An innovative dual-organelle targeting NIR fluorescence probe for detecting hydroxyl radicals in biosystem and inflammation models.

The hydroxyl radical (OH) is highly reactive and plays a significant role in a number of physiological and pathological processes within biosystems. Aberrant changes in the level of hydroxyl radical are associated with many disorders including tumor, inflammatory and cardiovascular diseases. Thus, detecting reactive oxygen species (ROS) in biological systems and imaging them is highly significant. In this work, a novel fluorescent probe (HR-DL) has been developed, targeting two organelles simultaneously. The probe is based on a coumarin-quinoline structure and exhibits high selectivity and sensitivity towards hydroxyl radicals (OH). When reacting with OH, the hydrogen abstraction process released its long-range π-conjugation and ICT processes, leading to a substantial red-shift in wavelength. This probe has the benefits of good water solubility (in its oxidative state), short response time (within 10 s), and unique dual lysosome/mitochondria targeting capabilities. It has been applied for sensing OH in biosystem and inflammation mice models.

Exposure to four typical heavy metals induced telomere shortening of peripheral blood mononuclear cells in relevant with declined urinary aMT6s in rats.

Environmental heavy metals pollution have seriously threatened the health of human beings. An increasing number of researches have demonstrated that environmental heavy metals can influence the telomere length of Peripheral Blood Mononuclear Cells (PBMCs), which implicate biological aging as well as predicts diseases. Our previous study has shown that methylmercury (MeHg)-induced telomere shortening in rat brain tissue was associated with urinary melatonin metabolite 6-sulfatoxymelatonin (aMT6s) levels. Here, we aimed to further elucidate the impact of 4 typical heavy metals (As, Hg, Cd and Pb) on telomere length of PBMCs and their association with urinary aMT6s in rats. In this study, eighty-eight male Sprague-Dawley rats were randomized grouped into eleven groups. Among them, forty 3-month-old (young) and forty 12-month-old (middle-aged) rats were divided into young or middle-aged control groups as well as typical heavy metals exposed groups, respectively. Eight 24-month-old rats (old) was divided into aging control group. The results showed that MeHg exposure in young rats while sodium arsenite (iAs), MeHg, cadmium chloride (CdCl2), lead acetate (PbAc) exposure in middle-aged rats for 3 months significantly reduced the levels of and urinary aMT6s, as well as telomere length of PBMCs. In addition, they also induced abnormalities in serum oxidative stress (SOD, MDA and GPx) and inflammatory (IL-1ß, IL-6 and TNF-α) indicators. Notably, there was a significant positive correlation between declined level of urinary aMT6s and the shortening of telomere length in PBMCs in rats exposed to 4 typical heavy metals. These results suggested that 4 typical heavy metals exposure could accelerate the reduction of telomere length of PBMCs partially by inducing oxidative stress and inflammatory in rats, while ageing may be an important synergistic factor. Urinary aMT6s detection may be a alternative method to reflect telomere toxic effects induced by heavy metal exposure.

TAK1 expression is associated with increased PD-L1 and decreased cancer-specific survival in microsatellite-stable colorectal cancer.

BACKGROUND: Transforming growth factor ß-activated protein kinase-1 (TAK1) plays an important role in MAPK and NFκB pathways and has been associated with colorectal cancer. The aim of this study was to determine how cytoplasmic and juxtanuclear punctate staining of TAK1 relates to immune checkpoint expression and cancer specific survival in colorectal cancer. METHODS: Protein expression was assessed by immunohistochemistry on tissue microarrays from primary curative colorectal cancer resected specimens. Expression levels of cytoplasmic TAK1 by QuPath digital quantification and punctate TAK1 staining was scored using a manual point scoring technique and correlated with clinicopathological features, immune checkpoint expression and cancer-specific survival. Bulk RNA sequencing was performed in specimens to determine mutational profiles and differentially expressed genes. RESULTS: A cohort of 875 patients who had undergone colorectal cancer resection were assessed for TAK1 expression. Higher levels of cytoplasmic TAK1 expression correlated with elevated PD1 and PD-L1 expression (p < 0.010). High punctate TAK1 expression was more commonly identified in poorly differentiated colorectal cancers (p = 0.036), had dysregulated mutational and transcriptional profiles with decreased insulin-like growth factor 2(IGF2) expression (p < 0.010), and independently predicted poor cancer-specific survival (HR 2.690, 95% CI 1.419-5.100, p = 0.002). The association of punctate TAK1 expression and recurrence remained after subgroup analysis for microsatellite-stable colorectal cancer (p = 0.028). DISCUSSION: Punctate TAK1 expression is associated with worse cancer specific survival. TAK1 signalling may be an important pathway to investigate underlying mechanisms for recurrence in microsatellite-stable colorectal cancer.

Jian-Pi-Yi-Shen formula ameliorates renal fibrosis-induced anemia in rats with chronic kidney disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Jian-Pi-Yi-Shen (JPYS) formula is an effective herbal therapy against renal injury, and JPYS has been clinically applied to ameliorate chronic kidney disease (CKD) and CKD-associated anemia. Increasing evidence supports the link between renal fibrosis and anemia in CKD. JPYS possessed anti-fibrosis effects in experimental CKD. Nevertheless, research on the mechanisms of JPYS in ameliorating renal anemia (RA) through suppressing renal fibrosis remains to be clarified. AIM OF THE STUDY: Our study here was carried out to investigate the mechanisms of JPYS in protecting against RA. MATERIALS AND METHODS: An adenine-induced anemia model in rats with CKD at three different time points was established, and bio-samples taken from each group were analyzed. Biochemical analysis was employed to detect kidney function and hematological parameters. Masson staining was used to evaluate renal fibrosis of rats. Western blot and immunohistochemistry were utilized to evaluate the expressions of fibrotic markers, erythropoietin (EPO) and hypoxia inducible factor-2α (HIF-2α) in the kidneys of rats. Subsequently, transcriptomic analysis was conducted to disclose the possible mechanisms of JPYS in treating RA. Finally, the expression levels of key targets were analyzed and validated by using western blot and enzyme-linked immunosorbent assay (ELISA). RESULTS: JPYS treatment improved kidney function, suppressed renal fibrosis and enhanced hematological parameters in CKD rats. Moreover, JPYS treatment restored the increased expression levels of fibrotic markers and the declined EPO with time dependence. In parallel, data indicated JPYS treatment stimulated the translocation of HIF-2α into nucleus in the renal interstitium and thus promoted the expression of EPO. Transcriptomic profiling disclosed that activations of both nuclear factor kappa B (NF-κB) and transforming growth factor-ß (TGF-ß)/Smad pathways were closely associated with RA. Ultimately, experimental validation results presented that the increased expressions of target proteins from the above-mentioned two pathways in the kidneys were decreased significantly after JPYS treatment. CONCLUSION: Our findings suggest that JPYS may improve RA by alleviating renal fibrosis, and the mechanisms of which involve in inhibiting the NF-κB and TGF-ß/Smad pathways.

Toxicological evaluation of primary particulate matter emitted from combustion of aviation fuel.

Recently, Sustainable Aviation Fuel (SAF) blends and novel combustion technologies have been introduced to reduce aircraft engine emissions. However, there is limited knowledge about the impact of combustion technology and fuel composition on toxicity of primary Particulate Matter (PM) emissions, comparable to regulated non-volatile PM (nvPM). In this study, primary PM was collected on filters using a standardised approach, from both a Rich-Quench-Lean (RQL) combustion rig and a bespoke liquid fuelled Combustion Aerosol Standard (CAST) Generator burning 12 aviation fuels including conventional Jet-A, SAFs, and blends thereof. The fuels varied in aromatics (0-25.2%), sulphur (0-3000 ppm) and hydrogen (13.43-15.31%) contents. Toxicity of the collected primary PM was studied in vitro utilising Air-Liquid Interface (ALI) exposure of lung epithelial cells (Calu-3) in monoculture and co-culture with macrophages (differentiated THP-1 cells). Cells were exposed to PM extracted from filters and nebulised from suspensions using a cloud-based ALI exposure system. Toxicity readout parameters were analysed 24h after exposure. RESULTS: showed presence of genotoxicity and changes in gene expression at dose levels which did not induce cytotoxicity. DNA damage was detected through Comet assay in cells exposed to CAST generated samples. Real-Time PCR performed to investigate the expression profile of genes involved in oxidative stress and DNA repair pathways showed different behaviours after exposure to the various PM samples. No differences were found in pro-inflammatory interleukin-8 secretion. This study indicates that primary PM toxicity is driven by wider factors than fuel composition, highlighting that further work is needed to substantiate the full toxicity of aircraft exhaust PM inclusive of secondary PM emanating from numerous engine technologies across the power range burning conventional Jet-A and SAF.

The ester-containing prodrug NT-0796 enhances delivery of the NLRP3 inflammasome inhibitor NDT-19795 to monocytic cells expressing carboxylesterase-1.

NT-0796 is an ester prodrug which is metabolized by carboxylesterase-1 (CES1) to yield the carboxylic acid NDT-19795, an inhibitor of the NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome. When applied to human monocytes/macrophages which express CES1, however, NT-0796 is much more potent at inhibiting NLRP3 inflammasome activation than is NDT-19795. Comparison of the binding of NDT-19795 and NT-0796 in a cell-based NLRP3 target engagement assay confirms that NDT-19795 is the active species. Moreover, microsomes expressing CES1 efficiently convert NT-0796 to NDT-19795, confirming CES1-dependent activation. To understand the basis for the enhanced potency of the ester prodrug species in human monocytes, we analyzed the accumulation and de-esterification of NT-0796 in cultured cells. Our studies reveal NT-0796 rapidly accumulates in cells, achieving estimated cellular concentrations above those applied to the medium, with concomitant metabolism to NDT-19795 in CES1-expressing cells. Using cells lacking CES1 or a poorly hydrolysable NT-0796 analog demonstrated that de-esterification is not required for NT-0796 to achieve high cellular levels. As a result of a dynamic equilibrium whereby NDT-19795 formed intracellularly is subsequently released to the medium, concentrations of NT-0796 sufficient to inhibit NLRP3 can be completely metabolized to NDT-19795 resulting in a transient pharmacodynamic response. In contrast, when NDT-19795 is applied directly to cells observed cell-associated levels are below those present in the medium and remain stable over time. Dynamics observed within the context of a closed tissue culture system highlight the utility of NT-0796 as a vehicle for delivering the NDT-19795 acid payload to CES1 expressing cells.

Alcohol hangover versus dehydration revisited: The effect of drinking water to prevent or alleviate the alcohol hangover.

The alcohol hangover is a combination of negative mental and physical symptoms which can be experienced after a single episode of alcohol consumption, starting when blood alcohol concentration (BAC) approaches zero. A popular theory suggests that dehydration is the primary cause of alcohol hangover and that the consumption of water could alleviate hangover symptoms. Here, the current evidence on the relationship between hangover severity, thirst, and water consumption is summarized. The positive correlations of the amount of water consumed with both hangover severity and thirst suggest that both dehydration and the hangover are co-occurring after-effects of alcohol consumption. While hangovers were typically relatively enduring, dehydration effects were usually mild and short-lasting. Survey data revealed that water consumption during or directly after alcohol consumption had only a modest effect in preventing next-day hangover. Also, the amount of water consumed during hangover was not related to changes of hangover severity and thirst. Thus, water consumption was not effective to alleviate the alcohol hangover. Taken together, these data suggests that alcohol hangover and dehydration are two co-occurring but independent consequences of alcohol consumption.

Novel tracers to assess myocardial inflammation with radionuclide imaging.

Myocardial inflammation plays a central role in the pathophysiology of various cardiac diseases. While FDG-PET is currently the primary method for molecular imaging of myocardial inflammation, its effectiveness is hindered by physiological myocardial uptake as well as its propensity for uptake by multiple disease-specific mechanisms. Novel radiotracers targeting diverse inflammatory immune cells and molecular pathways may provide unique insight through the visualisation of underlying mechanisms central to the pathogenesis of inflammatory cardiac diseases, offering opportunities for increased understanding of immunocardiology. Moreover, the potentially enhanced specificity may lead to better quantification of disease activity, aiding in the guidance and monitoring of immunomodulatory therapy. This review aims to provide an update on advancements in non-FDG radiotracers for imaging myocardial inflammatory diseases, with a focus on cardiac sarcoidosis, myocarditis, and acute myocardial infarction.

Evaluation of ß2-microglobulin in the condition and prognosis of psoriasis patients.

BACKGROUND: Numerous studies have linked the inflammatory pathway in psoriasis and metabolic disease, while no specific marker defined it. It is worth exploring the association of ß2-microglobulin (ß2M) in psoriasis severity and comorbidities. OBJECTIVES: To investigate the correlation between blood ß2M level and psoriasis severity, to explore the inflammatory factors influencing the occurrence of psoriasis comorbidities such as arthritis, diabetes, and hypertension. METHODS: Ninety-seven psoriasis patients were analyzed in the cohort retrospective study during 12 weeks. RESULTS: Significantly higher levels of blood ß2M and ESR were observed in the group that patients' PASI ≥10 than in the group that PASI <10. Blood ß2M level had strong significantly positive correlations with the PASI in Pearson's correlation analysis. In the model that systemic inflammatory factors to find psoriasis comorbidity risk factors, logistic regression analysis showed that blood ß2M level was the significant risk factor associated with diabetes and hypertension. High-sensitivity C-reactive protein (hsCRP) was the significant risk factor associated with arthritis. CONCLUSIONS: Patients with a severer psoriasis tended to have higher blood ß2M levels and severer inflammatory state. In the systemic inflammation indexes, the level of blood ß2M affected the risk of hypertension and diabetes, and hsCRP affected the risk of arthritis in patients with psoriasis.

Association of systemic immune inflammatory index with obesity and abdominal obesity: A cross-sectional study from NHANES.

BACKGROUND AND AIM: Our aim was to explore the potential relationship between SII and obesity, as well as abdominal obesity. METHODS AND RESULTS: We utilized a weighted multivariable logistic regression model to investigate the relationship between SII and obesity, as well as abdominal obesity. Generalized additive models were employed to test for non-linear associations. Subsequently, we constructed a two-piecewise linear regression model and conducted a recursive algorithm to calculate inflection points. Additionally, subgroup analyses and interaction tests were performed. A total of 7,880 U.S. adult participants from NHANES 2011-2018 were recruited for this study. In the regression model adjusted for all confounding variables, the odds ratios (95% confidence intervals) for the association between SII/100 and obesity, as well as abdominal obesity, were 1.03 (1.01, 1.06) and 1.04 (1.01, 1.08) respectively. There was a non-linear and reverse U-shaped association between SII/100 and obesity, as well as abdominal obesity, with inflection points at 7.32 and 9.98 respectively. Significant positive correlations were observed before the inflection points, while significant negative correlations were found after the inflection points. There was a statistically significant interaction in the analysis of age, hypertension, and diabetes. Moreover, a notable interaction is observed between SII/100 and abdominal obesity within non-Hispanic Asian populations. CONCLUSIONS: In adults from the United States, there is a positive correlation between SII and the high risk of obesity, as well as abdominal obesity. Further large-scale prospective studies are needed to analyze the role of SII in obesity and abdominal obesity.

Bioelectrical impedance-derived phase angle (PhA) in people living with obesity: Role in sarcopenia and comorbidities.

BACKGROUND AND AIM: Obesity is characterized by alterations in fat and muscle mass. Phase angle (PhA) is considered an index of muscle mass, and is related to comorbidities in SO. This work aimed to assess the relationship between PhA, muscle mass, inflammation, and comorbidities in obesity. METHODS AND RESULTS: We included 198 outpatients with obesity (BMI≥30) divided into tertiles according to PhA distribution (<5°, 5°-6°, >7°). Body composition was analyzed using bioimpedance (Tanita MC-780P Multi-Frequency Segmental Body Composition Analyzer). Quantitative variables were compared using the Kruskal-Wallis test and qualitative variables using the chi-square test. A correspondence analysis was built to show the influence of qualitative variables on subjects in each tertile. Patients in the lowest tertile had the lowest skeletal muscle mass and appendicular skeletal muscle mass index (ASMI); the highest inflammatory index (albumin and derived neutrophil-to-lymphocyte ratio, Alb-dNLR); and the highest percentage of individuals with a history of type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and heart failure (HF). The correspondence analysis showed an association between the lowest tertile and presence of HF with preserved ejection fraction (HFpEF) and CKD. On the logistic regression model, ASMI (OR 0.9, 95%CI 0.85-0.95, p = 0.0004), Alb-dNLR (OR 1.04, 95%CI 1.04-16.4, p = 0.04) and HFpEF and T2DM were significantly associated with the lowest PhA. CONCLUSIONS: Identifying high-risk individuals living with obesity is a priority. These results show that lower PhA is related to inflammation, poorer skeletal muscle mass and consequently, their impact on obesity-related comorbidities and clinical outcomes.

Alleviating effect of chlorogenic acid on oxidative damage caused by hydrogen peroxide in bovine intestinal epithelial cells.

Chlorogenic acid (CGA) is a polyphenol substance contained in many plants, which has good antioxidant activity. This experiment aimed to explore the protective effects of CGA on hydrogen peroxide(H2O2)-induced inflammatory response, apoptosis, and antioxidant capacity of bovine intestinal epithelial cells (BIECs-21) under oxidative stress and its mechanism. The results showed that compared with cells treated with H2O2 alone, CGA pretreatment could improve the viability of BIECs-21. Importantly, Chlorogenic acid pretreatment significantly reduced the formation of malondialdehyde (MDA), lowered reactive oxygen species (ROS) levels, and enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) (P<0.05). In addition, CGA can also improve the intestinal barrier by increasing the abundance of tight junction proteins claudin-1 and occuludin. Meanwhile, CGA can reduce the gene expression levels of pro-inflammatory factors Interleukin-6 (IL-6) and Interleukin-8 (IL-8), increase the expression of anti-inflammatory factor Interleukin-10 (IL-10), promote the expression of the nuclear factor-related factor 2 (Nrf2) signaling pathway, enhance cell antioxidant capacity, and inhibit Nuclear Factor Kappa B (NF-κB) the activation of the signaling pathway reducing the inflammatory response, thereby alleviating inflammation and oxidative stress damage.

Association between Interleukin-6 and Multiple Acute Infarctions in Symptomatic Intracranial Atherosclerotic Disease.

BACKGROUND: Interleukin-6 (IL-6) plays an important role in the pathophysiology of atherosclerosis. This study aimed to determine whether IL-6 is a crucial biomarker associated with Multiple Acute Infarctions (MAIs), which indicate an important stroke mechanism of artery-- to-artery embolism with a high risk of stroke recurrence in symptomatic Intracranial Atherosclerotic Disease (sICAD). We tested the association between circulating IL-6 levels and the presence of MAIs in a prospective population-based registry. METHODS: We included 1,919 patients with sICAD and baseline IL-6 levels from the Third China National Stroke Registry for the current analysis, The baseline IL-6 was centrally measured at Beijing Tiantan Hospital, Images of the brain parenchyma and vascular structures were digitized and then blindly and independently read by two groups of trained readers, The recruited patients were divided into 3 groups according to IL-6 tertiles, The relationship between baseline IL-6 tertile levels and the presence of MAIs was modeled using multivariate logistic regression. RESULTS: Compared to patients in the first IL-6 tertile those in the second and third tertiles demonstrated a significantly higher proportion of MAIs. The odds ratios were 1.81 [95% Confidence Interval (CI), 1.42-2.30] for the second versus first tertile and 2.15 (95% CI 1.66-2.79) for the third versus first tertile, The proportion of patients with MAIs increased with rising IL-6 tertiles observed at 59.3%, 71.6% and 76.4% for the first, second and third tertiles, respectively (P for trend < 0.001). The association between higher IL-6 tertiles and increased proportion of MAIs was also present in subgroups defined by age < 65 years, age ≥ 65 years, male, and high-sensitivity C-reactive Protein (hs-CRP) ≥ 2 mg/L. Furthermore, a significant interaction was detected for the hs- CRP subgroup (P = 0.038). In sensitivity analyses, the positive correlation between IL-6 levels and the proportion of MAIs remained consistent. CONCLUSION: In patients with sICAD, higher IL-6 levels were associated with an increased proportion of MAIs. IL-6 could be used as a biomarker and a potential therapeutic target for future atherosclerosis treatment and prevention in patients with sICAD.

Effect of 17ß-Estradiol on Endothelial Cell Expression of Inflammation-Related MicroRNA.

Introduction/ Objective: Estrogen plays a protective role in vascular health due, in part, to its regulation of endothelial inflammation. However, the mechanism(s) by which estrogen negatively regulates inflammatory signaling pathways is not completely understood. MicroRNAs (miRNAs) are recognized as sensitive and selective regulators of cardiovascular function, inflammation, and disease, yet the effects of 17ß-estradiol on the endothelial miRNA profile are largely unknown. The aim of this study was to determine the effect of 17ß-estradiol on the expression of inflammation-associated miRNAs in endothelial cells in vitro. METHODS: Human Umbilical Vein Endothelial cells (HUVECs) were treated with media in the absence (control) and presence of 17ß-estradiol (100 nM) for 24 hr. Thereafter, endothelial cell release of cytokines (IL-6 and IL-8), the intracellular expression of the central protein inflammatory mediator NF- B, and the levels of inflammatory-associated miRNAs: miR-126, miR-146a, miR-181b, miR-204, and miR-let-7a, were determined. RESULTS: 17ß-estradiol-treated cells released significantly lower levels of IL-6 (47.6±1.5 pg/mL vs 59.3±4.9 pg/mL) and IL-8 (36.3±2.3 pg/mL vs 44.0±2.0 pg/mL). Cellular expression of total NF- B (26.0±2.8 AU vs 21.2±3.1 AU) was not different between groups; however, activated NF- B (Ser536) (12.9±1.7 AU vs 20.2±2.2 AU) was markedly reduced in 17ß-estradiol-treated cells as compared to untreated cells. Furthermore, cellular expressions of miR-126 (1.8±0.3 fold), miR-146a (1.7±0.3 fold), miR-181b (2.1±0.4 fold), miR-204 (1.9±0.4 fold), and miR-Let-7a (1.8±0.3 fold) were markedly increased in response to 17ß-estradiol treatment. CONCLUSION: These data suggest that the anti-inflammatory effect of 17ß-estradiol in endothelial cells may be mediated by miRNAs.

Subcutaneous Injections of Triamcinolone Acetonide for Upper Eyelid Retraction and Swelling Associated with Thyroid Eye Disease: A Retrospective Case Series Study.

Purpose: To evaluate the efficacy of subcutaneous injection of triamcinolone acetonide (SCTA) in treating upper eyelid retraction and swelling in patients with thyroid eye disease (TED). Patients and Methods: This case series included consecutive patients (aged 16-69 years, monitored from June 2012 to December 2015) with TED-related eyelid symptom and without an enlarged extraocular muscle on magnetic resonance imaging (MRI). SCTA (0.5 mL, 40 mg/mL) was administered to target the orbital fat around the levator palpebrae superioris (LPS) muscle. Patients who did not exhibit improvement after the first trial received an additional injection. Follow-up was conducted for 12 months with 3-month intervals. Eyelid retraction, eyelid swelling, and eyelid lag were evaluated at each follow-up visit. Results: In total, 116 eyelids of 102 patients were analyzed. SCTA led to significant improvement in 93% of eyes (108/116), disappearance of eyelid symptoms (74%, 87%, and 73% in retraction, swelling, and lag, respectively), and improvement of scores (from 1.64 to 0.12, 1.32 to 0.26, and 1.72 to 0.30, respectively). Improvement in eyelid symptoms was observed in eight eyes; however, additional steroid therapy was required in these cases due to the emergence of other extraocular muscle inflammation. Additional injection was required in 39.8% of patients. The clinical activity score was lower in the single SCTA group than in the multiple SCTA group (1.5 vs 0.9; p < 0.01). However, the levels of thyroid-stimulating hormone receptor antibody and MRI findings were not significantly different between the two groups. No elevation in intraocular pressure was observed. Eight female patients experienced menstrual disorder. Conclusion: SCTA effectively reduced LPS muscle enlargement and fat tissue swelling in patients with TED. A single SCTA was sufficient in almost 60% of the patients; nevertheless, follow-up is necessary to detect early signs of orbital inflammation even in eyelid-symptom-improved patients.

Recombinant Humanized Collagen Type XVII Promotes Oral Ulcer Healing via Anti-Inflammation and Accelerate Tissue Healing.

Introduction: Recombinant humanized collagen, as a novel biomaterial, exhibits multiple excellent biological functions, such as inhibition of inflammation, promotion of cell proliferation and vascular proliferation, and promotion of tissue healing. However, there is a lack of conclusive evidence regarding the specific role of recombinant humanized collagen type 17 (rhCol 17) in oral ulcer healing. This study explored whether rhCol 17 could promote the proliferation of human gingival fibroblasts (HGFs) and inhibit its inflammation, and whether it could promote the healing of oral ulcers in rats by inhibiting inflammation and accelerating tissue healing. Methods: At the cellular level, we investigated the effect of rhCol 17 on the proliferation of (HGFs) by CCK8; HGFs were mixed with lipopolysaccharide (LPS) to investigate the effect of rhCol 17 on HGFs in an inflammatory state. Eighteen adult male Sprague-Dawley rats were randomly distributed into three groups: blank control group, carbomer group (carbomer sprayed only), and rhCol 17 group (carbomer containing rhCol 17 sprayed), 1 time/day. The samples were collected at D3 and D5. At completion, histological staining and PCR were carried out to study its effect on the healing of oral ulcers in rats. Results: Through cellular experiments, we found that rhCol 17 possesses good biocompatibility and anti-inflammatory properties, and can effectively promote the proliferation and migration of HGFs, as well as significantly reduce the inflammation level of the cells. The animal experimental results showed that rhCol 17 could significantly reduce the inflammation level, promote collagen deposition and angiogenesis at the ulcer site, thus effectively accelerating the healing of oral ulcers in rats. Conclusion: In summary, the collagen sprays containing rhCol 17 have excellent anti-inflammatory effects and could accelerate tissue healing and are expected to provide a new effective treatment for patients with recurrent oral ulcers.

Neurological symphony: post-acute COVID-19 syndrome, an innovative pathophysiological exploration from neuraltherapeutic medicine.

The SARS-CoV-2 pandemic has affected 771 million people and caused 6.9 million confirmed deaths as of November 2023. Beyond the adversity, a crucial and less-explored chapter unfolds: adaptive sequelae. These have altered social, mental, and emotional conditions, leaving an imprint on biological systems. While some cases fully resolve the pathological process post-acute infection, others persist with symptoms, posing a challenge that underscores the need to comprehend pathophysiology from innovative perspectives. The article delves into "Long COVID" or Post-Acute COVID-19 Syndrome (PACS), where symptoms persist for ≥4 weeks irrespective of initial severity. Risk factors include a history of severe illness, in-hospital management, and intensive care. This article also explores theories, derived from various experimental models, that have demonstrated the involvement of the nervous system in coordination with the psychoneuroimmunoendocrine axes in the expression of inflammation. It is posited that PACS involves processes of peripheral and central sensitization (corticalization), facilitating dishomeostasis and the chronicity of the inflammatory process. In this context, various therapeutic strategies grounded in modulating the inflammatory reflex are reviewed, primarily through the infiltration of local anesthetics via linear and non-linear approaches. Neural therapeutic use is considered to stimulate the regulatory inflammatory circuits coordinated by the neuroimmune-endocrine system.

The role of osteopontin and osteocyte-derived factors in secondary hyperparathyroidism-induced myopathy.

Muscle weakness is a common symptom in CKD patients, and the pathway by which secondary hyperparathyroidism (SHPT) affects muscle function is unknown. Osteopontin (OPN), a bone matrix protein stimulated by PTH and phosphate, has been associated with inflammatory muscle diseases. In this observational and prospective cohort study, we evaluated 30 patients with severe SHPT (39 ± 12 yr; 18 women), before and 6 mo after parathyroidectomy (PTx). We examined the relationships among CKD-mineral and bone disorder parameters; myokine and inflammatory cytokine levels; and changes in resting energy expenditure (REE), muscle function, BMD, and muscle-related proteins. At baseline, the patients showed low gene expression of muscle turnover markers and irisin, as well as high protein expression of OPN, transforming growth factor beta (TGF-ß), and fibroblast growth factor 21. Six months after PTx, REE and muscle mass had not changed, but physical performance, muscle strength, and bone mass improved, more so in patients undergoing total PTx. Also, there were reductions in the protein expression of OPN (11 vs 3%, p=.01) and TGF-ß (21 vs 7%, p=.002) in muscle, together with a significant increase in irisin muscular levels (30 vs 35 pg/mg, p=.02). The gain in bone mass and the increase in irisin levels correlated with a reduction in PTH. The levels of interleukin (IL)-1ß, tumor necrosis factor alpha, and IL-17 (markers of myositis) were also lower after PTx. Our data suggest that SHPT plays a role in CKD-induced muscle dysfunction, indirectly, via release of bone-specific proteins, which is partially reverted with PTx.

n-3 PUFA ameliorate functional outcomes following repetitive mTBI in the fat-1 mouse model.

Purpose: Repeated mild traumatic brain injuries (mTBI) are a continuing healthcare concern worldwide, given its potential for enduring adverse neurodegenerative conditions. Past research suggests a potential protective effect of n-3 polyunsaturated fatty acids (PUFA) in experimental models of mTBI. The aim of this study was to investigate whether the neuroprotective benefits of n-3 PUFA persist following repetitive weight drop injury (WDI). Methods: Male fat-1 mice (n = 12), able to endogenously convert n-6 PUFA to n-3 PUFA, and their wild type (WT) counterparts (n = 12) were maintained on a 10% w/w safflower diet. At 9-10 weeks of age, both groups received one mild low-impact WDI on the closed cranium daily, for three consecutive days. Following each WDI, time to righting reflex and seeking behaviour were measured. Neurological recovery, cognitive, motor, and neurobehavioural outcomes were assessed using the Neurological Severity Score (NSS) over 7 days (168 h) post-last WDI. Brains were assessed for cerebral microhemorrhages by Prussian blue and cellular damage by glial fibrillary acidic protein (GFAP) staining. Results: Fat-1 mice exhibited significantly faster righting reflex and seeking behaviour time, and lower mean NSS scores and at all post-WDI time points (p ≤ 0.05) compared to WT mice. Immunohistochemistry showed no significant difference in presence of cerebral microhemorrhage however, fat-1 mice had significantly lower GFAP staining in comparison to WT mice (p ≤ 0.05). Conclusion: n-3 PUFA is effective in restoring cognitive, motor, and behavioural function after repetitive WDI, which may be mediated through reduced cellular damage of the brain.