This study aimed to develop and evaluate barium and calcium microcapsules as candidates for scaffolding in artificial dermal papilla. Dermal papilla cells (DPCs) were isolated and cultured by one-step collagenase treatment. The DPC-Ba and DPC-Ca microcapsules were prepared by using a specially designed, high-voltage, electric-field droplet generator. Selected microcapsules were assessed for long-term inductive properties with xenotransplantation into Sprague-Dawley rat ears. Both barium and calcium microcapsules maintained xenogenic dermal papilla cells in an immunoisolated environment and induced the formation of hair follicle structures. Calcium microcapsules showed better biocompatibility, permeability, and cell viability in comparison with barium microcapsules. Before 18 weeks, calcium microcapsules gathered together, with no substantial immune response. After 32 weeks, some microcapsules were near inflammatory cells and wrapped with fiber. A few large hair follicles were found. Control samples showed no marked changes at the implantation site. Barium microcapsules were superior to calcium microcapsules in structural and mechanical stability. The cells encapsulated in hydrogel barium microcapsules exhibited higher short-term viability. This study established a model to culture DPCs in 3D culture conditions. Barium microcapsules may be useful in short-term transplantation study. Calcium microcapsules may provide an effective scaffold for the development of artificial dermal papilla.

The objective of this study is to investigate the potential association of the NLRP3 rs10754558 and CARD8 rs2043211 polymorphisms with the occurrence and prognosis of CAD. Gene polymorphisms were analyzed using the ABI PRISM-Snapshot multiplex method in 515 CAD patients and 401 control subjects. The serum level of IL-1β was investigated by ELISA assays. The clinical endpoints were evaluated during a median follow-up period of 32 months. The NLRP3 rs10754558 gene polymorphism was significantly associated with the occurrence of CAD, while the CARD8 rs2043211 gene polymorphism was not involved. Patients carrying G allele of NLRP3 rs10754558 had more severe coronary artery stenosis. Multivariable analysis revealed a significant association of the G allele with major adverse cardiac event. The serum IL-1β concentrations in patients with GG genotype were significantly increased compared with those in the patients with CC genotype. Our findings for the first time show that the NLRP3 rs10754558 polymorphism is involved in the occurrence of CAD in the Chinese Han population; and G allele can effectively predict clinical outcome of CAD. The G allele susceptibility to CAD is maybe associated with the increased level of serum IL-1β.

Coxsackievirus 16 (CA16) causes hand, foot, and mouth disease (HFMD) in young children and infants, and it can lead to fatal neurological complications. This study investigated antiviral effects of Siji Antiviral Mixture (SAM) on CA16 in neonatal mice and the protective effects of SAM on CA16 induced brain injuries. Neonatal BALB/c mice and SH-SY5Y cells were used and injected with CA16 stains to study the efficacy. ELISA and Western blotting were used to measure the cytokines levels and proteins expression. Genes transduction was also used to verify interaction mechanism. As the results shown, SAM could reduce the clinical scores at the beginning and delay disease development in vivo. Treatment with SAM decreased the levels of LDH, CK-MB, caspase 3 and Bax, ER stress, and inflammatory reaction induced by CA16 infection. Further siRNA transfection results showed that CA16 induced ER stress and inflammatory reaction through PERK/STAT3/NF-κB signaling and the protective effects of SAM might be through inhibiting PERK/STAT3/NF-κB signaling. HPLC analysis showed fingerprint profiles of SAM had 42 chromatographic peaks. Collectively, our study highlighted distinct roles of SAM in inhibiting CA16 infection and brain injury. The molecular mechanism of SAM might be through inhibiting PERK/STAT3/NF-κB signaling.

A novel antisense oligonucleotide (ASO) carrier, polyethylenimine conjugated to linoleic acid (PEI-LA), was synthesized and evaluated for delivery of LOR-2501 to tumor cells. LOR-2501 is an ASO targeting ribonucleotide reductase R1 subunit (RRM1). In this study, PEI-LA was synthesized by reacting PEI (Mw ~ 800) with linoleoyl chloride. Gel retardation assay showed complete complexation between PEI-LA and LOR-2501 at N/P ratio above 8. No significant cytotoxicity was observed with these complexes at the tested dosage levels. Interestingly, at N/P ratio of >6, levels of cellular uptake of PEI-LA/LOR-2501 were double that of PEI/LOR-2501 complexes of the same N/P ratio. PEI-LA/LOR-2501 induced downregulation of 64% and 70% of RRM1 at mRNA and protein levels, respectively. The highest transfection activity was shown by PEI-LA/LOR-2501 complexes at N/P ratio of 10. Finally, using pathway specific inhibitors, clathrin-mediated endocytosis was shown to be the principle mechanism of cellular internalization of these complexes. In conclusion, PEI-LA is a promising agent for the delivery of ASOs and warrants further investigation.

This study aimed to explore whether bone marrow- (BM-) derived endothelial progenitor cells (EPCs) contributing to monocrotaline- (MCT-) induced pulmonary arterial hypertension (PAH) in rats via modulating store-operated Ca2+ channels (SOC).

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by sacroiliitis and spinal rigidity of the axial joints. The role of oxidative stress and increased proinflammatory cytokines is well documented in AS pathogenesis. Punicalagin (2,3-hexahydroxydiphenoyl-gallagyl-D-glucose), an ellagitannin widely present in pomegranates, is found to exhibit potent anti-inflammatory, antiproliferative, and antioxidative effects. The present study was undertaken to investigate the effects of punicalagin in a rodent model of AS.

Attenuating β amyloid- (Aβ-) induced microglial activation is considered to be effective in treating Alzheimer's disease (AD). Berberine (BBR) can reduce microglial activation in Aβ-treated microglial cells; the mechanism, however, is still illusive. Silencing of cytokine signaling factor 1 (SOCS1) is the primary regulator of many cytokines involved in immune reactions, whose upregulation can reverse the activation of microglial cells. Microglia could be activated into two different statuses, classic activated state (M1 state) and alternative activated state (M2 state), and M1 state is harmful, but M2 is beneficial. In the present study, N9 microglial cells were exposed to Aβ to imitate microglial activation in AD. And Western blot and immunocytochemistry were taken to observe inducible nitric oxide synthase (iNOS), Arginase-1 (Arg-1), and SOCS1 expressions, and the enzyme-linked immunosorbent assay (ELISA) was used to measure inflammatory and neurotrophic factor release. Compared with the normal cultured control cells, Aβ exposure markedly increased the level of microglial M1 state markers (P < 0.05), including iNOS protein expression, tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6 releases, and BBR administration upregulated SOSC1 expression and the level of microglial M2 state markers (P < 0.05), such as Arg-1 expression, brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF) releases, downregulating the SOCS1 expression by using siRNA, however, significantly reversed the BBR-induced effects on microglial M1 and M2 state markers and SOCS1 expression (P < 0.05). These findings indicated that BBR can inhibit Aβ-induced microglial activation via modulating the microglial M1/M2 activated state, and SOCS1 mediates the process.

To explore more efficient treatments for chronic obstructive pulmonary disease (COPD), effective-component compatibility of Bufei Yishen formula III (ECC-BYF III) and electroacupuncture were tested on rats with COPD, and silent information regulator transcript-1 (SIRT1)/nuclear factor-kappaB (NF-κB) signaling was further investigated to interpret the therapy.

Chronic obstructive pulmonary disease (COPD) is a complex disease caused by the disturbance of genetic and environmental factors. Single-nucleotide polymorphisms (SNPs) play a vital role in the genetic dissection of complex diseases. In-depth analysis of SNP-related information could recognize disease-associated biomarkers and further uncover the genetic mechanism of complex diseases. Risk-related variants might act on the disease by affecting gene expression and gene function. Through integrating SNP disease association study and expression quantitative trait loci (eQTL) analysis, as well as functional enrichment of containing known causal genes, four risk SNPs and four corresponding susceptibility genes were identified utilizing next-generation sequencing (NGS) data of COPD. Of the four risk SNPs, one could be found in the SNPedia database that stored disease-related SNPs and has been linked to a disease in the literature. Four genes showed significant differences from the perspective of normal/disease or variant/nonvariant samples, as well as the high performance of sample classification. It is speculated that the four susceptibility genes could be used as biomarkers of COPD. Furthermore, three of our susceptibility genes have been confirmed in the literature to be associated with COPD. Among them, two genes had an impact on the significance of expression correlation of known causal genes they interact with, respectively. Overall, this research may present novel insights into the diagnosis and pathogenesis of COPD and susceptibility gene identification of other complex diseases.

MicroRNAs are small noncoding RNAs involved in numerous biological processes. Emerging pieces of evidence suggest that microRNAs play important roles in osteogenesis and skeletal homeostasis. Recent studies indicated the significant regulation function of mir-21 in osteogenesis in vitro, but little information is known about its veritable functions in vivo. In the present study, we aimed to investigate the effect of mir-21 intervention on osteogenic differentiation of rats bone marrow derived mesenchymal stem cells (rBMSCs) and repair capacity in rats closed femur fracture model with internal fixation. The results showed that the upregulation of mir-21 not only increased the expression of osteopontin and alkaline phosphatase in rBMSCs but also promoted mineralization in the condition of osteogenic induction. Furthermore, the bone healing properties were also improved in fracture healing model according to the results of micro-CT, mechanical test, and histological analysis. The current study confirms that the overexpression of mir-21 could promote osteogenesis and accelerate bone fracture healing, which may contribute to a new therapeutic way for fracture repair.

Neuropathic pain (NP) is a devastating complication following nerve injury, and it can be alleviated by regulating neuroimmune direction. We aimed to explore the neuroimmune mechanism and identify some new diagnostic or therapeutic targets for NP treatment via bioinformatic analysis.

Exercise-induced physiological cardiac hypertrophy is generally considered to be a type of adaptive change after exercise training and is beneficial for cardiovascular diseases. This study aims at investigating exercise-regulated microRNAs (miRNAs) and their potential biological pathways. Here, we collected 23 miRNAs from 8 published studies. MirPath v.3 from the DIANA tools website was used to execute the analysis, and TargetScan was used to predict the target genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed to identify potential pathways and functional annotations associated with exercise-induced physiological cardiac hypertrophy. Various miRNA targets and molecular pathways, such as Fatty acid elongation, Arrhythmogenic right ventricular cardiomyopathy (ARVC), and ECM-receptor interaction, were identified. This study could prompt the understanding of the regulatory mechanisms underlying exercise-induced physiological cardiac hypertrophy.

The femoral anterior bow is an important factor in matching a femoral implant to a femur. However, its morphology in the Chinese population has rarely been reported. In this study, a three-dimensional measurement approach was adopted to provide accurate data. The aim was to supply a reference for designing a long-stemmed femoral prosthesis that is more suitable for Chinese people.

Aiming to reveal the role of ADCS-Exos in secretion of inflammatory factors, Th17 and regulatory T (Treg) cell differentiation from naïve CD4+ T cells in hypertrophic scaring formation and maturation is explored. ELISA, qRT-PCR, and immunoblotting are performed to assay the local inflammatory factors IL-6, IL-10, IL-17A, and TNF-α, and transcriptional factors of RORϒt and Foxp3, in scaring tissue from patients and mice wound models treated with or without ADCS-Exos. Immunohistochemistry staining and immunoblotting are conducted to assay the extracellular matrix (ECM) deposition in vitro and in vivo. The results show that IL-6, IL-10, IL-17A, TNF-α, RORϒt, and Foxp3 are increased on mRNA and protein levels in hypertrophic scaring compared with atrophic scaring and normal skin. Naïve CD4+ T cells treated with ADCS-Exos in vitro can produce significantly less IL-6, IL-17A, TNF-α, and RORϒt and more IL-10 and Foxp3 on mRNA and protein levels. In addition, mice in ADSC-Exos-treated group demonstrate less collagen deposition; decreased IL-17A, TNF-α, and RORϒt; and increased IL-10 and Foxp3 production.

Noncoding RNA (ncRNA) is a kind of RNA that plays a key role in a variety of biological processes, illnesses, and tumours despite the fact that it cannot be translated into proteins. The HT29 colon cancer cell line was utilized to create a 5-FU drug-resistant cell strain (control group), a lentivirus SNHG20 carrier (OE-SNHG20 group), and an SNHG20 shRNA carrier (SNHG20 shRNA carrier group) (SE-SNHG20 group). To determine the expression of cell SNHG20, a real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was utilized, and cholecystokinin-octapeptide (CCK-8) was used to detect the difference in 5-FU inhibitory concentration 50. The goal of the study was to see how variations in long nonencoding ribonucleic acid (lncRNA) SNHG20 expression affect colon cancer cell 5-fluorouracil (5-FU) chemotherapeutic sensitivity by collecting colon cancer and normal para cancer tissues and analysing the differences in SNHG20 expression. The ability of cell cladogenesis was tested using platform cladogenesis. Cell apoptosis was detected using flow cytometry. Western blots revealed the presence of protein phosphatidylinositol kinase (PI3K), protein kinase B (AKT), caspase-3, e-cadherin, and matrix metalloproteinase 9 (MMP-9) enzymes. The findings revealed that SNHG20 expression was considerably upregulated (P < 0.05) in colon cancer tissue and 5-FU drug-resistant colon cancer cells. Cell 5-FU IC50, cell cladogenesis, cell survival rate, and MMP-9, P-PI3K, and P-AKT expression were all significantly improved. Cell apoptosis and expressions of E-cadherin and caspase-3, on the other hand, were considerably decreased (P < 0.05). Cell 5-FU IC50, cell cladogenesis, cell survival rate, and the expressions of MMP-9, P-PI3K, and P-AKT were all significantly lower in the SE-SNHG20 group, although cell apoptosis and the expressions of E-cadherin and caspase-3 were significantly higher (P < 0.05). The results revealed that lncRNA SNHG20 could inhibit the chemotherapeutic sensitivity of colon cancer cells to 5-FU by regulating PI3K/AKT pathways. The inhibition of lncRNA SNHG20 expression could promote the apoptosis and proliferation of 5-FU-resistant colon cancer cells.

Colorectal cancer is one of the most common and fatal tumors. However, molecular mechanisms underlying carcinogenesis of colorectal cancer remain largely undefined. Here, we explored the expression and function of Nodal in colon cancer stem cells (CCSCs). Nodal and its receptors were present in numerous human colorectal cancer cell lines. NODAL and ALK-4 were coexpressed in human colon cancerous tissues, and NODAL, CD24, and CD44, markers for CCSCs, were expressed at higher levels in human colon cancerous tissues than adjacent noncancerous colon tissues. Human CCSCs were isolated by magnetic activated cell sorting using anti-CD24 and anti-CD44. Nodal transcript and protein were hardly detectable in CD44- or CD24-negative human colorectal cancer cell lines, whereas Nodal and its receptors were present in CCSCs. Notably, Nodal facilitated spheroid formation of human CCSCs, and phosphorylation of Smad2 and Smad3 was activated by Nodal in cells of spheres derived from human CCSCs. Collectively, these results suggest that Nodal promotes the self-renewal of human CCSCs and mediate carcinogenesis of human colorectal cancer via an autocrine manner through Smad2/3 pathway. This study provides a novel insight into molecular mechanisms controlling fate of human CCSCs and offers new targets for gene therapy of human colorectal cancer.

Background. Epicardial adipose tissue (EAT) is identified as an atypical fat depot surrounding the heart with a putative role in the involvement of metabolic disorders, including obesity, type-2 diabetes mellitus, and atherosclerosis. We profiled miRNAs in EAT of metabolic patients with coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM) versus metabolically healthy patients by microarray. Compared to metabolically healthy patients, we identified forty-two miRNAs that are differentially expressed in patients with CAD and T2DM from Xinjiang, China. Eleven miRNAs were selected as potential novel miRNAs according to P value and fold change. Then the potential novel miRNAs targeted genes were predicted via TargetScan, PicTar, and miRTarbase, and the function of the target genes was predicted via Gene Ontology (GO) analysis while the enriched KEGG pathway analyses of the miRNAs targeted genes were performed by bioinformatics software DAVID. Then protein-protein interaction networks of the targeted gene were conducted by online software STRING. Finally, using microarray, bioinformatics approaches revealed the possible molecular mechanisms pathogenesis of CAD and T2DM. A total of 11 differentially expressed miRNAs were identified and among them, hsa-miR-4687-3p drew specific attention. Bioinformatics analysis revealed that insulin signaling pathway is the central way involved in the progression of metabolic disorders. Conclusions. The current findings support the fact that miRNAs are involved in the pathogenesis of metabolic disorders in EAT of CAD patients with T2DM, and validation of the results of these miRNAs by independent and prospective study is certainly warranted.

MiRNAs have been widely analyzed in the occurrence and development of many diseases, including pterygium. This study aimed to identify the key genes and miRNAs in pterygium and to explore the underlying molecular mechanisms.

To evaluate Roux-en-Y and Billroth II reconstruction following pancreaticoduodenectomy (PD).

Osteoarthritis (OA) is a very common chronic joint dysfunction, and there is currently a poor understanding of its etiology and pathogenesis. Therefore, there are no active disease-modifying drugs currently available for clinical treatment. Several natural compounds have been shown to play a role in inhibiting OA progression. The present study is aimed at investigating the curative effects of acacetin, a natural flavonoid compound, against OA. Our results demonstrated that MMP-1, MMP-3, and MMP-13 were highly expressed in OA specimens. Acacetin inhibited the interleukin-1β- (IL-1β-) induced expression of MMP-1, MMP-3, and MMP-13in chondrocytes by blocking nuclear factor-κB (NF-κB) signaling pathways. Furthermore, we found that acacetin suppressed OA progression and inhibited the expression of MMP-1, MMP-3, and MMP-13 in ACLT-induced OA mice. Taken together, our study revealed that acacetin may serve as a potential drug for treating OA.