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Objective: We aimed to determine the association between serum receptor activator of nuclear factor-kappa B ligand (sRANKL) levels and ankylosing spondylitis (AS) in Chinese patients. Methods: The PubMed, Cochrane Library, Embase, Chinese Biomedical Database, Web of Science, China National Knowledge Infrastructure, VIP, and Wan Fang databases were searched for studies conducted before October 1, 2020, without language restrictions. STATA version 12.0 and Revman version 5.3 were used to analyze the data. The standard mean differences (SMDs) and corresponding 95% confidence intervals (95% CIs) were calculated. Results: Twelve clinical case–control studies, including 585 patients with AS and 423 healthy controls, were included. The combined SMD for sRANKL suggested that the sRANKL level was significantly higher in Chinese patients with AS than in healthy controls (SMD: 3.27, 95% CI 2.11–4.43, P < 0.00001). Serum RANKL-related factor osteoprotegerin (OPG) levels (SMD: 0.86, 95% CI 0.09–1.64, P < 0.03) were lower in the Chinese patients with AS than in healthy controls, and the RANKL/OPG ratio (SMD = 1.05, 95% CI 0.64–1.46, P < 0.00001) in Chinese patients with AS was approximately the same as that of healthy controls. Subgroup analysis indicated that patients from North and South China had higher sRANKL levels than controls; the sRANKL levels of patients from South China were higher in the subgroup with a Bath Ankylosing Spondylitis Functional Index (BASFI) of > 4 than those of patients in other subgroups. In terms of duration, patients with AS for > 8 years had higher sRANKL levels than health controls. Other subgroup analyses were conducted by region, language, source of control, age, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). In these subgroups, the sRANKL levels were significantly higher in the patients with AS than in healthy controls. The BASFI and BASDAI were sources of heterogeneity. Conclusions: The sRANKL levels are higher in Chinese patients with AS, especially among those from South China. sRANKL levels may be positively correlated with the pathogenesis of AS among Chinese patients. [ABSTRACT FROM AUTHOR]

Abstract PIWI family member piwil1 , which associates with Piwi-interacting RNA (piRNA), is responsible in regulation of germ cell differentiation and maintenance of reproductive stem cells. In this study, we analyzed the piwil1 gene in Paralichthys olivaceus. Bioinformatics analysis and structure prediction showed that piwil1 had the conserved domains: PAZ domain and PIWI domain. Expression analysis during embryonic development implied that piwil1 gene was maternally inherited. The tissue distribution showed a sexually dimorphic gene expression pattern, with higher expression level in testis than ovary. In situ hybridization results demonstrated that piwil1 was predominantly distributed in oogonia, oocytes, sertoli cells and spermatocytes. A CpG island was predicted in the 5′-flanking region of piwil1 gene, and its methylation levels showed significant disparity between males and females, indicating that the sexually dimorphic expression of piwil1 gene might be regulated by methylation. Furthermore, we explored the distinct roles of human chorionic gonadotropin and 17α-methyltestosterone in regulating the expression of piwil1 , and found that piwil1 was interacting with the HPG axis hormones. These results indicated that piwil1 might play a crucial role in gonadal development and gametogenesis in Paralichthys olivaceus. Highlights • Piwil1 transcripts are more abundant in the testis than in the ovary. • Piwil1 gene is maternally inherited. • Piwil1 which is regulated by methylation and HPG axis participates in gonadal development and gametogenesis. [ABSTRACT FROM AUTHOR]

Melanoma, which originates from neural crest derived melanocytes, causes severe pain and even death to numerous patients. Previous studies reported that Notchless Homolog 1 (NLE1) plays an important role in cell proliferation, transcription and signal transduction. However, the clinical significance and biological behavior of NLE1 in melanoma remain a mystery. Thus, the role of NLE1 in melanoma was investigated in vitro and in vivo. The expression of NLE1 in melanoma was elevated and the expression level was positively correlated with lymphatic metastasis and tumor stage. In addition, NLE1 knockdown by shRNA specifically inhibited proliferation, enhanced the apoptotic sensitivity and hindered migration of melanoma cells in vitro. Mice xenograft model further showed that NLE1 knockdown could inhibit the tumor formation of melanoma in vivo. Additionally, the induction of apoptosis of melanoma cells by NLE1 knockdown required the participation of a series of apoptosis-related proteins. Besides, NLE1 can activate the PI3K/AKT signaling pathway. In summary, NLE1 was involved in the development and progression of melanoma, which may be a novel potential target for molecular therapy of melanoma. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the association between monocyte chemotactic protein-1 (MCP-1) and osteoarthritis. Methods: We searched PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), VIP (Chinese database), and Wan Fang (Chinese database) (before May 10, 2020), with no language limitations. STATA version 12.0 and Revman version 5.3 were used for data analysis. The standard mean difference (SMD) and corresponding 95% confidence intervals (95% CIs) were calculated. Nine clinical studies, including 376 patients with osteoarthritis and 306 healthy controls, were evaluated. Results: The combined SMDs of MCP-1 expression levels suggested that MCP-1 expression was significantly higher in patients with osteoarthritis than healthy controls (SMD = 1.97, 95% CI = 0.66–3.28, p = 0.003). Moreover, subgroup analysis implied that osteoarthritis patients from both Asians and mixed populations had higher MCP-1 expression levels than controls, whereas Caucasians did not (p > 0.05). Serum MCP-1 levels (SMD = 2.83, 95% CI = 1.07–4.6, p < 0.00001) were significantly higher in patients with osteoarthritis than in controls; however, this difference was not significant in synovial fluid and cartilage tissue. Subgroup analysis for ethnicity showed that MCP-1 levels were significantly higher in Chinese, Dutch, and Brazilian patients with osteoarthritis than in control groups, although significant differences were not observed for American and Italian subgroups. Conclusions: Our meta-analysis demonstrated that MCP-1 expression levels were higher in patients with osteoarthritis than in healthy controls and that MCP-1 may play important roles in the progression of osteoarthritis. Serum MCP-1 levels may serve as a potential biomarker for the diagnosis of osteoarthritis. [ABSTRACT FROM AUTHOR]

• Pyroptosis, apoptosis, and necroptosis drive IVDD. • KA inhibits PANoptosis, delays IVDD by upregulating TAK1. • Targeting TAK1 may be a promising therapeutic approach for IVDD therapy. Low back pain (LBP) is most commonly caused by intervertebral disc degeneration (IVDD). Pyroptosis, apoptosis, and necroptosis are crucial in IVDD pathogenesis; however, possible simultaneous occurrence in IVDD and co-regulation between the pathways and the regulatory mechanisms have not been investigated. PANoptosis is a regulated cell death (RCD) pathway with the key characteristics of pyroptosis, apoptosis, and necroptosis. This study revealed that tert -butyl hydroperoxide (TBHP) altered the expression of key proteins involved in PANoptosis in nucleus pulposus cells (NPCs). Furthermore, the natural product Kongensin A (KA), which has potential anti-necrotic and anti-inflammatory properties, inhibited PANoptosis. TAK1, often referred to as mitogen-activated protein kinase kinase kinase 7 (Map3k7), is a key regulator of innate immunity, cell death, inflammation, and cellular homeostasis; however, the physiological roles and regulatory mechanisms underlying IVDD remain unclear. In this study, we discovered that KA can upregulate TAK1 expression in NPCs, -which inhibits PANoptosis by suppressing oxidative stress. In conclusion, our results suggest that KA inhibits PANoptosis and delays IVDD progression in NPCs by upregulating TAK1 expression to maintain mitochondrial redox balance. Consequently, targeting TAK1 may be a promising therapeutic approach for IVDD therapy. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a progressive age-related disease characterised by pathological changes in the synovium, articular cartilage, and subchondral bone, significantly reducing the patients' quality of life. This study investigated the role of glucocorticoids, specifically dexamethasone, in OA progression, with a particular focus on their effects on chondrocytes. Although glucocorticoids are commonly used for OA pain relief, our research demonstrated that high concentrations of dexamethasone may accelerate OA progression by enhancing the ability of reactive oxygen species to inhibit chondrocyte autophagy, resulting in cell death and accelerated cartilage degeneration. Despite reports on the acceleration of pathogenesis and cartilage damage in some patients of OA taking corticosteroids, the mechanism behind the same has not been investigated. This necessitates an investigation of the concentration-dependent changes in the cartilage cells upon dexamethasone administration. In addition, the protective effect of PPAR γ on chondrocytes can prevent the decrease in chondrocyte autophagy and delay cartilage degeneration. Therefore, our study suggests that the therapeutic use of glucocorticoids in OA treatment should be more nuanced considering their potential detrimental effects. Future investigations should focus on the mechanisms underlying the glucocorticoid-mediated modulation of cell death processes, which could provide insights into new therapeutic strategies for OA treatment. • We studied the role of dexamethasone in osteoarthritis (OA) progression. • High concentrations of dexamethasone accelerate OA progression. • Effects of PPAR γ on chondrocyte can prevent reduced chondrocyte autophagy. • Therapeutic use of glucocorticoids in OA treatment should be nuanced. [ABSTRACT FROM AUTHOR]

P450c17, a key enzyme in the steroid generation pathway, plays an important role in the production of sex steroid and cortisol. In this study, two cyp17 gene isoforms, Pocyp17-I and Pocyp17-II were isolated from Paralichthys olivaceus gonads. Domain architecture analysis of Pocyp17-I and Pocyp17-II revealed that they had three regions important to enzymatic function. Structural analysis showed that Pocyp17-I and Pocyp17-II had 8 and 9 exons respectively, and the difference was caused by the insertion of an extra intron (intron1) in the latter. Quantitative real-time polymerase chain reaction results indicated that the expression of these two genes showed sexually dimorphism that Pocyp17-I and Pocyp17-II were highest expressed in testis and ovary, respectively. The in situ hybridization analysis of gonads indicated that Pocyp17-I and Pocyp17-II mRNA were both detected in oocytes, spermatocytes and Sertoli cells. After injection of androgen and estrogen (17α-methyltestosterone, 17β-estradiol) of different concentrations, the expression level of Pocyp17-I decreased significantly (P < 0.01), whereas estrogen had no influence on Pocyp17-II , but androgen upregulated the expression of Pocyp17-II (P < 0.05). Moreover, Pocyp17-I expression level was down-regulated significantly by NR0b1 but up-regulated by NR5a2 (P < 0.05), whereas Pocyp17-II expression level was down-regulated significantly by NR0b1 and NR5a2 (P < 0.05). All these results demonstrated that there were differences in expression patterns, feedback actions of sex hormones and transcriptional regulations between cyp17-I and cyp17-II , which revealed that cyp17-I and cyp17-II might perform different functions in sex hormones biosynthesis and gonadal differentiation in Japanese flounder. • Pocyp17-I and Pocyp17-II were highest expressed in testis and ovary, respectively. • Sex hormones and transcription factors have different regulatory effects on Pocyp17-I and Pocyp17-II. • cyp17-I and cyp17-II might perform different functions in androgen and estrogen biosynthesis and gonadal differentiation in P. olivaceus. [ABSTRACT FROM AUTHOR]

Plasma perfusion is one of the primary therapies for hepatic failure. However, biocompatibility and toxins removal of plasma perfusion adsorbents are mutual constraints. Herein, a novel bifunctional blood purification membrane structure is proposed, which can remove toxins via "filtration-adsorption". The internal surface of membrane has excellent biocompatibility. Meanwhile, the external surface can adsorb toxins. When blood flows in internal surface, toxins in plasma can be filtrated through membrane and adsorbed on the external surface. Herein, plasma separation membrane with excellent biocompatibility was prepared firstly. Then, the external surface was modified by β-cyclodextrin to construct bilirubin adsorption functional layer. XPS, ATR-FTIR and FE-SEM demonstrated that β-cyclodextrin was grafted on the external surface without modifying the internal surface. The bovine serum albumin sieving coefficient of membrane reached (97.8 ± 1.9)%. The water flux reached (1084 ± 30)L.m2.h−1. Bilirubin adsorption capacity of the external surface reached 12.8 mg/g via "filtration-adsorption". Bilirubin competitive adsorption coefficient was 9.1. The internal surface was similar to original plasma separation membrane, which had excellent biocompatibility due to low hemolysis and blood cells adsorption. Thus, the bifunctional blood purification membrane can remove bilirubin safely via one-step "filtration-adsorption". The structure design of membrane provides a new blood purification treatment scheme for clinical hepatic failure. [Display omitted] • A new bifunctional blood purification membrane structure is proposed. • It owns bilirubin removal external surface and blood compatible internal surface. • It is innovative to treat hepatic failure by one-step "filtration-adsorption". [ABSTRACT FROM AUTHOR]

Japanese flounder (Paralichthys olivaceus) is an economically important flatfish endemic to Asia that faces natural challenges, such as heat shock and bacterial infection. Here, we investigated whether heat shock protein 20 (hsp20) in Japanese flounder played a role in immune reactions against Edwardsiella tarda. Hsp20 is ubiquitously produced by cells in the stress response; it not only functions as a chaperone and housekeeping protein but also participates in the immune response during infection. In this study, we identified and annotated 13 hsp20 genes using bioinformatic methods in Japanese flounder. Phylogenetic and selection pressure analysis showed that the hsp20 genes were evolutionarily-constrained and their function was conserved. Hsp20 genes are also involved in the embryogenesis and act as the sentinel role in an unchallenged organism. Moreover, the regulated expression patterns of hsp20 genes after E. tarda infection were examined for the first time in Japanese flounder. Eleven out of 13 genes were differentially expressed after bacterial challenge, which indicated that they may be involved in disease response genes or as disease defence against pathogens. These results provide valuable information for clarifying the evolutionary relationship of the hsp20 genes, and early insights into the immune functions of hsp20 genes in Japanese flounder. • A full set of 13 hsp20s were identified and characterized in Japanese flounder genome. • The hsp20 genes were evolving-constrained and function conserved by phylogenetic and selection pressure analysis. • Most hsp20 genes were regulated in a time-specific, tissue-specific pattern after bacterial infection. [ABSTRACT FROM AUTHOR]