Application of Comprehensive Pelvic Floor Rehabilitation Therapy in Congestion Syndrome with Pelvic Oblique: A Case Report.

Background: Pelvic congestion syndrome (PCS), also known as ovarian vein syndrome, is one of the key causes of chronic pelvic pain. The present study combined pelvic floor myofascial manipulation, uterine conditioning, and improved Kegel exercise for the treatment of a PCS patient with pelvic inclination to provide a reference for clinical therapy. Case description: A 29-year-old female was admitted to our hospital on 20th April 2023, with the main complaint being repeated lower abdominal and lumbosacral pain with frequent urination (urine volume < 200 ml/time), external genital itching accompanied by increased secretion for more than 5 years. The patient was treated with pelvic floor myofascial manipulation, uterine conditioning, and improved Kegel exercise 6 times. Pelvic magnetic resonance imaging (MRI) examination, pelvic X-ray examination, overall posture assessment, and related functional status were observed and evaluated. Conclusions: After comprehensive pelvic floor rehabilitation treatment containing pelvic floor myofascial manipulation, uterine conditioning, and improved Kegel training, the symptoms and signs of the patient were significantly improved, and the effect was obvious.

Effects of pelvic floor myofascial manipulation intervention on primiparas and neonates during the second stage of vaginal delivery.

A prolonged second stage of vaginal delivery increases the risk of shoulder dystocia, unnecessary episiotomies and cesarean sections. However, no standardized method has been proposed to tackle this issue. The effects of pelvic floor myofascial manipulation intervention during the second stage of labor in primiparas and its prognostic value in neonatal postpartum outcomes remain unknown. In the present study, a total of 60 primiparas who were expecting a vaginal delivery in the Second Affiliated Hospital of Hainan Medical College (Haikou, China) between October 2021 and January 2022 were selected. These women were randomly assigned to a control group (standard intrapartum care) or an experimental group (pelvic floor myofascial manipulation for 15-20 min during the second stage of labor along with standard intrapartum care) using a random number table, with 28 patients in each group. There was no significant difference in age, gestational time or body mass index between the two groups before delivery, indicating that the baseline data were comparable. The second stage of labor duration, forced breath-holding time and postpartum hemorrhage volume in the experimental group were significantly lower than those in the control group. The pain visual analog scale scores, fatigue scores and neonatal Apgar scores in the experimental group were also significantly lower than those in the control group. The rate of episiotomy in the experimental group was lower than that in the control group, but the difference was not statistically significant. In conclusion, pelvic floor myofascial manipulation intervention during the second stage of labor for primiparas with vaginal delivery can reduce the duration of the second stage of labor, the amount of bleeding during labor and the pain during labor. Meanwhile, it has the potential to improve neonatal outcomes.

MXene-Based Current Collectors for Advanced Rechargeable Batteries.

As an indispensable component of rechargeable batteries, the current collector plays a crucial role in supporting the electrode materials and collecting the accumulated electrical energy. However, some key issues, like uneven resources, high weight percentage, electrolytic corrosion, and high-voltage instability, cannot meet the growing need for rechargeable batteries. In recent years, MXene-based current collectors have achieved considerable achievements due to its unique structure, large surface area, and high conductivity. The related research has increased significantly. Nonetheless, a comprehensive review of this area is seldom. Herein the applications and progress of MXene in current collector are systematically summarized and discussed. Meanwhile, some challenges and future directions are presented.

Caffeic acid attenuates tissue damage and inflammatory response in Klebsiella pneumonia by modulating AhR-Src-STAT3-IL-10 signaling pathway.

CA is a plant derivative with antibacterial and antiviral pharmacological effects, however, the therapeutic effect of CA on Klebsiella pneumonia and its mechanism study is still unclear. A rat KP model was established in vitro, a pneumonia cell model was established in vivo, the histopathological changes in the lungs were observed by HE staining after CA treatment, the expression of relevant inflammatory factors was detected by ELISA, the changes in the expression of proteins related to the AhR-Src-STAT3-IL-10 signaling pathway were detected by Western blot and immunofluorescence in the lungs, and the interactions between the proteins were verified by COIP relationship. The results showed that CA was able to attenuate the injury and inflammatory response of lung tissues, and molecular docking showed that there were binding sites between CA and AhR, and COIP demonstrated that AhR interacted with both STAT3 and Ser. In addition, CA was able to up-regulate the expression levels of pathway-related proteins of AhR, IL-10, p-Src, and p-STAT3, and AhR knockdown was able to reduce LPS-induced inflammatory responses and up-regulate pathway-related proteins, whereas CA treatment of AhR-knockdown-treated A549 cells did not show any statistically significant difference compared with the AhR knockdown group, demonstrating that CA exerts its pharmacological effects. These findings elucidated the mechanism of CA in the treatment of KP and demonstrated that CA is a potential therapeutic agent for KP.

Electrocatalytic hydrogenation of indigo by NiMoS: energy saving and conversion improving.

An NiMo alloy bonded with sulfur (NiMoS) exhibits enhanced surface affinity toward water and organic molecules, thereby enhancing electrocatalytic hydrogenation (ECH) reactions through synergistic effects. In industrial processes, indigo, an ancient dye employed in the denim industry, is typically chemically reduced using sodium dithionite. However, this process generates an excess of toxic sulfide, which heavily contaminates the environment. ECH is a sustainable alternative for indigo reduction due to its reduced reliance on chemicals and energy consumption. In this study, carbon-felt (CF)-supported NiMoS was synthesized in a two-step process. First, the NiMo alloy was electrodeposited onto the CF surface, followed by sulfidation in an oven at 600 °C. NiMoS exhibits a larger electrochemically active surface area and a smaller charge transfer resistance compared to pure Ni and NiMo. Furthermore, NiMoS demonstrates excellent thermodynamic and kinetic properties for water splitting in strong alkaline solutions (1.0 M KOH). Additionally, optimal reaction conditions for the ECH of indigo were explored. Under the conditions of a 1.0 M KOH hydroxide medium with 10% methanol (v/v), an indigo concentration of 5 g L-1, a reaction temperature of 70 °C, and a current density of 10 mA cm-2, NiMoS/CF achieved remarkable improvements in both conversion (99.2%) and Faraday efficiency (38.1%). The results of this experimental work offer valuable insights into the design and application of novel catalytic materials for the ECH of vat dyes, opening up new possibilities for sustainable and environmentally friendly processes in the dye industry.

Pelvic floor myofascial manipulation combined with Kegel exercise and mecobalamin in the treatment of atypical diabetic neurogenic bladder: a case report.

Background: Diabetic neurogenic bladder (DNB) is one of the autonomic neuropathies of diabetes mellitus (DM), with an incidence rate reaching 40-60%. This study combined bladder function rehabilitation training and mecobalamin to treat a patient with DNB to provide reference for clinical work. Case Description: A 67-year-old woman was admitted to our hospital on 5 December 2018, with a 3-year history of dysuria that had progressively worsened for 15 days. The patient was treated with pelvic floor myofascial manipulation combined with Kegel training and mecobalamin for 6 months. Pelvic organ prolapse (POP), pelvic floor surface electromyography (EMG), psychological status, and quality of life were evaluated before, during, and after treatment, and the changes in urodynamics were observed. After comprehensive rehabilitation treatment, the patient's POP, pelvic floor muscle strength, mental state, and quality of life were significantly improved. The results of the urodynamic examination showed that the patient's safe bladder capacity reached 500 mL after treatment, in contrast to the first safe bladder capacity measurement of 90 mL. The symptoms of ureteral reflux disappeared, the detrusor compliance increased from 2 to 20 mL/cmH2O, which roughly indicated a return to healthy function. However, there was no detrusor contraction in the bladder during urination. Conclusions: This patient achieved good curative effect after the treatment of comprehensive pelvic floor rehabilitation combined with mecobalamin. However, the safe capacity of the patient reported in this case showed a small bladder safe capacity, and the patient's detrusor muscle did not contract during urination. Thus, urination in this patient may be accomplished by increasing abdominal pressure. When treating patients with atypical neurogenic bladder, the adverse effects caused by excessive abdominal pressure and abdominal wall relaxation need to be considered.

Extraction of pigments from camellia seed husks and their application on silk fabrics.

To reuse camellia husk waste and expand the scope of natural dyes, this research proposes pigment extraction from camellia husks and investigates various properties when applied on silk fabrics. Single-factor experiments were used to screen and optimize the dyeing process. The extracted pigments and dyed fibers were analyzed and characterized by LC-MS, FTIR and SEM, respectively. Six metal mordants were compared with each other, and their possible mordanting mechanisms were proposed. Color fastness, UV resistance, and antioxidant and antibacterial properties were evaluated after dyeing. The results showed that the optimal dyeing process was as follows: dyestuff mass 50 g L-1, holding time 45 min, bath pH 3.0, holding temperature 100 °C. LC-MS and FTIR results showed that the pigments in the extracts were mainly dimeric and multimeric procyanidins. Metal ion addition increased the K/S value while the pre-mordanting method had a superior dyeing depth. The rubbing and washing fastness of the dyed fabric were all above grade 4.0. Meanwhile, the dyed sample exhibited favorable UV resistance, and antioxidant and antibacterial properties, including a UPF index of 63.4 and an inhibition rate of 98.74% and 97.39% for S. aureus and E. coli, respectively.

Cellular level of coenzyme Q increases with neuronal differentiation, playing an important role in neural elongations.

Deficiency of coenzyme Q has been reported in various neuro-logical diseases, and the behavior of this lipid in neurons has attracted attention. However, the behavior of this lipid in normal neurons remains unclear. In this study, we analyzed the concen-tration of coenzyme Q before and after neuronal differentiation. Nerve growth factor treatment of PC12 cells caused neurite outgrowth and neuronal differentiation, and the amount of intra-cellular coenzyme Q increased dramatically during this process. In addition, when the serum was removed from the culture medium of N1E-115 cells and the neurite outgrowth was confirmed, the intracellular coenzyme Q level also increased. To elucidate the role of the increased coenzyme Q, we administered nerve growth factor to PC12 cells with coenzyme Q synthesis inhibitors and found that coenzyme Q levels decreased, neurite outgrowth was impaired, and differentiation markers were reduced. These results indicate that coenzyme Q levels increase during neuronal differentiation and that this increase is important for neurite outgrowth.

Energy-Saving One-Step Pre-Treatment Using an Activated Sodium Percarbonate System and Its Bleaching Mechanism for Cotton Fabric.

The traditional pre-treatment of cotton fabric hardly meets the requirement of low carbon emissions due to its large energy consumption and wastewater discharge. In this study, a low-temperature and near-neutral strategy was designed by establishing a tetraacetylethylenediamine (TAED)-activated sodium percarbonate (SPC) system. First, the effects of SPC concentration, temperature and duration on the whiteness index (WI) and capillary effect of cotton fabrics were investigated. Particularly, excess SPC's ability to create an additional bleaching effect was studied. The optimized activated pre-treatment was compared with the traditional pre-treatment in terms of the bleaching effect and energy consumption. Further, the degradation of morin, which is one of the natural pigments in cotton, was carried out in a homogeneous TAED/SPC system to reveal the bleaching mechanism. Lastly, the application performance of the treated cotton was evaluated by characterizing the dyeability, mechanical properties, morphology, etc. The research results showed that temperature had a significant influence on both the WI and capillary effect, followed by the SPC concentration and duration. The WI was positively correlated with the SPC concentration, but excess SPC could not produce an obvious additional effect. The WI of the fabric increased by 67.6% after the optimized activated bleaching using 10 mmol/L SPC and 15 mmol/L TAED at 70 °C for 30 min. Compared with the traditional process performed at 95 °C for 45 min, the activated process produced approximately 39.3% energy savings. Research on the bleaching mechanism indicated that the reactive species that participated in degrading the morin were the hydroxyl radical and superoxide radical, and the contribution degree of the former was larger than that of the latter. Two degradation components with molecular weights of 180 and 154 were detected using mass spectroscopy. Based on this, the bleaching mechanism of the TAED/SPC system was proposed. Moreover, the fabric after the activated pre-treatment had a suitable dyeability and strength, a lower wax residual and a smoother and cleaner fiber surface. The encouraging results showed that TAED/SPC is a promising bleaching system that is conducive to the sustainable advance of the textile industry.

Pearson's Principle-Inspired Robust 2D Amorphous Ni-Fe-Co Ternary Hydroxides on Carbon Textile for High-Performance Electrocatalytic Water Splitting.

Layered double hydroxide (LDH) is widely used in electrocatalytic water splitting due to its good structural tunability, high intrinsic activity, and mild synthesis conditions, especially for flexible fiber-based catalysts. However, the poor stability of the interface between LDH and flexible carbon textile prepared by hydrothermal and electrodeposition methods greatly affects its active area and cyclic stability during deformation. Here, we report a salt-template-assisted method for the growth of two-dimensional (2D) amorphous ternary LDH based on dip-rolling technology. The robust and high-dimensional structure constructed by salt-template and fiber could achieve a carbon textile-based water splitting catalyst with high loading, strong catalytic activity, and good stability. The prepared 2D NiFeCo-LDH/CF electrode showed overpotentials of 220 mV and 151 mV in oxygen evolution and hydrogen evolution reactions, respectively, and simultaneously had no significant performance decrease after 100 consecutive bendings. This work provides a new strategy for efficiently designing robust, high-performance LDH on flexible fibers, which may have great potential in commercial applications.

A universal construction of robust interface between 2D conductive polymer and cellulose for textile supercapacitor.

Conductive polymer (CP) fabric is considered as the ideal electrode for flexible energy storage due to its light weight, good flexibility and high energy storage properties. However, the conventional polymer-coated cellulose fiber synthesized by liquid-phase oxidation polymerization always forms disordered assembly of polymer particles on fiber, which endures poor mechanical stability. Here, we report a two-dimensional (2D) CP based fabric electrode realized by a salt-template assisted vapor-phase polymerization method, which achieves robust coating of 2D CP on various cellulose fibers. Typically, the prepared 2D polypyrrole@cotton electrode displays a high specific capacitance (902.6 mF cm-2) and good cycling stability (86.5% capacitance retention after 12,000 cycles). The capacitance of flexible symmetrical device retains at more than 90% when it is bent to 180° after 1000 bending cycles. This work provides a new strategy for the robust interface between functional materials and cellulose fibers, and has great potential for commercial mass production.

Sodiophilic Mg2+ -Decorated Ti3 C2 MXene for Dendrite-Free Sodium Metal Batteries with Carbonate-Based Electrolytes.

The advantages of sodium metal, such as abundant resources, low cost, high capacity, and high working potential, make it a promising metal anode. Unfortunately, the hazardous dendrite growth of sodium metal is one of the major hindrances for the practical application of sodium metal batteries (SMBs). By applying multifunctional Mg(II)@Ti3 C2 MXene as the protective layer for commercial Cu foil, the wettability of the electrolyte on the current collector is dramatically improved with the suppression of sodium dendrites. Moreover, the first-principles calculations prove that the surface of Mg(0001) is able to establish a connection with Na(111) growth, with Mg acting as the nucleation seed for sodium. The experimental results indicate that even when a high areal capacity of sodium (2 mAh cm-2 ) is deposited, no sodium dendrite is observed. Electrochemical tests, including symmetric cells, Na||Cu asymmetric cells, and full cells, prove the sodiophilic character of Mg2+ -decorated Ti3 C2 MXene. The results may also create a new pathway for developing other dendrite-free metal anodes, such as Li/K/Zn/Ca/Mg.

Scalable Synthesis of Nano-Sized Bi for Separator Modifying in 5V-Class Lithium Metal Batteries and Potassium Ion Batteries Anodes.

With the advantages of high theoretical-specific capacity and lowest working potential, lithium metal anode is considered as the most promising anode for next-generation batteries. Here, a scalable dealloying method is developed to prepare nano-sized bismuth (Bi). It is found that the Bi-modification can not only enhance the wettability of the commercial polyethylene separator but also suppresses the lithium dendrite growth. With the nano-sized Bi modified separator, 5V-class lithium metal batteries with commercial carbonate-based electrolyte show a 91% capacity retention ratio after 800 cycles. First-principle calculations prove that lithium atoms tend to deposit smoothly on the Bi surface. Moreover, for potassium ion batteries, nano-sized Bi shows a stable cycling performance and high capacity. The results may be useful for the development of high-energy and high-safety batteries.

The rapid production of multiple transition metal carbides via microwave combustion under ambient conditions.

Transition metal carbides (TMCs) have attracted great interest owing to their potential applications for energy storage and electrocatalysis. But the synthesis of high-quality TMCs usually needs high energy consumption, long reaction times, or dangerous chemical reagents, limiting their practical application. Here, a microwave combustion method is developed to rapidly (∼2 min) produce transition metal carbides under ambient conditions. The as-synthesized TMCs (W2C, VC, Fe3C, NbC, TaC, and Mo2C) and rGO composites exhibit outstanding catalytic performance for the hydrogen evolution reaction (HER) over a broad range of pH values. This work highlights a novel strategy for the design and synthesis of transition metal carbides.

Scalable and Physical Synthesis of 2D Silicon from Bulk Layered Alloy for Lithium-Ion Batteries and Lithium Metal Batteries.

Owing to its distinctive structure and properties, 2D silicon (2DSi) has been widely applied in hydrogen storage, sensors, electronic device, catalysis, electrochemical energy storage, etc. However, scalable and low-cost fabrication of high-quality 2DSi remains a great challenge. In this work, a physical vacuum distillation method is designed to obtain high-quality 2DSi from a bulk layered calcium-silicon alloy. With this method, the lower boiling point calcium metal is evaporated to construct 2DSi and can be further recycled. The effect of vacuum conditions on morphology, components, and electrochemical properties is further explored. As an anode for lithium-ion batteries, the 2DSi delivers a stable cyclability of 835 mAh g-1 after 3000 cycles at 5000 mA g-1 (0.003025% capacity decay per cycle). The electrochemical performance enhancing mechanism is also probed. In addition, a 2D/2D flexible and binder-free paper by combining 2DSi with 2D MXene is constructed. As a lithiophilic nuclear agent for lithium metal anodes, the 2DSi can efficiently suppress the Li dendrite growth and reduce nucleation barriers, achieving a high Coulombic efficiency (98% at 1 mA cm-2, 97% at 2 mA cm-2) around 600 cycles and a long lifespan of 1000 h. The crystal growth difference of lithium metal on Cu foil and 2DSi is studied. This work may provide a pathway for green, low-cost, and scalable synthesis of 2D materials.

Efficient removal of heavy metal ions and organic dyes with cucurbit [8] uril-functionalized chitosan.

The development of a high-efficiency adsorption material is important for the simultaneous elimination of heavy metal ions and organic pollutants from wastewater. In the present work, a novel material was synthesized by grafting functionalized cucurbit [8] uril (CB[8]) onto chitosan (CS) chains via a CNC covalent bond (CB[8]-CS). This as-prepared material presented an unprecedented adsorption capacity. The maximum adsorption capacities (qm) were 1622.7 mg/g, 1172.7 mg/g, 1361.9 mg/g and 873.6 mg/g for the adsorption of reactive orange 5 (RO5), acidic blue 25 (AB25), reactive yellow 145 (RY145) and Pb2+ ions, respectively, which are far higher than the reported data. The simultaneous co-adsorption of dye and a heavy metal ion was tested with a mixed solution of 200 mg/L RO5 dye and Pb2+ ion, and the removal rates were 97% and 70% for RO5 and Pb2+, respectively. The adsorption mechanism was explored by means of the IR spectrum and the UV-vis diffuse reflection spectrum (DRS) together with theoretical calculations. The adsorption of dyes was mainly driven by the strong interaction between dye molecules and the hydrophobic cavity of CB[8], and the Pb2+ adsorption was mainly driven by the coordination of Pb2+ with the carbonyl of the CB[8] port and the amino group of chitosan. The ultrahigh adsorption capacity allows the use of CB[8]-CS as potential adsorbent for the simultaneous removal of heavy metal ions and organic dyes from aqueous solution.

Proprotein convertase subtilisin/kexin type 6 promotes in vitro proliferation, migration and inflammatory cytokine secretion of synovial fibroblast­like cells from rheumatoid arthritis via nuclear­κB, signal transducer and activator of transcription 3 and extracellular signal regulated 1/2 pathways.

Our previous studies demonstrated that expression of proprotein convertase subtilisin/kexin type 6 (PCSK6) is greatly enhanced in rheumatoid arthritis fibroblast­like synoviocytes (RASFs), and that PCSK6 inhibition decreases cell proliferation, migration and invasion. The present study aimed to investigate the functional role of PCSK6 in the hyperplasia of RASFs. Cultured RASFs from RA patients were stimulated with recombinant human (rh)PCSK6. Subsequent changes in proliferation, invasion, migration and the secretion of inflammatory cytokines were measured in vitro using MTT, wound healing and Transwell assays, and ELISA. Cell cycle and apoptosis were analyzed by flow cytometry. Influence on downstream gene expression levels were analyzed using reverse transcription­quantitative polymerase chain reaction. Specific signaling pathways responsible for these effects were analyzed using western blotting and confirmed with pathway­specific inhibitors. It was demonstrated that rhPCSK6 significantly increased RASF cell invasion, migration and proliferation, which was influenced through both reduced cell cycle arrest and reduced apoptosis. Furthermore, rhPCSK6 stimulated RASFs to secrete the inflammatory cytokines interleukin (IL)­1α, IL­1ß and IL­6, and exhibit altered expression of genes involved in angiogenesis, hypoxia, proliferation and inflammation. These cellular effects were mediated via the nuclear factor (NF)­κB, signal transducer and activator of transcription 3 (STAT3) and extracellular signal regulated (ERK)1/2 signaling pathways. The results demonstrated that signaling via NF­κB and STAT3 mediated cell cycle arrest, and signaling through NF­κB mediated apoptosis in RASF cells stimulated with PCSK6. PCSK6 can activate NF­κB, STAT3 and ERK1/2 signaling pathways in vitro to enhance cell proliferation, migration, invasion and inflammation in RASF cells. These findings suggest that PCSK6 may be an important therapeutic target in RA.

Inhibition of furin results in increased growth, invasiveness and cytokine production of synoviocytes from patients with rheumatoid arthritis.

OBJECTIVES: Fibroblast-like synoviocytes derived from patients with rheumatoid arthritis play a key role by local production of cytokines and proteolytic enzymes that degrade the extracellular matrix and cartilage. These synoviocytes acquire phenotypic characteristics commonly observed in transformed cells, like anchorage-independent growth, increased proliferation and invasiveness, and insensitivity to apoptosis. Furin is a ubiquitous proprotein convertase that is capable of cleaving precursors of a wide variety of proteins. In patients with rheumatoid arthritis, furin is reported to be highly expressed in the synovial pannus compared with healthy persons. However, the mechanisms are poorly understood. This study is to explore the effect of furin overexpression in rheumatoid synoviocytes. METHODS: In this study, RNA interference was used to knock down furin expression and to assess the resultant effects on biological behaviors of synoviocytes, such as cell proliferation, invasion, migration, cell cycle and cell apoptosis. In addition, the production of inflammatory cytokines was evaluated. RESULTS: The results showed that the inhibition of furin enhanced proliferation, invasion, and migration of synoviocytes in vitro. Cell cycle was accelerated and cell death was affected by furin knockdown. Also, the inhibition of furin increased interleukin-1ß and tumor necrosis factor-α secretion of synoviocytes. CONCLUSIONS: Inhibition of furin enhances invasive phenotype of synoviocytes from patients with rheumatoid arthritis, implying a protective role of furin. Agents targeting upregulation of furin may have therapeutic potential for rheumatoid arthritis.

Inhibition of pro-protein convertase subtilisin/kexin type 6 has a protective role against synovitis in a rat model of rheumatoid arthritis.

The aim of the present study was to assess the effects of pro-protein convertase subtilisin/kexin type 6 (PCSK6), a proteinase implicated in the proteolytic activity of various precursor proteins and involved in the regulation of protein maturation, in fibroblast­like synoviocytes (FLS) of a rat model of collagen­induced arthritis (CIA). Cultured FLS from CIA models were subjected to small interfering RNA mediated PCSK6 knockdown, followed by assessment of the proliferation, invasive and migratory capacity, the secretion of inflammation factors and the cell cycle. Expression of genes associated with proliferation, invasion, migration and inflammation was detected by reverse transcription polymerase chain reaction. The results showed that PCSK6 knockdown significantly decreased the cell proliferation, invasion and migration of FLS from rats with CIA. ELISA showed an obvious decrease of tumor necrosis factor α and interleukin 1ß secretion, and flow cytometric analysis revealed G0/G1 arrest of FLS following PCSK6 knockdown. Furthermore, a decrease in the mRNA levels of inflammation­associated chemokine CXCL9, angiogenesis­associated genes MMP­2, MMP­9 and NOSTRIN, hypoxia­associated gene HIF­1α, adhesion­associated gene MPZL2, proliferation­associated gene IGF­2 and citrullination­associated gene PADI4 was detected after PCSK6 knockdown. The results of the present study indicated that inhibition of PCSK6 may have a protective role against synovitis in rheumatoid arthritis.

Inhibition of PCSK6 may play a protective role in the development of rheumatoid arthritis.

OBJECTIVE: To assess the effect of proprotein convertase subtilisin/kexin type 6 (PCSK6) in the synovial fibroblasts of rheumatoid arthritis (RA). PCSK6 is a proteinase implicated in the proteolytic activity of various precursor proteins and involved in the regulation of protein maturation. METHODS: PCSK6 expression was detected in the synovial tissue of 10 patients with RA, 10 controls with osteoarthritis, and 10 controls with ankylosing spondylitis using Western blotting and quantitative real-time PCR. Genotyping of 67 tag single-nucleotide polymorphisms (SNP) was performed using an Illumina VeraCode (Illumina) microarray in a case-control study including 267 patients with RA and 160 healthy controls. Genotyping of 4 other tag SNP was performed using a TaqMan probe genotyping assay in 1056 healthy controls and 1151 patients with RA. Cultured RA synovial fibroblasts (RASF) were transfected with PCSK6 small interfering RNA to study changes in the proliferation, invasion, migration capacity, secretion of inflammatory cytokines, cell cycle, and expression profiles of the RASF. RESULTS: Expression of PCSK6 mRNA and protein was significantly higher in the synovial tissues of individuals with RA than in control tissues. One SNP, rs8029797, was significantly associated with RA (p = 0.011). Knockdown of PCSK6 by RNA interference significantly decreased proliferation, invasion, and migration of RASF. These changes in RASF appeared to be related to reduced tumor necrosis factor-α secretion, G0/G1 arrest, and altered expression of various proteins including those involved in angiogenesis (matrix metalloproteinase 9, nitric oxide synthase trafficking), hypoxia (hypoxia-inducible factor-α, thioredoxin domain containing 5), proliferation (chromosome 10 open reading frame 116), and inflammation [CCL7, chemokine (C-X-C motif) ligand 9, interleukin 26]. CONCLUSION: PCSK6 is upregulated in the synovial tissues of patients with RA and has a genetic effect on the risk of RA. Inhibition of PCSK6 may play a protective role in the development of RA.