Fibroblast growth factor-21 may be a potential novel drug for preventing the development of traumatic TMJ bony ankylosis

AbstractTrauma is the leading cause of temporomandibular joint (TMJ) bony ankylosis. The treatment of the condition poses a significant challenge because of the high incidence of recurrence. We previously proposed a new view that the development of traumatic TMJ bony ankylosis may be a course similar to hypertrophic nonunion, and the ensuing animal experiments preliminarily verified this view through histological analysis and molecular biology examination. In view of the similarity between bone healing and bony ankylosis, and the importance of recruitment and differentiation of mesenchymal stem cells (MSCs) during the course of bone healing, it is reasonable to select MSCs as the breakthrough point for prevention of bony ankylosis. Recent studies reveal that fibroblast growth factor 21 (FGF21), a key mediator of peroxisome proliferator-activated receptor-γ (PPARγ), can promote adipocyte differentiation, inhibit osteoblast differentiation of MSCs and stimulate osteoclast activity by activation of PPARγ. Therefore, we hypothesize that local FGF21 injection may prohibit the onset of traumatic TMJ bony ankylosis through formation of a fat pad separating the condyle from the glenoid fossa, inhibition of new bone formation and promotion of bone resorption in the joint space, which thus may be a potential novel treatment for TMJ bony ankylosis

Up-regulation of corticotropin releasing hormone is associated with the downregulation of corticotropin releasing hormone binding protein and up-regulation of IL- 33 and IL-8 expression in psoriasis

Purpose: To determine the expression of corticotropin releasing hormone (CRH) in psoriasis and normal skin biopsy samples, and to correlate the expression of CRH with the expression of CRHBP and inflammatory cytokines IL-8 and IL-33.Methods: Psoriasis and normal skin biopsy samples were obtained from three psoriatic and three normal healthy patients. The mRNA expression was examined by quantitative real-time polymerase chain reaction (RT-PCR). Protein expression analysis was carried out by Western blotting and then further validated by immunohistochemistry.Results: The results of the present study revealed that the expression of CRH was highly significant (p < 0.0001) in psoriatic skin, compared to normal skin. Increase of CRH in psoriatic samples ranged from 2.7 to 3.5-fold. Expression of CRH was associated with the concomitant downregulation of CRHBP in all the psoriatic skin biopsy samples, with expression of CRHBP 3.0 to 6.2-fold lower in psoriatic skin than in normal skin. Analysis of mRNA expression of IL-8 and IL-33, revealed that expression of both IL-8 and IL-33 was significantly (p < 0.0001) upregulated in psoriatic skin samples while the expression of IL-8 and IL-33 was approximately 4.1- and 3.2-fold higher in psoriatic skin than in normal skin. The expression of CRHBP, IL-8 and IL-33 was further confirmed by western blotting and immunohistochemistry results.Conclusion: The results confirm that the expression of CRH is associated with the suppression of CRHBP and upregulation of IL-8 and IL-33.Keywords: Psoriasis, Corticotropin releasing hormone, Inflammatory cytokines, Interleukin, Skin biops

Tumor promoter TPA activates Wnt/β-catenin signaling in a casein kinase 1-dependent manner.

The tumor promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA) has been defined by its ability to promote tumorigenesis on carcinogen-initiated mouse skin. Activation of Wnt/β-catenin signaling has a decisive role in mouse skin carcinogenesis, but it remains unclear how TPA activates Wnt/β-catenin signaling in mouse skin carcinogenesis. Here, we found that TPA could enhance Wnt/β-catenin signaling in a casein kinase 1 (CK1) ε/δ-dependent manner. TPA stabilized CK1ε and enhanced its kinase activity. TPA further induced the phosphorylation of LRP6 at Thr1479 and Ser1490 and the formation of a CK1ε-LRP6-axin1 complex, leading to an increase in cytosolic β-catenin. Moreover, TPA increased the association of β-catenin with TCF4E in a CK1ε/δ-dependent way, resulting in the activation of Wnt target genes. Consistently, treatment with a selective CK1ε/δ inhibitor SR3029 suppressed TPA-induced skin tumor formation in vivo, probably through blocking Wnt/β-catenin signaling. Taken together, our study has identified a pathway by which TPA activates Wnt/β-catenin signaling

Iron(III) Chloride-catalyzed Nucleophilic Substitution of Propargylic Alcohols: A General and Efficient Approach for the Synthesis of 1,4-Diynes

A wide variety of 1,4-diynes have been constructed via a novel FeCl(3)-catalyzed coupling reaction of propargylic alcohols with alkynylsilanes. This synthetic approach provides a general, efficient, and economical route to 1,4-cliynes.National Natural Science Foundation of China[20772098, 21072159

What makes a good phorophyte? Predicting occupancy, species richness and abundance of vascular epiphytes in a lowland seasonal tropical forest

peer reviewedEpiphytes typically exhibit clustered distribution patterns, but predicting the spatial variation of their distribution at fine scales has long been a challenge. Taking advantage of a canopy crane giving access to 1.1 ha of lowland seasonal rainforest in Yunnan (China), we assess here which factors promote the probability that a given tree hosts epiphytes, and the variation of species richness and abundance of epiphytic spermatophytes and ferns among trees. Variation in epiphyte species richness as a function of host tree size, characteristics of its surrounding environment, topography and microclimatic conditions, were analyzed by Random Forest. Epiphytic spermatophytes and ferns occupied 2.3 and 10.8% of the available host trees, respectively. Significant models predicting which trees are more likely to host epiphytes than others were obtained, indicating that host tree characteristics and their local environment play a significant role in determining which host tree is most likely to be colonized. These models, as well as models for species richness and abundance, however, exhibited a moderate to low accuracy (r2 0.28 and 0.24 and of 0.12 and 0.14 for spermatophyte and fern richness and abundance, respectively). The best predictor of the presence of epiphytes on a tree, of its epiphytic species richness and abundance, was its DBH. In ferns, however, two peaks of species richness were observed, representing shade-loving ferns on small trees and sun-loving ferns on large trees. Microclimatic conditions and light intensity were the second best factor accounting for variation in species richness and abundance among trees. The contribution of liana infestation, host tree identity, and characteristics of neighboring trees were marginal. Our inclusion of a large number of host-tree characteristics and their local environment did not allow for an apparent improvement of model accuracy over studies with a more limited number of predictors, pointing to the role of chance upon tree colonization. Our results confirm the utmost importance of large trees with emergent canopies for the conservation of the epiphytic flora, but also indicate that epiphytic diversity assessments in tropical forests must also include small understorey trees, which should be further considered for conservation. The importance of the micro-climatic conditions that prevail at the level of each individual host tree further points to the necessity of maintaining a buffer zone around large host trees targeted for conservation

Thyroid function, renal function, and depression: an association study

ObjectiveTo investigate the correlations between thyroid function, renal function, and depression.MethodsClinical data of 67 patients with Major depressive disorder (MDD) and 36 healthy control subjects between 2018 and 2021 were collected to compare thyroid and renal function. Thyroid and renal functions of depressed patients were then correlated with the Hamilton Depression Rating Scale (HAMD) and the Hamilton Anxiety Rating Scale (HAMA).Spearman correlation analysis was used to find the correlation between renal function, thyroid function, and depression. A logistic regression was performed to find significant predictors of depression.ResultsTriiodothyronine protamine (T3), thyroxine (T4), free triiodothyronine protamine (FT3), uric acid, sodium, and anion gap were lower in the MDD group than in the control group (p < 0.05). Correlation analysis of thyroid function, renal function, and factor terms of HAMD in the MDD group suggested that diurnal variation, hopelessness, and depression level were positively correlated with thyrotropin (TSH) (p < 0.05). Cognitive disturbance, retardation, and depression level were negatively correlated with creatinine (p < 0.05). Diurnal variation was negatively correlated with sodium ion (p < 0.01); hopelessness and depression level were positively correlated with chloride ion (p < 0.05); diurnal variation, retardation, and depression level were negatively correlated with anion gap (p < 0.05). Diurnal variation (p < 0.01) and retardation (p < 0.05) were negatively correlated with osmolality. Cognitive disturbance and depression level were positively correlated with estimated glomerular filtration rate (eGFR) (p < 0.05). In the MDD group, correlation analysis of thyroid function, renal function, and HAMA factor terms suggested that the total HAMA score and anxiety level were positively correlated with chloride ion (p < 0.05); psychic anxiety, total HAMA score, and anxiety level were negatively correlated with anion gap (p < 0.05). Furthermore, a low level of anion gap was an independent risk factor for depression and anxiety levels (p < 0.05).ConclusionLow thyroid function and reduced waste metabolized by the kidneys in patients with MDD suggest a low intake and low metabolism in depressed patients. In addition, subtle fluctuations in the anion gap in depressed patients were strongly correlated with the degree of depression and anxiety

BCL9 and C9orf5 are associated with negative symptoms in schizophrenia: meta-analysis of two genome-wide association studies

Schizophrenia is a chronic and debilitating psychiatric condition affecting slightly more than 1% of the population worldwide and it is a multifactorial disorder with a high degree of heritability (80%) based on family and twin studies. Increasing lines of evidence suggest intermediate phenotypes/endophenotypes are more associated with causes of the disease and are less genetically complex than the broader disease spectrum. Negative symptoms in schizophrenia are attractive intermediate phenotypes based on their clinical and treatment response features. Therefore, our objective was to identify genetic variants underlying the negative symptoms of schizophrenia by analyzing two genome-wide association (GWA) data sets consisting of a total of 1,774 European-American patients and 2,726 controls. Logistic regression analysis of negative symptoms as a binary trait (adjusted for age and sex) was performed using PLINK. For meta-analysis of two datasets, the fixed-effect model in PLINK was applied. Through meta-analysis we identified 25 single nucleotide polymorphisms (SNPs) associated with negative symptoms with p\u3c5×10(-5). Especially we detected five SNPs in the first two genes/loci strongly associated with negative symptoms of schizophrenia (P(meta-analysis)\u3c6.22×10(-6)), which included three SNPs in the BCL9 gene: rs583583 showed the strongest association at a P(meta-analysis) of 6.00×10(-7) and two SNPs in the C9orf5 (the top SNP is rs643410 with a p = 1.29 ×10(-6)). Through meta-analysis, we identified several additional negative symptoms associated genes (ST3GAL1, RNF144, CTNNA3 and ZNF385D). This is the first report of the common variants influencing negative symptoms of schizophrenia. These results provide direct evidence of using of negative symptoms as an intermediate phenotype to dissect the complex genetics of schizophrenia. However, additional studies are warranted to examine the underlying mechanisms of these disease-associated SNPs in these genes