S100A6 Regulates nucleus pulposus cell apoptosis via Wnt/ß-catenin signaling pathway: an in vitro and in vivo study.

BACKGROUND: Intervertebral disc degeneration (IDD) is a common musculoskeletal degenerative disease, which often leads to low back pain and even disability, resulting in loss of labor ability and decreased quality of life. Although many progresses have been made in the current research, the underlying mechanism of IDD remains unclear. The apoptosis of nucleus pulposus (NP) cells (NPCs) is an important pathological mechanism in intervertebral disc degeneration (IDD). This study evaluated the relationship between S100A6 and NPCs and its underlying mechanism. METHODS: Mass spectrometry, bioinformatics, and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were used to screen and verify hub genes for IDD in human IVD specimens with different degeneration degrees. Western blotting, immunohistochemistry (IHC), and/or immunofluorescence (IF) were used to detect the expression level of S100A6 in human NP tissues and NPCs. The apoptotic phenotype of NPCs and Wnt/ß-catenin signaling pathway were evaluated using flow cytometry, western blotting, and IF. S100A6 was overexpressed or knocked down in NPCs to determine its impact on apoptosis and Wnt/ß-catenin signaling pathway activity. Moreover, we used the XAV-939 to inhibit and SKL2001 to activate the Wnt/ß-catenin signaling pathway. The therapeutic effect of S100A6 inhibition on IDD was also evaluated. RESULTS: S100A6 expression increased in IDD. In vitro, increased S100A6 expression promoted apoptosis in interleukin (IL)-1ß-induced NPCs. In contrast, the inhibition of S100A6 expression partially alleviated the progression of annulus fibrosus (AF) puncture-induced IDD in rats. Mechanistic studies revealed that S100A6 regulates NPC apoptosis via Wnt/ß-catenin signaling pathway. CONCLUSIONS: This study showed that S100A6 expression increased during IDD and promoted NPCs apoptosis by regulating the Wnt/ß-catenin signaling pathway, suggesting that S100A6 is a promising new therapeutic target for IDD.

POSTN promotes nucleus pulposus cell senescence and extracellular matrix metabolism via activing Wnt/ß-catenin and NF-κB signal pathway in intervertebral disc degeneration.

BACKGROUND: Intervertebral disc (IVD) degeneration (IVDD) is a prevalent condition contributing to back pain and disability. Periostin (POSTN) has emerged as a potential molecular marker and therapeutic target in IVDD, prompting further investigation into its role and mechanisms. METHODS: This study employs bioinformatics analysis combined with experimental validation to explore the role of POSTN in IVDD. Gene expression datasets from the GEO database were analyzed to identify genes associated with IVDD, and the effects of POSTN on rat nucleus pulposus (NP) cells senescence and extracellular matrix (ECM) metabolism were assessed both in vitro and in vivo. RESULTS: Elevated POSTN expression was observed in degenerated discs from IVDD patients, correlating with disease severity. In vitro experiments demonstrated that POSTN promotes NP cells senescence and ECM metabolism in a dose- and time-dependent manner. In vivo studies confirmed that POSTN inhibition can ameliorate the progression of IVDD. Further mechanistic insights revealed that POSTN may exert its effects by activating the NF-κB and Wnt/ß-catenin signaling pathways. CONCLUSION: POSTN plays a significant role in the pathogenesis of IVDD, with its upregulated expression closely linked to NP cells senescence and ECM metabolism. Targeting POSTN could offer a novel therapeutic strategy for IVDD. Additionally, the study predicts small molecules that may inhibit POSTN expression, providing potential candidates for the development of new drug treatments.

Notochordal cells: A potential therapeutic option for intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a prevalent musculoskeletal degenerative disorder worldwide, and ~40% of chronic low back pain cases are associated with IDD. Although the pathogenesis of IDD remains unclear, the reduction in nucleus pulposus cells (NPCs) and degradation of the extracellular matrix (ECM) are critical factors contributing to IDD. Notochordal cells (NCs), derived from the notochord, which rapidly degrades after birth and is eventually replaced by NPCs, play a crucial role in maintaining ECM homeostasis and preventing NPCs apoptosis. Current treatments for IDD only provide symptomatic relief, while lacking the ability to inhibit or reverse its progression. However, NCs and their secretions possess anti-inflammatory properties and promote NPCs proliferation, leading to ECM formation. Therefore, in recent years, NCs therapy targeting the underlying cause of IDD has emerged as a novel treatment strategy. This article provides a comprehensive review of the latest research progress on NCs for IDD, covering their biological characteristics, specific markers, possible mechanisms involved in IDD and therapeutic effects. It also highlights significant future directions in this field to facilitate further exploration of the pathogenesis of IDD and the development of new therapies based on NCs strategies.

Microbial succession and its correlation with the dynamics of flavor compounds involved in the fermentation of Longxi bacon.

Introduction: Longxi bacon is a traditional fermented meat from Gansu province, China. The ripening process of the bacon is crucial for quality and flavor. The aim of this study was to gain deeper knowledges on the bacterial and fungal community diversity and the changes of chemical components including fatty acids and volatile compounds at different time points during the ripening of the bacon and to understand the relationship between microbial profiles and the chemical components related the bacon flavor. Methods: Bacon samples were collected from days 0, 15, 30, 60 and 90. The bacterial and fungal compositions were analyzed with next generation sequencing targeting the 16S rDNA loci for bacteria and ITS loci for fungi. The fatty acids and the volatile components were analyzed by headspace solid phase micro extraction followed by gas chromatography/mass spectrometry (HS-SPME-GC/MS). Results: We found that the abundance of bacteria in bacon was higher than that of fungi, and Psychrobacter, Brochothrix, Phoma and Trichoderma was the dominant bacon's population. The largest contributors of volatiles were aldehydes, ketones and esters, and the main fatty acids were palmitic, oleic and linoleic acids. Pearson correlation analysis between microbial succession and key flavor substances showed that the production of Longxi bacon flavor is the result of a combination of bacteria and fungi. Ten bacteria genera and six fungi genera were determined as functional core microbiota for the flavor production based their dominance and functionality in microbial community. In addition, bacteria and fungi are involved in the oxidation and hydrolysis of fatty acids during the ripening of bacon, which also contributes to the formation of bacon flavor. Discussion: This study provides a comprehensive analysis of the key microbiota involved in shaping bacon's distinctive flavor. Here, the results presented should provide insight into the influence of the microenvironment on the microbial community in bacon and lay a foundation for further investigations into the food ecology of bacon.

The Role of S100A6 in Human Diseases: Molecular Mechanisms and Therapeutic Potential.

S100A6, also known as calcyclin, is a low-molecular-weight Ca2+-binding protein from the S100 family that contains two EF-hands. S100A6 is expressed in a variety of mammalian cells and tissues. It is also expressed in lung, colorectal, pancreatic, and liver cancers, as well as other cancers such as melanoma. S100A6 has many molecular functions related to cell proliferation, the cell cycle, cell differentiation, and the cytoskeleton. It is not only involved in tumor invasion, proliferation, and migration, but also the pathogenesis of other non-neoplastic diseases. In this review, we focus on the molecular mechanisms and potential therapeutic targets of S100A6 in tumors, nervous system diseases, leukemia, endometriosis, cardiovascular disease, osteoarthritis, and other related diseases.

Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer.

BACKGROUND: Triple negative breast cancer (TNBC) is a subtype of breast cancers with poor prognosis and targeted drug therapies are limited. To develop novel and efficacious therapies for TNBC, we developed a bispecific antibody F7AK3 that recognizes both trophoblast cell surface antigen 2 (TROP2) and CD3 and evaluated its antitumor activities both in vitro and in vivo. METHODS: The binding affinities of F7AK3 to the two targets, TROP2 and CD3, were evaluated by surface plasmon resonance. Binding of F7AK3 to TNBC cells and T cells were evaluated by flow cytometry. Immunofluorescent staining was performed to demonstrate the interactions between T cells with TNBC cells. The cytotoxicity of T cells against TNBC cell lines and primary tumor cells mediated by F7AK3 were determined in vitro. In vivo antitumor activity of F7AK3 was investigated in a xenograft TNBC tumor model, using immunodeficient mice that were reconstituted with human peripheral blood mononuclear cells. RESULTS: We demonstrated that F7AK3 binds specifically to human TROP2 and CD3 antigens, as well as TNBC cell lines and primary tumor cells. Human T cells can only be activated by F7AK3 in the presence of target tumor cells. F7AK3 recruits T cells to TROP2+ tumor cells in vitro and into tumor tissues in vivo. Antitumor growth activity of F7AK3 is observed in a xenograft TNBC tumor model. CONCLUSION: This study showed the antitumor potential of an anti-TROP2xCD3 bispecific antibody F7AK3 to TNBC tumor cells both in vitro and in vivo. These data demonstrate that F7AK3 has the potential to treat TNBC patients, which warrants further preclinical and clinical evaluation of the F7AK3 in advanced or metastatic TNBC patients.

Oncomirs miRNA-221/222 and Tumor Suppressors miRNA-199a/195 Are Crucial miRNAs in Liver Cancer: A Systematic Analysis.

BACKGROUND: The high mortality rate of hepatocellular carcinoma (HCC) is partly due to a lack of good diagnostic markers and treatment strategies. Recently, several microRNA (miRNA) profiling studies were conducted with HCC; however, their inconsistency means that their diagnostic or therapeutic value is debatable. AIMS: This study aims to systematically evaluate the consistency of miRNAs from multiple independent studies. METHODS: A systematic analysis of miRNAs from eligible publications was conducted, followed by real-time PCRs. The targets of highly consistent miRNAs were collected using online programs, followed by enrichment analyses for gene ontology terms and Kyoto encyclopedia of genes and genomes pathways. RESULTS: In total, 241 differentially expressed miRNAs were reported in 13 HCC profiling studies, of which 137 were upregulated and 104 downregulated. Among consistently upregulated miRNAs (cutoff > fourfold), miRNA-222, miRNA-21, miRNA-221, miRNA-210, and miRNA-224 were found increased in 8, 6, 6, 5, and 5 different studies, respectively. Among 137 downregulated miRNAs, miRNA-195, miRNA-199a, miRNA-125b, and miRNA-99a were reported in 8, 8, 5, and 5 studies, respectively. These results were confirmed by real-time PCR. Enrichment analyses demonstrated that programmed cell death and proliferation play important roles during the interplay of miRNA with HCC. CONCLUSIONS: miRNAs most consistently related to HCC are oncomirs miRNA-221/222 and tumor suppressors miRNA-199a/195.

White polymer light-emitting diodes based on star-shaped polymers with an orange dendritic phosphorescent core.

A series of new star-shaped polymers with a triphenylamine-based iridium(III) dendritic complex as the orange-emitting core and poly(9,9-dihexylfluorene) (PFH) chains as the blue-emitting arms is developed towards white polymer light-emitting diodes (WPLEDs). By fine-tuning the content of the orange phosphor, partial energy transfer and charge trapping from the blue backbone to the orange core is realized to achieve white light emission. Single-layer WPLEDs with the configuration of ITO (indium-tin oxide)/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)/polymer/CsF/Al exhibit a maximum current efficiency of 1.69 cd A(-1) and CIE coordinates of (0.35, 0.33), which is very close to the pure white-light point of (0.33, 0.33). To the best of our knowledge, this is the first report on star-shaped white-emitting single polymers that simultaneously consist of fluorescent and phosphorescent species.

Alcohol-processable organic amorphous electrolytes as an effective electron-injection layer for organic light-emitting diodes.

A new series of monoammonium-based organic electrolytes with the tetrafluoroborate (BF(4)(-)) counteranion have been synthesized. Replacing the pendant ethyl groups in the fluorenyl unit with 4-ethoxyphenyl groups dramatically improves both solubility and morphological stability. The characterization of the alcohol-processable amorphous ionic compounds as an electron-injection layer in organic light-emitting diodes (OLEDs) reveals that the organic electrolyte that comprises a rigid linear-conjugated unit provides better device performance, with respect to its counterpart containing a branched bulky moiety. The capability of these compounds to facilitate electron injection from air-stable aluminum metal is preliminarily discussed on the basis of the investigations of the electron-only devices and photovoltaic experiments.

Solution-processed, undoped, deep-blue organic light-emitting diodes based on starburst oligofluorenes with a planar triphenylamine core.

A series of starburst oligomers (T1-T3) that contained a fully diarylmethene-bridged triphenylamine core and oligofluorene arms were designed and synthesized through Suzuki cross-coupling reactions. Their thermal, photophysical, and electrochemical properties were also investigated. These materials showed high glass transition, in the range of 123-129 °C, and good film-forming abilities. They displayed deep-blue emission both in solution and as thin films. Solution-processed devices based on these oligomers exhibited highly efficient deep-blue electroluminescence and the device performances were significantly enhanced with the extension of the oligofluorene arms. The double-layered device that contained T3 as an emitter showed a maximum current efficiency of 3.83 cd A(-1) and a maximum external quantum efficiency of 4.19% with CIE coordinates of (0.16, 0.09), which are among the highest values for undoped deep-blue OLEDs that are based on solution-processable starburst oligomers.

Iridium phosphors with peripheral triphenylamine encapsulation: highly efficient solution-processed red electrophosphorescence.

The peripheral triphenylamine-encapsulated red-emitting iridium(III) complexes have been designed and synthesized. External quantum efficiency over 15% has been realized in single-layer polymer light-emitting diodes, which is the highest ever reported for solution-processed red phosphorescence.

Biosorption of copper and lead ions by waste beer yeast.

Locally available waste beer yeast, a byproduct of brewing industry, was found to be a low cost and promising adsorbent for adsorbing copper and lead ions from wastewater. In this work, biosorption of copper and lead ions on waste beer yeast was investigated in batch mode. The equilibrium adsorptive quantity was determined to be a function of the solution pH, contact time, beer yeast concentration, salt concentration and initial concentration of copper and lead ions. The experimental results were fitted well to the Langmuir and Freundlich model isotherms. According to the parameters of Langmuir isotherm, the maximum biosorption capacities of copper and lead ions onto beer yeast were 0.0228 and 0.0277 mmol g(-1) at 293 K, respectively. The negative values of the standard free energy change (DeltaG degrees ) indicate spontaneous nature of the process. Competitive biosorption of two metal ions was investigated in terms of sorption quantity. The amount of one metal ion adsorbed onto unit weight of biosorbent (q(e)) decreased with increasing the competing metal ion concentration. The binding capacity for lead is more than for copper. Ion exchange is probably one of the main mechanism during adsorptive process.

Copper(II) and lead(II) removal from aqueous solution in fixed-bed columns by manganese oxide coated zeolite.

The ability of manganese oxide coated zeolite (MOCZ) to adsorb copper and lead ions in single- (non-competitive) and binary- (competitive) component sorption systems was studied in fixed-bed column. The experiments were applied to quantify particle size, bed length, influent flow rate and influent metal concentration on breakthrough time during the removal of copper and lead ions from aqueous solutions using MOCZ column. Results of fixed-bed adsorption showed that the breakthrough time appeared to increase with increase of the bed length and decrease of influent metal concentration, but decreased with increase of the flow rate. The Thomas model was applied to adsorption of copper and lead ions at bed length, MOCZ particle size, different flow rate and different initial concentration to predict the breakthrough curves and to determine the characteristic parameters of the column useful for process design. The model was found suitable for describing the adsorption process of the dynamic behavior of the MOCZ column. The total adsorbed quantities, equilibrium uptakes and total removal percents of Cu(II) and Pb(II) related to the effluent volumes were determined by evaluating the breakthrough curves obtained at different conditions. The results suggested that MOCZ could be used as an adsorbent for an efficient removal of copper and lead ions from aqueous solution. The removal of metal ion was decreased when other additional heavy metal ion was added, but the total saturation capacity of MOCZ for copper and lead ions was not significantly decreased. This competitive adsorption also showed that adsorption of lead ions was decreased insignificantly when copper ions was added to the influent, whereas a dramatic decrease was observed on the adsorption of copper ions by the presence of lead ions. The removal of copper and lead ion by MOCZ columns followed the descending order: Pb(II) > Cu(II). The adsorbed copper and lead ions were easily desorbed from MOCZ with 0.5 mol l(-1) HNO3 solution.