The changes of blood-based inflammatory biomarkers after non-pharmacologic interventions for chronic low back pain: a systematic review.

BACKGROUND: Chronic low back pain (CLBP) is a prevalent and debilitating condition, leading to significant challenges to both patients and the governmental healthcare system. Non-pharmacologic interventions have received increasing attention as potential strategies to alleviate chronic low back pain and improve patient outcomes. The aim of this systematic review was to comprehensively assess the changes in blood inflammatory biomarkers after non-pharmacologic interventions for CLBP patients, thus trying to understand the complex interactions between non-pharmacologic interventions and inflammatory biomarker changes in CLBP. METHODS: A thorough search (from January 1st, 2002 to October 5th, 2022) of PubMed, Medline (platform Web of Science), and the Cochrane Library (platform Wiley Online Library) were conducted, and inclusion criteria as well as exclusion criteria were refined to selection of the studies. Rigorous assessments of study quality were performed using RoB 2 from Cochrane or an adaptation of the Downs and Black checklist. Data synthesis includes alterations in inflammatory biomarkers after various non-pharmacologic interventions, including exercise, acupressure, neuro-emotional technique, and other modalities. RESULTS: Thirteen primary studies were included in this systematic review, eight randomized controlled trials, one quasi-randomized trial, and four before-after studies. The interventions studied consisted of osteopathic manual treatment (one study), spinal manipulative therapy (SMT) (three studies), exercise (two studies), yoga (two studies) and acupressure (two studies), neuro-emotional technique (one study), mindfulness-based (one study) and balneotherapy study (one study). Four studies reported some changes in the inflammatory biomarkers compared to the control group. Decreased tumor necrosis factor-alpha (TNF-α) after osteopathic manual treatment (OMT), neuro-emotional technique (NET), and yoga. Decreased interleukin (IL)-1, IL-6, IL-10, and c-reactive protein (CRP) after NET, and increased IL-4 after acupressure. Another five studies found changes in inflammatory biomarkers through pre- and post-intervention comparisons, indicating improvement outcomes after intervention. Increased IL-10 after balneotherapy; decreased TNF-α, IL-1ß, IL-8, Interferon-gamma, interferon-γ-induced protein 10-γ-induced protein 10 after exercise; decreased IL-6 after exercise and SMT; decreased CRP and chemokine ligand 3 after SMT. CONCLUSION: Results suggest a moderation of inflammatory biomarkers due to different non-pharmacologic interventions for CLBP, generally resulting in decreased pro-inflammatory markers such as TNF-α and IL-6 as well as increased anti-inflammatory markers such as IL-4, thus revealing the inhibition of inflammatory processes by different non-pharmacologic interventions. However, a limited number of high-quality studies evaluating similar interventions and similar biomarkers limits the conclusion of this review.

Crystalline silica-induced endoplasmic reticulum stress promotes the pathogenesis of silicosis by augmenting proinflammatory interstitial pulmonary macrophages.

Crystalline silica (CS) particles are ubiquitously present in the environment, particularly in occupational settings, and exposure to respirable CS causes silicosis, imposing a significant disease burden. However, the pathogenesis of silicosis remains unclear. Exposure to external stimuli, such as CS, leads to the accumulation of unfolded proteins and triggers endoplasmic reticulum (ER) stress, disrupting tissue immune homeostasis and accelerating pathological progression. While pulmonary macrophages phagocytose CS particles to initiate the immune response, the role of ER stress in this process is unknown. Herein, we used a murine model of silicosis to simulate the pathological progression from acute inflammation to fibrosis in silicosis and conducted in vivo pharmacological inhibition of ER stress to explore the underlying mechanism. Using flow cytometry, we further classified pulmonary macrophages into monocyte-like macrophages (monocytes), interstitial macrophages (IMs), and alveolar macrophages (AMs). Our results showed that CS-induced ER stress primarily contributed to the augmentation of IMs and thereby exerted a significant impact on pulmonary macrophages. Despite coexpressing M1- and M2-like markers, IMs predominantly exhibited an M1-like polarization state and played a proinflammatory role by expressing the cytokines pro-IL-1ß and TNF-α during the pathological progression of silicosis. Additionally, IMs recruited by CS-induced ER stress also exhibited high expression of MHCII and exerted active immunomodulatory effects. Overall, our study demonstrates that ER stress induced by CS particles triggers a proinflammatory immune microenvironment dominated by IMs and reveals novel insights into the pulmonary toxicological effects of CS particles.

Association of TyG index and central obesity with hypertension in middle-aged and elderly Chinese adults: a prospective cohort study.

Triglyceride glucose index (TyG) and waist circumstance have been well documented to be highly correlated with hypertension. However, the joint effect of waist circumstance and TyG on the risk of hypertension is unknown in middle-aged and elderly Chinese adults. The purpose of this study was to investigate the association between TyG and the risk of new-onset hypertension in middle-aged and elderly Chinese individuals with different waist circumstances. The multicentred prospective cohort study was conducted in 28 provinces of China including a total of 5865 eligible participants aged ≥ 45 years old. Cox regression was performed to examine the relationship of TyG index and hypertension with adjustments for the pertinent variables. Besides, the relationship was explored in different groups on the basis of waist circumstance. There was no significant correlation between TyG index and new-onset hypertension after adjustment for pertinent variables (hazards ratio [HR]: 0.99; 95% confidence interval [CI]: 0.80-1.24). When the association was explored in different waist circumstance groups, multivariate cox regression analyses revealed that TyG was an independent factor positively associated with the risk of hypertension in central obesity prophase group (HR: 1.57; 95% CI 1.13-2.16). Among individuals with central obesity, relative to population with lower TyG (Q1: 4.96-8.18), people who had higher TyG (Q3: 8.52-8.95; Q4: 8.95-12.14) were associated with significantly lower HR for hypertension. There was no conspicuous correlation between TyG index with new-onset hypertension in normal waist circumstance (HR: 1.05; 95% CI 0.84-1.30). The research demonstrated the positive relationship of TyG with risk of hypertension among individuals with central obesity prophase, negative relationship of TyG with hypertension among population with central obesity and inconspicuous correlation of TyG with hypertension among individuals with normal waist. In conclusion, the study findings supported the combined effects of TyG index and waist circumference in predicting hypertension in middle-aged and elderly Chinese individuals.

Crystalline silica-induced recruitment and immuno-imbalance of CD4+ tissue resident memory T cells promote silicosis progression.

Occupational crystalline silica (CS) particle exposure leads to silicosis. The burden of CS-associated disease remains high, and treatment options are limited due to vague mechanisms. Here we show that pulmonary CD4+ tissue-resident memory T cells (TRM) accumulate in response to CS particles, mediating the pathogenesis of silicosis. The TRM cells are derived from peripheral lymphocyte recruitment and in situ expansion. Specifically, CD69+CD103+ TRM-Tregs depend more on circulating T cell replenishment. CD69 and CD103 can divide the TRM cells into functionally distinct subsets, mirroring the immuno-balance within CD4+ TRM cells. However, targeting CD103+ TRM-Tregs do not mitigate disease phenotype since the TRM subsets exert immunosuppressive but not pro-fibrotic roles. After identifying pathogenic CD69+CD103- subsets, we highlight IL-7 for their maintenance and function, that present a promising avenue for mitigating silicosis. Together, our findings highlight the distinct role of CD4+ TRM cells in mediating CS-induced fibrosis and provide potential therapeutic strategies.

Corrigendum: Identification of ACKR4 as an immune checkpoint in pulmonary arterial hypertension.

[This corrects the article DOI: 10.3389/fimmu.2023.1153573.].

A new andrographolide derivative ADA targeting SIRT3-FOXO3a signaling mitigates cognitive impairment by activating mitophagy and inhibiting neuroinflammation in Apoe4 mice.

BACKGROUND: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and mitophagy deficit was identified as the typical abnormality in early stage of AD. The neuroprotective effect of andrographolide (AGA) has been confirmed, anda acetylated derivative of AGA (3,14,19-triacetylandrographolide, ADA) was considered to have stronger efficacy. PURPOSE: The current study aims to investigate the impact of ADA on cognitive ability in a sporadic AD model and explore its potential mechanism. STUDY DESIGN/ METHODS: Apoe4 mouse was adopted for evaluating the impact of AGA on cognitive impairment through a serious of behavioral tests. The molecular mechanism of ADA involved in mitophagy and neuroinflammation was investigated in detailby Western blot, ELISA, immunofluorescence and transmission electron microscopy in Apoe4 mice, as well as Apoe4-transfected BV2 cells and HT22 cells. RESULTS: ADA application significantly improved cognitive impairment of Apoe4 mice, and lessened Aß load and neuronal damage, which has stronger activity than its prototype AGA. Accumulated mitophagy markers LC3II, P62, TOM20, PINK1 and Parkin, and decreased mitophagy receptor BNIP3 in hippocampus of Apoe4 mice were greatly reversed after ADA treatment. Meanwhile, ADA promoted the recruitment of BNIP3 to mitochondria, and the transport of damaged mitochondria to lysosome, indicating that disturbed mitophagy in AD mice was restored by ADA. Inhibited SIRT3 and FOXO3a in Apoe4 mice brains were elevated after ADA treatment. ADA also lightened the neuroinflammation caused by NLRP3 inflammasome activation. Additionally, damaged mitophagy and/or activated NLRP3 inflammasome were also observed in BV2 cells and HT22 cells transfected with Apoe4, all of which were rescued by ADA incubation. Noteworthily, SIRT3 inhibitor 3-TYP could abolish the impact of ADA on mitophagy and NLRP3 inflammasome in vitro. CONCLUSION: ADA exerted stronger cognition-enhancing ability in relative to AGA, and ADA could repaire mitophagy deficiency via SIRT3-FOXO3a pathway, and subsequently inhibite NLRP3 inflammasome to mitigate AD pathology.

RNA m6A methylation and regulatory proteins in pulmonary arterial hypertension.

m6A (N6­methyladenosine) is the most common and abundant apparent modification in mRNA of eukaryotes. The modification of m6A is regulated dynamically and reversibly by methyltransferase (writer), demethylase (eraser), and binding protein (reader). It plays a significant role in various processes of mRNA metabolism, including regulation of transcription, maturation, translation, degradation, and stability. Pulmonary arterial hypertension (PAH) is a malignant cardiopulmonary vascular disease characterized by abnormal proliferation of pulmonary artery smooth muscle cells. Despite the existence of several effective and targeted therapies, there is currently no cure for PAH and the prognosis remains poor. Recent studies have highlighted the crucial role of m6A modification in cardiovascular diseases. Investigating the role of RNA m6A methylation in PAH could provide valuable insights for drug development. This review aims to explore the mechanism and function of m6A in the pathogenesis of PAH and discuss the potential targeting of RNA m6A methylation modification as a treatment for PAH.

Pickering Emulsions Stabilized by Conjugated Zein-Soybean Polysaccharides Nanoparticles: Fabrication, Characterization and Functional Performance.

This study aims to fabricate zein-based colloidal nanoparticles, which were used to stabilize Pickering emulsions, by conjugation with soybean polysaccharide (SSPS) through the Maillard reaction. The physicochemical properties of the conjugated particles as well as the physical and oxidative stability of the fabricated Pickering emulsion that utilized conjugated colloidal particles with the volumetric ratio of water and oil at 50:50 were investigated. The grafting degree of zein and SSPS was verified through examination of FT-IR and fluorescence. Moreover, the conjugated Zein/SSPS nanoparticles (ZSP) that were prepared after dry heating for 48-72 h exhibit excellent colloidal stability across a range of pH values (4.0-10.0). Further, the wettability of ZSP decreased based on a contact angle analysis of θ~87°. Confocal laser scanning microscopy (CLSM) images indicated that ZSP particles were located around the oil droplets. Additionally, the ZSP effectively improved the oxidative stability of the Pickering emulsions, as demonstrated by a significant decrease in both peroxide value (PV) and thiobarbituric acid reactive substances (TBARS). The results of this study demonstrate that ZSP represents a promising food-grade Pickering emulsifier, capable of not only stabilizing emulsions but also inhibiting their oil oxidation.