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The modern Gastroenterology have witnessed an essential stride since Helicobacter pylori was first found in the stomach and then its pathogenic effect was discovered. According to the researches conducted during the nearly 40 years, it has been found that this bacterium is associated with a natural history of many upper gastrointestinal diseases. Epidemiological data show an increased incidence of autoimmune disorders with or after infection with specific microorganisms. The researches have revealed that H. pylori is a potential trigger of gastric autoimmunity, and it may be associated with other autoimmune diseases, both innate and acquired. This paper reviews the current support or opposition about H. pylori as the role of potential triggers of autoimmune diseases, including inflammatory bowel disease, autoimmune thyroiditis, type 1 diabetes mellitus, autoimmune liver diseases, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, as well as Sjogren’s syndrome, chronic urticaria and psoriasis, and tried to explain the possible mechanisms.

The gene AtCSR encodes peptidyl-prolyl cis/trans isomerases （PPIases） that accelerate energetically unfavorable cis/trans isomerization of the peptide bond preceding proline production.In our studies,we found that AtCSR was associated with cadmium （Cd）-sensitive response in Arabidopsis.Our results show that AtCSR expression was triggered by Cd-stress in wild type Arabidopsis.The expression of some genes responsible for Cd2＋ transportation into vacuoles was induced,and the expression of the iron-regulated transporter 1 （IRT1） related to Cd2＋ absorption from the environment was not induced in wild type with Cd2＋ treatment.The expression of Cd-transportation related genes was not in response to Cd-stress,whereas IRT expression increased dramatically in atcsr-2 with Cd2＋ treatment.The expression of glutathione 1 （GSH1） was consistent with GSH being much lower in atcsr-2 in comparison with the wild type with Cd2＋ treatment.Additionally,malondialdehyde （MDA）,hydrogen peroxide,and Cd2＋ contents,and activities of some antioxidative enzymes,differed between the wild type and atcsr-2.Hydrogen sulfide （H2S） has been confirmed as the third gas-transmitter over recent years.The findings revealed that the expression pattern of H2 S-releasing related genes and that of Cd-induced chelation and transportation genes matched well in the wild type and atcsr-2,and H2S could regulate the expression of the Cd-induced genes and alleviate Cd-triggered toxicity.Finally,one possible suggestion was given：down-regulation of atcsr-2,depending on H2S gas-transmitter not only weakened Cd2＋ chelation,but also reduced Cd2＋ transportation into vacuoles,as well as enhancing the Cd2＋ assimilation,thus rendering atcsr-2 mutant sensitive to Cd-stress.

ObjectivesDysregulated chondrocyte metabolism is closely associated with the pathogenesis of osteoarthritis (OA). Suppressing chondrocyte catabolism to restore cartilage homeostasis has been extensively explored, whereas far less effort has been invested toward enhancing chondrocyte anabolism. This study aimed to repurpose clinically approved drugs as potential stimulators of chondrocyte anabolism in treating OA.MethodsScreening of a Food and Drug Administration-approved drug library; Assays for examining the chondroprotective effects of digoxin in vitro; Assays for defining the therapeutic effects of digoxin using a surgically-induced OA model; A propensity-score matched cohort study using The Health Improvement Network to examine the relationship between digoxin use and the risk of joint OA-associated replacement among patients with atrial fibrillation; identification and characterisation of the binding of digoxin to low-density lipoprotein receptor-related protein 4 (LRP4); various assays, including use of CRISPR-Cas9 genome editing to delete LRP4 in human chondrocytes, for examining the dependence on LRP4 of digoxin regulation of chondrocytes.ResultsSerial screenings led to the identification of ouabain and digoxin as stimulators of chondrocyte differentiation and anabolism. Ouabain and digoxin protected against OA and relieved OA-associated pain. The cohort study of 56 794 patients revealed that digoxin use was associated with reduced risk of OA-associated joint replacement. LRP4 was isolated as a novel target of digoxin, and deletion of LRP4 abolished digoxin’s regulations of chondrocytes.ConclusionsThese findings not only provide new insights into the understanding of digoxin’s chondroprotective action and underlying mechanisms, but also present new evidence for repurposing digoxin for OA.

Chemotherapy drugs are mainly administered via intravenous injection or oral administration in a very a high dosage. If there is a targeted drug vehicle which can be deployed on the tumor, the medical treatment is specific and precise. Binary mixing of biocompatible Pluronic® F127 and Pluronic® L121 was used in this study for a drug carrier of pluronic biomedical hydrogels (PBHs). Based on the same PBH ingredients, the addition of fluorouracil (5-FU) was separated in three ways when it was incorporated with pluronics: F127-L121-(5-FU), F127-(5-FU), and L121-(5-FU). Small angle X-ray scattering experiments were performed to uncover the self-assembled structures of the PBHs. Meanwhile, the expected micelle and lamellar structural changes affected by the distribution of 5-FU were discussed with respect to the corresponding drug release monitoring. PBH-all with the mixing method of F127-L121-(5-FU) has the fastest drug release rate owing to the undulated amphiphilic boundary. In contrast, PBH-2 with the mixing method of L121-(5-FU) has a prolonged drug release rate at 67% for one month of the continuous drug release experiment because the flat lamellar amphiphilic boundary of PBH-2 drags the migration of 5-FU from the hydrophobic core. Therefore, the PBHs developed in the study possess great potential for targeted delivery and successfully served as a microenvironment model to elucidate the diffusion pathway of 5-FU.

Stem cell therapy holds great promise for future clinical practice for treatment of advanced liver diseases. However, the fate of stem cells after transplantation, including the distribution, viability, and the cell clearance, has not been fully elucidated. Herein, recent advances regarding the imaging tools for stem cells tracking mainly in chronic liver diseases with the advantages and disadvantages of each approach have been described. Magnetic resonance imaging is a promising clinical imaging modality due to non-radioactivity, excellent penetrability, and high spatial resolution. Fluorescence imaging and radionuclide imaging demonstrate relatively increased sensitivity, with the latter excelling in real-time monitoring. Reporter genes specialize in long-term tracing. Nevertheless, the disadvantages of low sensitivity, radiation, exogenous gene risk are inevitably present in each of these means, respectively. In this review, we aim to comprehensively evaluate the current state of methods for tracking of stem cell, highlighting their strengths and weaknesses, and providing insights into their future potential. Multimodality imaging strategies may overcome the inherent limitations of single-modality imaging by combining the strengths of different imaging techniques to provide more comprehensive information in the clinical setting.

The gene AtCSR encodes peptidyl-prolyl cis/trans isomerases (PPIases) that accelerate energetically unfavorable cis/trans isomerization of the peptide bond preceding proline production. In our studies, we found that AtCSR was associated with cadmium (Cd)-sensitive response in Arabidopsis . Our results show that AtCSR expression was triggered by Cd-stress in wild type Arabidopsis . The expression of some genes responsible for Cd 2+ transportation into vacuoles was induced, and the expression of the iron-regulated transporter 1 ( IRT1 ) related to Cd 2+ absorption from the environment was not induced in wild type with Cd 2+ treatment. The expression of Cd-transportation related genes was not in response to Cd-stress, whereas IRT expression increased dramatically in atcsr-2 with Cd 2+ treatment. The expression of glutathione 1 ( GSH1 ) was consistent with GSH being much lower in atcsr-2 in comparison with the wild type with Cd 2+ treatment. Additionally, malondialdehyde (MDA), hydrogen peroxide, and Cd 2+ contents, and activities of some antioxidative enzymes, differed between the wild type and atcsr-2 . Hydrogen sulfide (H 2 S) has been confirmed as the third gas-transmitter over recent years. The findings revealed that the expression pattern of H 2 S-releasing related genes and that of Cd-induced chelation and transportation genes matched well in the wild type and atcsr-2 , and H 2 S could regulate the expression of the Cd-induced genes and alleviate Cd-triggered toxicity. Finally, one possible suggestion was given: down-regulation of atcsr-2 , depending on H 2 S gas-transmitter not only weakened Cd 2+ chelation, but also reduced Cd 2+ transportation into vacuoles, as well as enhancing the Cd 2+ assimilation, thus rendering atcsr-2 mutant sensitive to Cd-stress.

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline “2018 Standard Edition”. However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons’ surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons’ skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Atherosclerosis (AS) is a chronic inflammatory disorder characterized by foam cell formation and persistent inflammation as central pathological drivers. Although colchicine (Col) exhibits potent anti-inflammatory activities, its clinical application is limited by a narrow therapeutic window. In the present study, we developed phosphatidylserine-exposing nanovesicles (Col@PSVs) that leverage the innate phagocytic capacity of macrophage-derived foam cells by presenting surface \"eat-me\" signals, thereby enabling targeted immune modulation. The synergistic collaboration between Col and PSVs allows low-dose Col to retain robust anti-inflammatory efficacy while mitigating dose-dependent toxicity. Mechanistically, Col@PSVs potently suppress CCR7-mediated NF-κB signaling activation in foam cells, leading to a marked downregulation of pro-inflammatory cytokine and disruption of inflammatory cascades. In ApoE AS mouse models, Col@PSVs treatment significantly improved plaque stability and attenuated disease progression. These findings highlight the pivotal role of the CCR7/NF-κB signaling pathway in AS-associated inflammation and present a translational nanotherapeutic strategy with the potential to overcome the clinical limitations of Col.

In this study, copper oxide nanoparticles (CuO NPs) were green synthesized using the leaf extract of Momordica cochinchinensis (Lour.). Various characterization techniques such as Energy-dispersive x-ray spectroscopy (EDS), Ultraviolet Visible (UV-vis) Spectroscopy, x-ray diffraction (XRD), Transmission Electron Microscopy (TEM) and Fourier-transform Infrared (FTIR) Spectroscopy were utilized to study the formation of CuO NPs. DLS and TEM analysis revealed the formation of sphere-shaped CuO NPs with mean particle size of 56 nm. Additionally, the prepared CuO NPs were incubated with Hepatic (HepG2) cells to check their cel viability and evaluate the formation of reactive oxygen species (ROS). The results of the current work exhibited a concentration-dependent decline in the viability of HepG2 cells with half maximal inhibitory concentration (IC50) value of 75 g ml−1. The cytotoxic effect of CuO NPs was responsible for the cell apoptosis as well as ROS induction in the HepG2 cells. Further, the prepared CuO NPs could act as possible chemotherapeutic agent for the treatment of liver hepatocellular carcinoma (HCC) in future.

It has long been assumed that most parts of a genome and most genetic variations or SNPs are non-functional with regard to reproductive fitness. However, the collective effects of SNPs have yet to be examined by experimental science. We here de- veloped a novel approach to examine the relationship between traits and the total amount of SNPs in panels of genetic refer- ence populations. We identified the minor alleles （MAs） in each panel and the MA content （MAC） that each inbred strain car- ried for a set of SNPs with genotypes determined in these panels. MAC was nearly linearly linked to quantitative variations in numerous traits in model organisms, including life span, tumor susceptibility, learning and memory, sensitivity to alcohol and anti-psychotic drugs, and two correlated traits poor reproductive fitness and strong immunity. These results suggest that the collective effects of SNPs are functional and do affect reproductive fitness.