Interplay between COVID-19 and Secukinumab treatment in Spondylarthritis patients during the omicron surge: a retrospective cohort study.

The objective of this retrospective cohort study was to assess the relationship between Corona Disease 2019 (COVID-19) and Secukinumab treatment in patients with Spondylarthritis (SpA) in China during the omicron surge. Researchers retrieved 1018 medical records of Secukinumab-treated patients between January 2020 and January 2023 from the West China Hospital of Sichuan University. Out of these, 190 SpA patients from the rheumatology clinic were selected for the study. Guided phone questionnaires were administered by research staff to collect baseline characteristics, SpA disease status, and COVID-19 clinical outcomes. Cohabitants served as the control group and provided COVID-19 related data. Of the 190 potential SpA patients, 122 (66%) completed the questionnaire via phone, along with 259 cohabitants. 84.4% of SpA patients were diagnosed with Ankylosing Spondylitis (AS), and 15.6% were diagnosed with Psoriatic Arthritis (PsA). The rate of SARS-CoV-2 infection was 83.6% in the Secukinumab group and 88.8% in the cohabitants control group, with no significant difference (OR = 0.684, CI 0.366-1.275). One instance of severe COVID-19 was observed in the Secukinumab group, while two were identified in the cohabitants control group. Patients in the Secukinumab group had less time with fever caused by COVID-19 (p = 0.004). Discontinuing Secukinumab after SARS-CoV-2 infection did not significantly affect the course of COVID-19 or worsen SpA status according to our data. Our study suggests that administering Secukinumab to SpA patients does not increase their susceptibility to contracting SARS-CoV-2, and may have a positive effect on the course of SARS-CoV-2 infection.

Advances in mesenchymal stem cell-derived extracellular vesicles therapy for Sjogren's syndrome-related dry eye disease.

Sjogren's syndrome (SS) is a chronic autoimmune disorder that affects exocrine glands, particularly lacrimal glands, leading to dry eye disease (DED). DED is a common ocular surface disease that affects millions of people worldwide, causing discomfort, visual impairment, and even blindness in severe cases. However, there is no definitive cure for DED, and existing treatments primarily relieve symptoms. Consequently, there is an urgent need for innovative therapeutic strategies based on the pathophysiology of DED. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic tool for various autoimmune disorders, including SS-related DED (SS-DED). A particularly intriguing facet of MSCs is their ability to produce extracellular vesicles (EVs), which contain various bioactive components such as proteins, lipids, and nucleic acids. These molecules play a key role in facilitating communication between cells and modulating a wide range of biological processes. Importantly, MSC-derived EVs (MSC-EVs) have therapeutic properties similar to those of their parent cells, including immunomodulatory, anti-inflammatory, and regenerative properties. In addition, MSC-EVs offer several notable advantages over intact MSCs, including lower immunogenicity, reduced risk of tumorigenicity, and greater convenience in terms of storage and transport. In this review, we elucidate the underlying mechanisms of SS-DED and discuss the relevant mechanisms and targets of MSC-EVs in treating SS-DED. In addition, we comprehensively review the broader landscape of EV application in autoimmune and corneal diseases. This review focuses on the efficacy of MSC-EVs in treating SS-DED, a field of study that holds considerable appeal due to its multifaceted regulation of immune responses and regenerative functions.

Montmorillonite Membranes with Tunable Ion Transport by Controlling Interlayer Spacing.

Membranes incorporating two-dimensional (2D) materials have shown great potential for water purification and energy storage and conversion applications. Their ordered interlayer galleries can be modified for their tunable chemical and structural properties. Montmorillonite (MMT) is an earth-abundant phyllosilicate mineral that can be exfoliated into 2D flakes and reassembled into membranes. However, the poor water stability and random interlayer spacing of MMT caused by weak interlamellar interactions pose challenges for practical membrane applications. Herein, we demonstrate a facile approach to fabricating 2D MMT membranes with alkanediamines as cross-linkers. The incorporation of diamine molecules of different lengths enables controllable interlayer spacing and strengthens interlamellar connections, leading to tunable ion transport properties and boosted membrane stability in aqueous environments.

The critical role of osteopontin (OPN) in fibrotic diseases.

Fibrosis is a pathological condition characterized by the excessive deposition of extracellular matrix components in tissues and organs, leading to progressive architectural remodelling and contributing to the development of various diseases. Osteopontin (OPN), a highly phosphorylated glycoprotein, has been increasingly recognized for its involvement in the progression of tissue fibrosis. This review provides a comprehensive overview of the genetic and protein structure of OPN and focuses on our current understanding of the role of OPN in the development of fibrosis in the lungs and other tissues. Additionally, special attention is given to the potential of OPN as a biomarker and a novel therapeutic target in the treatment of fibrosis.

Material Design Strategies for Recovery of Critical Resources from Water.

Population growth, urbanization, and decarbonization efforts are collectively straining the supply of limited resources that are necessary to produce batteries, electronics, chemicals, fertilizers, and other important products. Securing the supply chains of these critical resources via the development of separation technologies for their recovery represents a major global challenge to ensure stability and security. Surface water, groundwater, and wastewater are emerging as potential new sources to bolster these supply chains. Recently, a variety of material-based technologies have been developed and employed for separations and resource recovery in water. Judicious selection and design of these materials to tune their properties for targeting specific solutes is central to realizing the potential of water as a source for critical resources. Here, the materials that are developed for membranes, sorbents, catalysts, electrodes, and interfacial solar steam generators that demonstrate promise for applications in critical resource recovery are reviewed. In addition, a critical perspective is offered on the grand challenges and key research directions that need to be addressed to improve their practical viability.

Tunable Ion Transport with Freestanding Vermiculite Membranes.

Membranes integrating two-dimensional (2D) materials have emerged as a category with unusual ion transport and potentially useful separation applications in both aqueous and nonaqueous systems. The interlayer galleries in these membranes drive separation and selectivity, with specific transport properties determined by the chemical and structural modifications within the inherently different interlayers. Here we report an approach to tuning interlayer spacing with a single source material─exfoliated and restacked vermiculite with alkanediamine cross-linkers─to both control the gallery height and enhance the membrane stability. The as-prepared cross-linked 2D vermiculite membranes exhibit ion diffusivities tuned by the length of the selected diamine molecule. The 2D nanochannels in these stabilized vermiculite membranes enable a systematic study of confined ionic transport.

Disease Severity Determines Timing of Initiating Continuous Renal Replacement Therapies: A Systematic Review and Meta-Analysis.

Background: Timing of initiating continuous renal replacement therapies (CRRTs) among the patients with acute kidney injury (AKI) in intensive care units (ICU) has been discussed over decades, but the definition of early and late CRRT initiation is still unclear. Methods: The English language randomized controlled trials (RCTs) and cohort studies were searched through MEDLINE, EMBASE, and Cochrane Library on July 19, 2019, by the two researchers independently. The study characteristics; early and late definitions; outcomes, such as all-cause, in-hospital, 28- or 30-, 60-, 90-day mortality; and renal recovery were extracted from the 18 eligible studies. Pooled relative risk ratios (RRs) and 95% CIs were estimated with the fixed effects model and random effects model as appropriate. This study is registered with PROSPERO (CRD 42020158653). Results: Eighteen studies including 3,914 patients showed benefit in earlier CRRT (n = 1,882) over later CRRT (n = 2,032) in all-cause mortality (RR 0.78, 95% CI 0.66-0.92), in-hospital mortality (RR 0.81, 95% CI 0.67-0.99), and 28- or 30-day mortality (RR 0.81, 95% CI 0.74-0.88), but in 60- and 90-day mortalities, no significant benefit was observed. The subgroup analysis showed significant benefit in the disease-severity-based subgroups on early CRRT initiation in terms of in-hospital mortality and 28- or 30-day mortality rather than the time-based subgroups. Moreover, early CRRT was found to have beneficial effects on renal recovery after CRRT (RR 1.21, 95% CI 1.01-1.45). Conclusions: Overall, compared with late CRRT, early CRRT is beneficial for short-term survival and renal recovery, especially when the timing was defined based on the disease severity. CRRT initiation on Acute Kidney Injury Network (AKIN) stage 1 or Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE)-Risk or less may lead to a better prognosis.

Surface Zeta Potential of ALD-Grown Metal-Oxide Films.

Membranes are among the most promising technologies for energy-efficient and highly selective separations, and the surface-charge property of membranes plays a critical role in their broad applications. Atomic layer deposition (ALD) can deposit materials uniformly and with high precision and controllability on arbitrarily complex and large substrates, which renders it a promising method to tune the electrostatics of water/solid interfaces. However, a systematic study of surface-charge properties of ALD-grown films in aqueous environments is still lacking. In this work, 17 ALD-grown metal-oxide films are synthesized, and a comprehensive study of their water stability, wetting properties, and surface-charge properties is provided. This work represents a resource guide for researchers and ultimately for materials and process engineers, seeking to tailor interfacial charge properties of membranes and other porous water treatment components.

miR-26a enhances colorectal cancer cell growth by targeting RREB1 deacetylation to activate AKT-mediated glycolysis.

We previously reported the inhibitory effects of microRNA-26a (miR-26a) on the conversion of pyruvate to acetyl coenzyme A in glucose metabolism by directly targeting pyruvate dehydrogenase protein X component in colorectal cancer (CRC) cells (Chen B et al., BMC Cancer 2014). Here, using microRNA in situ hybridization, we confirmed that miR-26a levels were elevated in 77 human CRC tissue samples and further investigated the key miR-26a-mediated metabolic regulation elements and signaling pathways in CRC cells through quantitative proteomic dissection combined with cancer cell biology and biochemical loss-of-function analysis. We found that AKT transcription signaling was a target pathway via miR-26a-mediated deacetylation modification of Ras-responsive element-binding protein 1 (RREB1) at the Lys-60 residue. miR-26a improved the deacetylation level of RREB1, thus contributing to RREB1 binding to the AKT1 promoter to activate AKT transcription and its related signaling pathway in glycolysis. Moreover, miR-26a promoted CRC tumorigenesis in CRC cells and subcutaneous xenograft mice. Thus, miR-26a is a key regulator of CRC tumorigenesis that mediates the deacetylation modification of RREB1 to enhance AKT1 transcription and downstream target gene expression in glycolysis for CRC growth.

Risk of dementia in gout and hyperuricaemia: a meta-analysis of cohort studies.

OBJECTIVES: Gout, characterised by hyperuricaemia with monosodium urate crystal formation and inflammation, is the most common inflammatory arthritis in adults. Recent studies have found that elevated uric acid levels are related to the occurrence of dementia. We conducted a study to investigate the association between dementia and gout or hyperuricaemia. DESIGN: Systematic review and meta-analysis of cohort studies. DATA SOURCES: Studies were screened from inception to 28 June 2019 by searching Medline, Embase and the Cochrane Library databases. ELIGIBILITY CRITERIA: Cohort studies comparing the risk of dementia in patients with gout and hyperuricaemia versus non-gout and non-hyperuricaemia controls were enrolled. DATA EXTRACTION AND ANALYSIS: Two reviewers separately selected studies and extracted data using the Medical Subject Headings without restriction on languages or countries. The adjusted HRs were pooled using the DerSimonian and Laird random effects model. Sensitivity analyses were conducted to evaluate the stability of the results. Publication bias was evaluated using Egger's and Begg's tests. Quality assessment was performed according to the Newcastle-Ottawa Scale. RESULTS: Four cohort studies that met the inclusion criteria were included in our meta-analysis. We found that gout and hyperuricaemia did not increase the risk of dementia, with a pooled HR of 0.94 (95% CI 0.69 to 1.28), but might decrease the risk of Alzheimer's disease (AD), with a pooled HR of 0.78 (95% CI 0.64 to 0.95). There was little evidence of publication bias. Quality assessment of the included studies was high (range: 6-8 points). CONCLUSIONS: Our study shows that gout and hyperuricaemia do not increase the risk of dementia. However, gout and hyperuricaemia might have a protective effect against AD. Due to the limited number of research articles, more investigations are needed to demonstrate the potential relationship between dementia and gout or hyperuricaemia.

Comparative efficacy of different ultrasound-guided ablation for the treatment of benign thyroid nodules: Systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Percutaneous ablation is currently deemed an additionally treatment option for benign thyroid nodules in the world, but possibly different effect among the ablation modalities is not clear. So we aim to evaluate the efficacy and complications of thermal/chemical ablation by network meta-analysis. MATERIALS AND METHODS: In the network meta-analysis, PubMed, EMBASE and the Cochrane Library databases were searched from 1980 to 2020. Studies of adults with thyroid benign nodules under percutaneous ablation therapy were included. Percentage mean volume change, symptom score change, cosmetic score change and complications were evaluated by network meta-analysis. RESULTS: In the network meta-analysis, Radiofrequency Ablation(RFA) with 2 treatment sessions group was associated with the highest reduction for the mean volume change during 6-month follow-up (MD = 79.09 and 95% CrI:48.23-89.94). There is no significant difference in the incidence of complications. Subgroup analysis showed that 2 sessions of Radiofrequency Ablation (RFA) ranks the highest probability (surface under the cumulative ranking curve (SUCRA) values 77.9) of being the most efficacious treatment for solid or predominantly solid benign nodules. Ethanol ablation (EA) ranked first (SUCRA value 81.1) in the treatment for cyst or predominantly cyst benign nodules. CONCLUSION: RFA appears to be superior to other US-guided percutaneous ablation in reducing benign thyroid nodule volume during short- and long-term follow-up. In the subgroup analysis, RFA with 2 treatment sessions showed the most significant effectiveness for solid benign thyroid nodules and EA showed more effectiveness to decrease the volume of cyst benign thyroid nodules.

Case Report: Multicentric Reticulohistiocytosis Associated With Posterior Mediastinal Adenosquamous Carcinoma, Antinuclear Antibody Positivity and Lupus Anticoagulant Positivity.

Multicentric reticulohistiocytosis (MRH) is a rare systemic disease of non-Langerhans cell histiocytosis. A number of studies in the literature have documented that it can coexist with malignancy or autoimmune disease, making it difficult to determine the most appropriate therapy. Here, we present a case study of MRH associated with posterior mediastinal adenosquamous carcinoma along with antinuclear antibody positivity and lupus anticoagulant positivity. The patient experienced 6 months of clinical benefit after surgical resection and chemoradiotherapy of the mediastinal malignancy. This case adds to the available literature on multicentric reticulohistiocytosis associated with different types of malignancy and provides supplementary clinical data on the coexistence of this syndrome with malignancy and immune system abnormalities. To the best of our knowledge, this is the first case study describing MRH accompanied by posterior mediastinal adenosquamous carcinoma and lupus anticoagulant positivity. The unknown aetiology and polymorphic clinical presentation of MRH warrants further investigation.

Pterostilbene, a Bioactive Component of Blueberries, Alleviates Renal Interstitial Fibrosis by Inhibiting Macrophage-Myofibroblast Transition.

Pterostilbene (PTB) is a derivative of resveratrol present in grapes and blueberries. PTB is structurally similar to resveratrol, possessing properties such as being analgesic, anti-aging, antidiabetic, anti-inflammatory, anti-obesity, anti-oxidation, cholesterol-reductive, and neuroprotective. However, there have not been reports on the effect of PTB on macrophage-myofibroblast transition (MMT) induced fibrosis in kidney. In this study, we investigated the antifibrotic effects of PTB on the in vivo mouse unilateral ureteral obstruction (UUO) model and in vitro MMT cells. Kidneys subjected to UUO with PTB treatment were collected for the investigation of PTB mediating MMT derived renal interstitial fibrosis. We conducted kidney RNA-seq transcriptomes and TGF-[Formula: see text]1-induced bone marrow-derived macrophages assays to determine the mechanisms of PTB. We found that PTB treatment suppressed the interstitial fibrosis in UUO mice. PTB also attenuated the number of MMT cells in vivo and in vitro. The transcriptomic analysis showed that CXCL10 may play a central role in the process of PTB-treated renal fibrosis. The siRNA-mediated CXCL10 knockdown decreased the number of MMT cells in TGF-[Formula: see text]1-induced bone marrow-derived macrophages. Our results suggested that PTB attenuated renal interstitial fibrosis by mediating MMT by regulating transcriptional activity of CXCL10.

Inhibition of Fatty Acid-Binding Protein 4 Attenuated Kidney Fibrosis by Mediating Macrophage-to-Myofibroblast Transition.

The macrophage-to-myofibroblast transition (MMT) process is an important pathway that contributing to renal interstitial fibrosis (RIF). Fatty acid-binding protein 4 (FABP4) deteriorated RIF via promoting inflammation in obstructive nephropathy. However, the clinical significance of FABP4 in fibrotic kidney disease remains to be determined and little is known of the FABP4 signaling in MMT. Biopsy specimens of chronic kidney disease patients and kidneys subjected to unilateral ureteral obstruction (UUO) of FABP4-deficient mice or FABP4 inhibitor-treated mice were collected for the investigation of FABP4 mediating MMT of RIF. We conducted kidney RNA-seq transcriptomes and TGF-ß1-induced bone marrow-derived macrophage (BMDM) assays to determine the mechanisms of FABP4. We found that FABP4 expression correlated with RIF in biopsy specimens and the injured kidneys of UUO mice where FABP4 was co-expressed with MMT cells. In UUO mice, FABP4 deficiency and a highly selective FABP4 inhibitor BMS309403 treatment both suppressed RIF. FABP4 ablation also attenuated the UUO-induced number of MMT cells and serum amyloid A1 (Saa1) expression. The siRNA-mediated Saa1 knockdown decreased the number of MMT cells in vitro. In conclusion, FABP4 is an important factor contributing to RIF by mediating MMT, and genetic/pharmacological inhibition of FABP4 provides a novel approach for the treatment of kidney fibrosis.

The comparison of different antiviral therapies on the prognosis of hepatitis B virus-related hepatocellular carcinoma after curative treatments: A network meta-analysis.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of different nucleos(t)ide analogues in the prognosis of HBV-related hepatocellular carcinoma (HCC) patients after curative treatment by network meta-analysis. METHODS: Literature retrieval was conducted in globally recognized databases, namely, PubMed, EMBASE, Cochrane Library databases, and Science Citation Index Expanded, to address relative studies investigating nucleot(s)ide analogues for HBV-related HCC patients after curative resection. Relative parametric data, including 1-, 3-, and 5-year overall survival rate and 1-, 3-, and 5-year recurrence-free survival rate were quantitatively pooled and estimated. The inconsistency factor, the cumulative ranking curve, and the publication bias were evaluated. RESULTS: Fourteen observational studies of 2481 adults performed between 2000 and 2019 were eligible. In terms of overall survival, ADV (Adefovir dipivoxil) (Odds ratio (OR): 2.35, 95% confidence interval (CI): 1.17-4.73), Lamivudine (OR: 2.08, 95% CI: 1.78-5.58), and Entecavir (OR: 2.14, 95% CI: 1.59-2.88) were found to be more beneficial than control group while ADV has the highest probability of having the most efficacious treatment (SCURA values 66.3) for 5-year overall survival. In late recurrence-free survival, ADV (OR = 1.88, 95% CI: 1.77-4.60), Entecavir (OR = 1.96, 95% CI: 1.36-2.55), and Lamivudine (OR = 1.73, 95% CI: 1.06-2.82) all had better significant prognosis than patients without antiviral therapy postoperatively and patients with ADV as postoperative antiviral therapy has significantly recurrence-free survival benefit at 5-year follow-up compared to those undertaking Entecavir (OR = 1.96, 95% CI: 1.52-7.38) and Lamivudine (OR = 1.39, 95% CI: 1.09-3.01). Moreover, the application of ADV possessed the highest possibility of having the best clinical effects on 1- (surface under the cumulative ranking probabilities (SUCRA), 64.7), 3- (SUCRA, 64.7), and 5-year (SUCRA, 70.4) recurrence survival rate for HBV-related HCC patients. CONCLUSIONS: Patients with postoperative nucleos(t)ide analogues antiviral therapy had better survival benefit than those without antiviral therapy for HBV-related HCC patients after curative treatment. Additionally, nucleotide analogues like ADV and Tenofovir disoproxil fumarate has better impact on early and late recurrence-free survival of patients after curative treatment than those undertaking nucleoside analogues.

Transcription Factor RREB1: from Target Genes towards Biological Functions.

The Ras-responsive element binding protein 1(RREB1) is a member of zinc finger transcription factors, which is widely involved in biological processes including cell proliferation, transcriptional regulation and DNA damage repair. New findings reveal RREB1 functions as both transcriptional repressors and transcriptional activators for transcriptional regulation of target genes. The activation of RREB1 is regulated by MAPK pathway. We have summarized the target genes of RREB1 and discussed RREB1 roles in the cancer development. In addition, increasing evidences suggest that RREB1 is a potential risk gene for type 2 diabetes and obesity. We also review the current clinical application of RREB1 as a biomarker for melanoma detection. In conclusion, RREB1 is a promising diagnostic biomarker or new drug target for cancers and metabolic diseases.

Activation of GPR120 by TUG891 ameliorated cisplatin-induced acute kidney injury via repressing ER stress and apoptosis.

Activation of G protein-coupled receptor 120 (GPR120) could inhibit apoptosis and inflammation in cerebral ischemic injury and liver ischemia-reperfusion injury. However, whether GPR120 agonism exerted potential for cisplatin-induced acute kidney injury and the involved mechanisms remained unknown. In our study, pharmacological activation of GPR120 by TUG891 treatment remarkably reduced the elevated serum creatinine level and attenuated tubular injury. Cisplatin triggered ATF6, PERK and IRE1 pathways of unfolded protein response (UPR) of ER stress in the injured kidney tissue, as well as the downstream molecules eIF2α, ATF4 and XBP1. Protein of ER stress-mediated apoptosis, CHOP, was overexpressed in the cisplatin group. Oral application of TUG891 displayed effective inhibition of ER stress and apoptosis. TUG891 treatment significantly decreased the TUNEL positive cells and the flow cytometry of HK-2 cells delineated the similar results that the apoptosis rates were considerably reduced in the TUG891 group compared to cisplatin group. Collectively, activation of GPR120 by TUG891 exhibited renal protection against cisplatin-induced AKI via suppressing ER-associated apoptosis in tubular epithelial cells.

2-Methylquinazoline derivative 23BB as a highly selective histone deacetylase 6 inhibitor alleviated cisplatin-induced acute kidney injury.

Histone deacetylases 6 (HDAC6) has been reported to be involved in the pathogenesis of cisplatin-induced acute kidney injury (AKI). Selective inhibition of HDAC6 might be a potential treatment for AKI. In our previous study, a highly selective HDAC6 inhibitor (HDAC6i) 23BB effectively protected against rhabdomyolysis-induced AKI with good safety. However, whether 23BB possessed favorable renoprotection against cisplatin-induced AKI and the involved mechanisms remained unknown. In the study, cisplatin-injected mice developed severe AKI symptom as indicated by acute kidney dysfunction and pathological changes, companied by the overexpression of HDAC6 in tubular epithelial cells. Pharmacological inhibition of HDAC6 by the treatment of 23BB significantly attenuated sCr, BUN and renal tubular damage. Mechanistically, 23BB enhanced the acetylation of histone H3 to reduce the HDAC6 activity. Cisplatin-induced AKI triggered multiple signal mediators of endoplasmic reticulum (ER) stress including PERK, ATF6 and IRE1 pathway, as well as CHOP, GRP78, p-JNK and caspase 12 proteins. Oral administration of our HDAC6i 23BB at a dose of 40 mg/kg/d for 3 days notably improved above-mentioned responses in the injured kidney tissues. HDAC6 inhibition also reduced the number of TUNEL-positive tubular cells and regulated apoptosis-related protein expression. Overall, these data highlighted that HDAC6 inhibitor 23BB modulated apoptosis via the inhibition of ER stress in the tubular epithelial cells of cisplatin-induced AKI.

Multifunctional Pharmaceutical Effects of the Antibiotic Daptomycin.

Daptomycin (DAP), a cyclic lipopeptide produced by Streptomyces roseosporus, is a novel antibiotic to clinically treat various Gram-positive pathogenic bacteria-induced infections. Although DAP has a strong broad-spectrum bactericidal effect, recently rare bacterial antibiotic resistance against DAP gradually arises. The review is to summarize the normal indications of DAP, its off-label usage against several clinical pathogen infections, the unique antibacterial mechanisms of DAP, and the combination of antibiotic therapies for highly DAP-resistant pathogens. More noticeably, rising evidences demonstrate that DAP has new potential activity of anticancer and immunomodulatory effects. So far the multifunctional pharmaceutical effects of DAP deserve to be further explored for future clinical applications.