Emerging biologic frontiers for Sjogren's syndrome: Unveiling novel approaches with emphasis on extra glandular pathology.

Primary Sjögren's Syndrome (pSS) is a complex autoimmune disorder characterized by exocrine gland dysfunction, leading to dry eyes and mouth. Despite growing interest in biologic therapies for pSS, FDA approval has proven challenging due to trial complications. This review addresses the absence of a molecular-target-based approach to biologic therapy development and highlights novel research on drug targets and clinical trials. A literature search identified potential pSS treatment targets and recent advances in molecular understanding. Overlooking extraglandular symptoms like fatigue and depression is a notable gap in trials. Emerging biologic agents targeting cytokines, signal pathways, and immune responses have proven efficacy. These novel therapies could complement existing methods for symptom alleviation. Improved grading systems accounting for extraglandular symptoms are needed. The future of pSS treatment may involve gene, stem-cell, and tissue-engineering therapies. This narrative review offers insights into advancing pSS management through innovative biologic interventions.

Proteomics Sequencing Reveals the Role of TGF-ß Signaling Pathway in the Peripheral Blood of Offspring Rats Exposed to Fluoride.

The underlying mechanism of fluorosis has not been fully elucidated. The purpose of this study was to explore the mechanism of fluorosis induced by sodium fluoride (NaF) using proteomics. Six offspring rats exposed to fluoride without dental fluorosis were defined as group A, 8 offspring rats without fluoride exposure were defined as control group B, and 6 offspring rats exposed to fluoride with dental fluorosis were defined as group C. Total proteins from the peripheral blood were extracted and then separated using liquid chromatography-tandem mass spectrometry. The identified criteria for differentially expressed proteins were fold change > 1.2 or < 0.83 and P < 0.05. Gene Ontology function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the oeCloud tool. The 177 upregulated and 22 downregulated proteins were identified in the A + C vs. B group. KEGG pathway enrichment analysis revealed that transforming growth factor-ß (TGF-ß) signaling pathway significantly enriched. PPI network constructed using Cytoscape confirmed RhoA may play a crucial role. The KEGG results of genes associated with fluoride and genes associated with both fluoride and inflammation in the GeneCards database also showed that TGF-ß signaling pathway was significantly enriched. The immunofluorescence in HPA database showed that the main expression sites of RhoA are plasma membrane and cytosol, while the main expression site of Fbn1 is the Golgi apparatus. In conclusion, long-term NaF intake may cause inflammatory response in the peripheral blood of rats by upregulating TGF-ß signaling pathway, in which RhoA may play a key role.

Reaction mode between Si and Fe and evaluation of optimal species in poly-silicic-ferric coagulant.

A kind of Fe-polysilicate polymer, poly-silicic-ferric (PSF) coagulant was prepared by co-polymerization (hydroxylation of mixture of Fe3+ and fresh polysilicic acid (PS)), in which PSF0.5, PSF1 or PSF3 denotes Si/Fe molar ratio of 0.5, 1 or 3, respectively. The effects of Si/Fe ratio and reaction time (co-polymerization time or aging time) on the reaction mode between Si and Fe were studies, and the optimal species of PSF was evaluated by pH change during the preparation of PSF and coagulation tests. The results showed that the characteristics of PSF are largely affected by both reaction time and Si/Fe ratio. PSF is found to be a essential complex of Si, Fe, and many other ions. The reaction mode between Si and Fe differs with various Si/Fe ratios. The pH of PSF0.5, PSF1 or PSF3 tended to be stable when reaction time is 10, 25 or 55 min, respectively, which is almost consistent with the time reaching the relative stable morphology that is just the optimal species of higher coagulation efficiency. The optimal reaction time reaching optimal species can be evaluated by measuring the pH change during the polymerization process.

Role of extracellular exopolymers on biological phosphorus removal.

Three sequencing batch reactors supplied with different carbon sources were investigated. The system supplied with glucose gained the best enhanced biological phosphorus removal although all of the three reactors were seeded from the same sludge. With the measurement of poly-beta-hydroxyalkanoate (PHA) concentration, phosphorus content in sludge and extracellular exopolymers (EPS) with scanning electron microscopy (SEM) combined with energy dispersive spectrometry (EDS), it was found that the biosorption effect of EPS played an important role in phosphorus removal and that the amount of PHA at the end of anaerobic phase was not the only key factor to determine the following phosphorus removal efficiency.

Flux enhancement during ultrafiltration of produced water using turbulence promoter.

Concentration polarization and membrane fouling remain one of the major hurdles for the implementation of ultrafiltration of produced water. Although many applications for ultrafiltration were already suggested, only few were implemented on an industrial scale. Among those techniques, turbulence promoter can be more simple and effective in overcoming membrane fouling and enhancing membrane flux. As for the result that turbulence promoter increase fluid velocity, wall shear rates and produce secondary flows or instabilities, the influence of turbulence promoter was investigated on permeate flux during produced water ultrafiltration and the potential application of this arrangement for an industrial development. Experimental investigations were performed on 100 KDa molecular weight cut-off PVDF single-channel tubular membrane module using four kinds of turbulence promoters. It is observed that the significant flux enhancement in the range of 83%-164% was achieved while the hydraulic dissipated power per unit volume of permeate decreased from 31%-42%, which indicated that the using of turbulence promoter is more efficient than operation without the turbulence promoter. The effects of transmembrane pressure and cross-flow velocity with and without turbulence promoter were studied as well. Among the four kinds of turbulence promoters, winding inserts with 20.0 mm pitch and 1.0 mm wire diameter showed better performances than the others did.

Effect of components in activated sludge liquor on membrane fouling in a submerged membrane bioreactor.

By a membrane bioreactor with a settle tank in long-term operation and batch experiments, the effects of flocs, soluble microorganism products (SMPs) and metal ions in activated sludge liquor on membrane fouling were investigated. The results showed that foulants absorbed each other and formed a fouling layer as a "second membrane" influencing the permeability of the membrane. The "gel layer" caused by SMPs and "cake layer" by flocs showed great differences in morphology by analysis of scanning electron microscope and atomic force microscope. The "gel layer" was more compact and of poor permeability. When the membrane flux was 40 L/(m(2) x h), the rate of membrane fouling caused by supernatant (0.011 MPa/h) was greater than that by sludge liquor (0.0063 MPa/h). SMPs played very important roles on membrane fouling. In the bulking sludge, with SMPs increasing, the rate of membrane fouling (0.0132 MPa/h) was faster. While after flocculation of the SMPs, the rate of fouling decreased to 0.0034 MPa/h. Flocs could keep holes in their overlaps. They could alleviate membrane fouling by preventing the SMPs directly attaching on membrane surface.

Micelles based on methoxy poly(ethylene glycol)-cholesterol conjugate for controlled and targeted drug delivery of a poorly water soluble drug.

In this study, quercetin (QC) with cancer chemoprevention effect and anticancer potential was loaded into polymeric micelles of methoxy poly(ethylene glycol)-cholesterol conjugate (mPEG-Chol) in order to increase its water solubility. MPEG-Chol with lower critical micelle concentration (CMC) value (4.0 x 10(-7) M - 13 x 10(-7) M) was firstly synthesized involving two steps of chemical modification on cholesterol by esterification, and then QC was incorporated into mPEG-Chol micelles by self-assembly method. After the process parameters were optimized, QC-loaded micelles had higher drug loading (3.66%) and entrapment efficiency (93.51%) and nano-sized diameter (116 nm). DSC analysis demonstrated that QC had been incorporated non-covalently into the micelles and existed as an amorphous state or a solid solution in the polymeric matrix. The freeze-dried formulation with addition of 1% (w/v) mannitol as cryoprotectant was successfully developed for the long-term storage of QC-loaded micelles. Compared to free QC, QC-loaded micelles could release QC more slowly. Moreover, the release of QC from micelles was slightly faster in PBS at pH 5 than that in PBS at pH 7.4, which implied that QC-loaded micelles might be pH-sensitive and thereby selectively deliver QC to tumor tissue with unwanted side effects. Therefore, mPEG-Chol was a promising micellar vector for the controlled and targeted drug delivery of QC to tumor and QC-loaded micelles were also worth being further investigated as a potential formulation for cancer chemoprevention and treatment.

Development of glycyrrhetinic acid-modified stealth cationic liposomes for gene delivery.

The glycyrrhetinic acid-modified stealth cationic liposomes (GA-PEG-CLs) loaded with pDNA (GA-PEG-CLPs) were developed and found to transfect human hepatocellular carcinoma cell line HepG2 with high efficiency. GA-PEG-CLs were comprised of DOTAP, cholesterol (Chol) and glycyrrhetinic acid-polyethyleneglycol-cholesterol conjugate (GA-PEG-Chol). Agarose gel electrophoresis revealed that 5% GA-PEG-CLs constituted by DOTAP/Chol/GA-PEG-Chol at molar ratio of 50:45:5 could completely entrap pDNA at a lower liposomes/pDNA weight ratios of 4:1 (N/P ratio: 1.14). Compared to ordinary cationic liposomes (CLs), steric cationic liposomes (PEG-CLs) and 1% GA-PEG-CLs made from DOTAP/Chol/MPEG2000-Chol/GA-PEG-Chol at molar ratio of 50:45:4:1, 5% GA-PEG-CLs were found to possess the highest transfection efficiency as gene vectors in serum-free or serum-containing medium in PKCalpha over-expressed HepG2 cells but no significance difference in human embryonic kidney cell line HEK 293. Additionally, 5% GA-PEG-CLs have the lowest cytotoxicity on human normal hepatocyte cell line L02. The competitive inhibition experiments mediated by GA were carried out in HepG2 cells, which demonstrated that GA-PEG-CLs could deliver selectively pDNA to hepatoma cells by the targeting moiety GA. In conclusion, GA-PEG-CLs containing 5% GA-PEG-Chol might be one of the most potential gene vectors as hepatoma targeting therapy.

Development of PLGA nanoparticles simultaneously loaded with vincristine and verapamil for treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the malignant tumors with poor chemo-sensitivity to vincristine sulfate (VCR) due to multi-drug resistance (MDR). Combinations of encapsulated VCR and verapamil hydrochloride (VRP, a chemo-sensitizer) might be a potential strategy to improve HCC therapeutic efficacy of VCR. PLGA nanoparticles (PLGANPs) simultaneously loaded with VCR and VRP (CVn) were prepared. The entrapment efficiencies of VCR and VRP were 70.92 ± 3.78% and 85.78 ± 3.23%, respectively (n = 3). The HCC therapeutic activity of CVn was assessed using MTT assay. In BEL7402 and BEL7402/5-FU human hepatocarcinoma cell lines, CVn had the same antitumor effect as one free drug/another agent-loaded PLGANPs (C + Vn or Cn + V) combination and coadministration of two single-agent-loaded PLGANPs (Cn + Vn), which was slightly higher than that of the free VCR/VRP combination (C - V). CVn might cause lower normal tissue drug toxicity by the enhanced permeation and retention effect in vivo. Additionally, CVn might cause fewer drug-drug interaction and be the most potential formulation to simultaneously deliver VCR and VRP to the target cell in vivo than the other three nanoparticle formulations (C + Vn, Cn + V, and Cn + Vn). Therefore, we speculate that CVn might be the most effective preparation in the treatment of drug-resistant human HCC in vivo.

Comparative performance between intermittently cyclic activated sludge-membrane bioreactor and anoxic/aerobic-membrane bioreactor.

A process of intermittently cyclic activated sludge-membrane bioreactor (ICAS-MBR) was developed to enhance the performance of biological phosphorus removal (EBPR), which was constructed under sequencing anoxic/anaerobic/aerobic condition. The performance between ICAS-MBR and conventional anoxic/aerobic-membrane bioreactor (A/O-MBR) in terms of phosphorus removal, nitrification performance and microbial aspects were investigated in this study. The experimental results indicated that the phosphorus removal efficiency in ICAS-MBR process increased from 65% to 83% when compared with A/O-MBR. It was also found that the COD removal efficiencies of the two processes were over 94%, and NH(4)(+)-N and TN average removal efficiencies were 96% and 69% in ICAS-MBR and 96% and 78% in A/O-MBR, respectively. Furthermore, micrographs observation obtained confirmed the succession and diversification of microorganisms in the two systems followed a similar regularity.

[Quantitative investigation on flocculation and destruction of poly-silicic-ferric (PSF) coagulant].

An inorganic polymer, poly-silicic-ferric (PSF) coagulant was prepared using water glass, FeSO4 x 7H2O and NaClO3 by copolymerization. A comparison of coagulation performance, distribution of residual flocs in finished water and influence of turbulent shear force on the flocs between PSF and polyferric aluminum (PFA) was explored by jar tests and particle counter approach. The results indicate that PSF has superior removal of COD at higher dose to PFA. Flocculating speed should not be much higher or lower when using PSF as coagulant in treating surface water, and excellent coagulation efficiency can be obtained by the close cooperation of flocculation speed with flocculation time, that is, higher flocculation speed should be consistent with shorter flocculation time. The PFA flocs are much easier destructed than PSF flocs when increasing the turbulent shear force, and the destructed PSF flocs tend to be more easily re-coupled than PFA flocs. From the order magnitude, the flocculation coefficient KA of PSF is from 10(-2) to 10(-3), in comparison with the destruction coefficient KB from 10(-7) to 10(-8). For particles whose size is smaller than 2 microm, KA of PSF is 4 order magnitude more than that of PFA, and KB of PSF is almost the same to that of PFA; while for the other particles, KA of PSF is 2 order magnitude more than that of PFA, and KB of PSF is almost ten times smaller than that of PFA.

[Analysis of reaction process between Si and Fe in poly-silicic-ferric sulfate (PSF) coagulant].

A new inorganic polymer coagulant, poly-silic-ferric sulfate (PSF) with various Si/Fe ratios (PSF0.5, PSF1 and PSF denote Si/Fe molar ratios of 0.5, 1 and 3, respectively), was prepared using water glass, ferrous sulfate and sodium chlorate by co-polymerization, and pH value was measured during the preparation process. The influence of both Si/Fe ratio and reaction time (polymerization time) on the complexation process (bonding mode) between Si and Fe was explored with many analytical methods (such as X-ray diffraction (XRD), ultraviolet/visible absorption (UVA) scanning, transmission electron microscope (TEM), photon correlation spectra (PCS) and infrared spectrum (IR) using PSF samples taken from different reaction time at different Si/Fe ratios. The results show that the characteristics of PSF are largely influenced by both reaction time and Si/Fe ratios. PSF is found to be a complexation compound of Si, Fe and many other ions, instead of a simple mixture of raw materials. The complexation process between Si and Fe may be different from various Si/Fe ratios, namely, the bonding rate, bonding mode and the stability of the bond between Si and Fe are different from various Si/Fe ratios: the polymer based on Si-O-Fe-O-Fe-O-Si bond may be formed at low Si/Fe ratio, in comparison with that based on Si-O-Fe-O-Si-O-Si bond at high Si/Fe ratio; the formation rate of Fe-O-Fe bond is rapid and there may be a mutual acceleration between Fe-O-Fe bond and Si-O-Fe bond, while the formation rate of Si-O-Si is slow and maybe there is a mutual retardation between Si-O-Fe bond and Si-O-Si bond; the stability of Fe-O-Fe bond is weaker than that of Si-O-Fe or Si-O-Si bond.

[Research of performances for the organic membrane modified by inorganic material].

Nano-sized alumina particles as inorganic additive were dispersed in the poly (vinylidene fluoride) uniformly to prepare organic-inorganic composite membranes. Contact angle between water and the membrane surface were measured by contact angle measurement in order to characterize the hydrophilicity changing of the membrane surface. The membrane surface structures, porous distribution on the membrane surface, the cross-sectional structures and nanometer particles distribution were examined by confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) respectively. Membrane properties were characterized by ultrafiltration (UF) experiments in terms of water flux and antifouling properties. Membranes mechanical performances were measured by omnipotence electronic intensity measuring instrument (W-56). Experiments indicate that Al2 O3 -PVDF composite membranes exhibit significant differences in surface hydrophilicity properties, flux, and intensity and antifouling performances due to nano-sized particles addition.

[Analysis of solid-liquid oxidizing poly silicic ferric sulfate (PSF-I)].

A new type of inorganic coagulant, solid-liquid oxidative poly silicic ferric sulfate (PSF-I), was prepared by adding KMnO4 and stabilizer M to poly silicic ferric sulfate (PSF). The species characteristics of PSF-I, the filtrate of PSF-I and PSF with spectrophotometer, and coagulation performance of PSF-I and the filtrate of PSF-I with jar tests were explored, respectively. Coagulation efficiency of PSF-I was studied compared to that of PSF and poly ferric sulfate (PFS), and the effect of storage time on coagulation performance of PSF-I was investigated. The results show that KMnO4 added to PSF modifies the microstructure of PSF, increasing species size of PSF and making UVA characteristic peaks of Fe3+ ion in PSF-I higher than that in PSF. There exists KMnO4 unattached in PSF-I. The solid phase in PSF-I is a kind of primary nucleus for building up flocs. The optimal dosage with PSF-I is 9 mg x L(-1), in comparison with 12 mg x L(-1) by PSF-I filtrate. The removal of natural organic matters (NOM) is not only caused by adsorption/charge-neutralization and co-precipitation but also by oxidization using PSF-I as coagulant, while to PSF and PFS, adsorption/charge-neutralization and co-precipitation is the only coagulation mechanism.