regression was performed to investigate the relationship between personality dimensions and antidepressant response. Receiver operating characteristic analyses were employed to determine the accuracy of a PT-based model in predicting the antidepressant response rate. RESULTS: Adolescents with MDD had significantly different PTs at baseline. Multivariable logistic regression analysis showed that extroversion scores were associated with response to antidepressant treatment, the lower the extroversion score, the better the response to antidepressant treatment, after correcting for variables with significant differences and trends or all potential confounding variables. It was also found that the combination of disease duration, extraversion-gregariousness, and agreeableness-trust effectively predicted antidepressant response in adolescents with MDD, with a sensitivity of 79.4 % and specificity of 68.7 %. CONCLUSION: Personality dysfunction in adolescents is associated with MDD. The antidepressant treatment response is influenced by the degree of extroversion in adolescents with MDD.

Effects of manganese deficiency on serum hormones and biochemical markers of bone metabolism in chicks.

In order to investigate the effect of manganese (Mn) deficiency on bone metabolism in chicks, ninety 1-day-old male Arbor Acre chicks were randomly divided into 3 groups and each group were given a diet having a different concentration of Mn (60 mg kg(-1), control group; 40 mg kg(-1), Mn-deficient group I; 8.7 mg kg(-1), Mn-deficient group II). The serum was collected at 42 days old. Tests were performed to evaluate the changes in the levels of PTH, CT, ALP, TrACP, HOP TNF-alpha, OC, Mn and Ca in the serum of the chicks and the results showed that the levels of CT, ALP, TrACP, HOP, and Mn decreased markedly (P < 0.05), while PTH, Ca, and TNF-alpha increased markedly (P < 0.05) due to manganese deficiency in the diet, which indicates that Mn deficiency results in disorder of bone regulatory hormones and enzymes of bone metabolism in the serum.

Epidemiological survey of warts in Chinese military recruits: A cross-sectional and follow-up study.

Background: Warts are very common in military personnel, either at war or during peace times. However, little is known about the prevalence and natural course of warts in military recruits in China. Objective: To investigate the prevalence and natural course of warts in Chinese military recruits. Methods: In this cross-sectional study, the head, face, neck, hands, and feet of 3093 Chinese military recruits aged 16-25 years in Shanghai were examined for the presence of warts upon enlistment medical examinations. Questionnaires were distributed to collect the general information of the participants before the survey. All the patients were followed up by telephone interview for 11-20 months. Results: The prevalence rate of warts in Chinese military recruits was 2.49%. The diagnosis of most cases was common and plantar warts, which were usually less than 1 cm in diameter and with mild discomfort. Multivariate logistic regression analysis showed that smoking and sharing personal items with others were risk factors. Coming from southern China was a protective factor. Over 2/3 of patients recovered within 1 year and the type, number, and size of warts and treatment choice did not predict resolution.Study limitations and Conclusions This study demonstrated that warts had a relative lower morbidity and a higher spontaneous resolution rate in Chinese military recruits. The telephone interviews following the initial survey and the limitations of a cross-sectional study were the main drawbacks.

A resting-state electroencephalographic microstates study in depressed adolescents with non-suicidal self-injury.

Neuroimaging studies have revealed abnormal brain activities in depressed teenagers who engage in non-suicidal self-injury (NSSI). We used resting-state electroencephalography (EEG) microstate analysis, which indicates the brief overlap of brain network activation for exploring the characteristics of large-scale cortical activities in depressed adolescents engaged with NSSI to clarify the underlying temporal mechanism. A modified k-means cluster algorithm was used to segment 64-channel resting-state EEG data into microstates. Data from 27 healthy adolescents, 37 adolescents with major depressive disorder (MDD), and 53 adolescents with both MDD and NSSI were examined in this study. The resting-state microstate parameters were compared among groups using the one-way ANOVA and Spearman correlation. Then the associations between significantly different microstate parameters and the depressive severity and self-harming data in the patient groups were further analyzed. The MDD group had higher contribution (p < 0.01), occurrence (p < 0.01) of microstate A, and higher microstate E→A transition (p < 0.05) than the HC and the NSSI group. The MDD group showed a distinctly longer duration (p < 0.05) of microstate A and microstate A→C transition than the HC. The transition probability from B to C was increased in the NSSI group compared to the HC. In the MDD group, the HAMD correlated with the duration of microstate A (Spearman's rho = 0.34, p = 0.044), as the PHQ-9 correlated with its occurrence (Spearman's rho = 0.37, p = 0.028). This research revealed that whereas depressive adolescents with NSSI and MDD displayed similar patterns with healthy controls in EEG microstate, the MDD group did not. Additionally, the non-random transition from microstate E→A may protect against recent self-harm in adolescents with MDD.

Serum extracellular vesicle microRNA dysregulation and childhood trauma in adolescents with major depressive disorder.

Major depressive disorder (MDD) seriously endangers adolescent mental and physical health. Extracellular vesicles (EVs) are mediators of cellular communication and are involved in many physiological brain processes. Although EV miRNAshave been implicated in adults with major psychiatric disorders, investigation into their effects in adolescent MDDremains scarce. In discovery set, we conducted a genome-wide miRNA sequencing of serum EVs from 9 untreated adolescents with MDD and 8 matched healthy controls (HCs), identifying 32 differentially expressed miRNAs (18 upregulated and 14 downregulated). In the validation set, 8 differentially expressed and highly enriched miRNAs were verified in independent samples using RT-PCR, with 4 (miR-450a-2-3p, miR-3691-5p, miR-556-3p, and miR-2115-3p) of the 8 miRNAs found to be significantly elevated in 34 untreated adolescents with MDD compared with 38 HCs and consistent with the sequencing results. After the Bonferroni correction, we found that three miRNAs (miR-450a-2-3p, miR-556-3p, and miR-2115-3p) were still significantly different. Among them, miR-450a-2-3p showed the most markeddifferential expression and was able to diagnose disease with 67.6% sensitivity and 84.2% specificity. Furthermore, miR-450a-2-3p partially mediated the associations between total childhood trauma, emotional abuse, and physical neglect and adolescent MDD. We also found that the combination of miR-450a-2-3p and emotional abuse could effectively diagnose MDD in adolescents with 82.4% sensitivity and 81.6% specificity. Our data demonstrate the association of serum EV miRNA dysregulation with MDD pathophysiology and, furthermore, show that miRNAs may mediate the relationship between early stress and MDD susceptibility. We also provide a valid integrated model for the diagnosis of adolescent MDD.

Characterizing the critical features when personalizing antihypertensive drugs using spectrum analysis and machine learning methods.

Globally, methods of controlling blood pressure in hypertension patients remain inefficient. The difficulty of prescribing appropriate drugs specific to a patient's clinical features serves as one of the most important factors. Characterizing the critical drug-related features, just like that of the antibacterial spectrum (where each item is sensitive to the targeted drug's effectiveness or a specified indication), may help a doctor easily prescribe appropriate drugs by matching a patient's attributes with drug-related features, and effectiveness of the selected drugs would also be ascertained. In this study, we aimed to apply data mining methods to obtain the clinical characteristics spectrum or important clinical features of five frequently used drugs (Irbesartan, Metoprolol, Felodipine, Amlodipine, and Levamlodipine) for hypertension control by comparing successful and unsuccessful cases. Spectrum analysis based on a statistical method and five algorithms based on machine learning were used to extract the critical clinical features. A visualized relative weight matrix was then achieved by combining the results from the characteristic spectrum and machine learning-based methods. Our results indicated that the five targeted antihypertension agents had different importance orders of the 15 relative clinical features. Clinical analysis showed that the extracted important clinical attributes of the five drugs were both reasonable and meaningful in the selection of hypertension treatment. Therefore, our study provided a data-driven reference for the personalization of clinical antihypertensive drugs.

miR-143 Inhibits Cell Proliferation of Gastric Cancer Cells Through Targeting GATA6.

Recent studies have suggested that the dysregulation of microRNAs (miRNAs) plays a critical role in the progression of human cancers, including gastric cancer (GC). miR-143 had been reported to function as a tumor suppressor in GC. However, the exact molecular mechanism of how miR-143 participates in GC progression remains to be determined. In this present study, we revealed that the expression of miR-143 was significantly downregulated in human GC tissues and cell lines compared with normal tissues and a normal gastric epithelium cell line. In addition, upregulation of the expression of miR-143 in a GC cell line inhibited cell proliferation and induced cell cycle arrested in the G0/G1 phase. Furthermore, GATA6 was identified as a direct target of miR-143 in GC using the luciferase reporter assay. Upregulation of miR-143 inhibited the expression of GATA6 in GC cell lines. Moreover, the overexpression of GATA6 could attenuate the effect of miR-143 on cell proliferation in the GC cell lines. Collectively, these data indicated that miR-143 plays a tumor suppressor role partly through regulating the expression of GATA6 in GC. Therefore, targeting miR-143 may be a novel therapeutic method for GC.

A sequential injection analysis/chemiluminescent plant tissue-based biosensor system for the determination of diamine.

In this paper, a new chemiluminescent plant tissue-based biosensor for diamine detection was presented by employing sequential injection analysis (SIA), which facilitates precise fluidic handling and lower consumption of sample and reagents. Pea-seedling tissue acted as the molecular recognition element and was packed in a mini-PTFE column and further incorporated in the SIA system. The analysis of diamines, such as putrescine and cadaverine, is based on an enzymatic conversion which takes place in the plant tissue column to produce hydrogen peroxide. The formed hydrogen peroxide was detected by a chemiluminescence reaction involving luminol and Co(2+). Under the optimal conditions, the linear calibration graphs were obtained within 0.2-80 microM (putrescine) and 0.5-100 microM (cadaverine). The detection limits of 0.03 and 0.06 microM were achieved for putrescine and cadaverine, respectively, along with the relative standard deviations of 2.14% and 3.08% (n=11) and a sampling frequency of 40 h(-1). The present biosensor has been used for the analysis of diamine in fish samples with an acceptable accuracy.

A novel flow-injection chemiluminescence system for the determination of guanine.

A novel flow-injection chemiluminescence (CL) method for the determination of guanine was developed. The procedure is based on the CL reaction of guanine with hydrogen peroxide in borax buffer (pH 8.5) with Co2+ as a catalyst. The calibration graph is linear within the range of 3 x 10(-7)-9 x 10(-5) g/mL. A detection limit of 1 x 10(-7) g/mL, along with a relative standard deviation of 2.23% (3 x 10(-7) g/mL guanine, n = 11), were obtained. The present procedure was applied to the measurement of guanine in urine with recoveries of 97.5-107.5%. A possible CL mechanism of the reaction system is proposed.