Longitudinal Study on Changes of Cancer-Related Fatigue in Elderly Patients with Postoperative Chemotherapy for Non-Small Cell Lung Cancer.

BACKGROUND: Cancer-related fatigue (CRF) stands out as one of the most prevalent subjective adverse reactions experienced by patients following chemotherapy, often resulting in unfavorable symptoms for elderly non-small cell lung cancer (NSCLC) patients during chemotherapy. Hence, the aim of this study was to explore the fluctuations in CRF levels among elderly NSCLC patients undergoing chemotherapy. METHODS: This retrospective study involved 400 elderly patients diagnosed with NSCLC. Standardized guidelines were employed to direct patient care following lung cancer surgery (T0), subsequent to the first (T1), second (T2), third (T3), and fourth (T4) cycles of chemotherapy. At various intervals, all patients underwent assessments utilizing the Piper Fatigue Scale, Karnofsky Performance Status (KPS) Scale, Pittsburgh Sleep Quality Index (PSQI) Scale, and Connor-Davidson Resilience Scale. Additionally, serum levels of IL-6 and TNF-α were quantified using enzyme-linked immunosorbent assay (ELISA). RESULTS: Throughout the treatment regimen, patients exhibited a declining trend in CRF, CD-RISC, and KPS scores (p < 0.05, T0 vs T4), whereas the PSQI score demonstrated a notable increase (p < 0.05, T0 vs T4). Furthermore, ELISA results revealed that as treatment advanced, the average levels of inflammatory markers interleukin 6 (IL-6) and tumor necrosis factor (TNF)-α during the T4 period significantly decreased compared to those at T0 (p < 0.05). CONCLUSION: As the number of chemotherapy treatments for elderly NSCLC patients increased, the severity of CRF and the manifestations of sleep disorders were escalated. Additionally, physical function, psychological resilience, as well as IL-6 and TNF-α levels, exhibited a downward trend.

[Detection of molecular affecting sensitivity to local glucocorticoid therapy in oral lichen planus through transcriptome sequencing].

OBJECTIVE: To detect key genes of local glucocorticoid therapy in oral lichen planus (OLP) through transcriptome sequencing. METHODS: The study prospectively enrolled 28 symptomatic patients who visitied Department of Oral Mucosa, Peking University Hospital of Stomatology from November 2019 to March 2023. Topical inunction of 0.1 g/L of dexamethasone was applied for 1 min, 3 times daily for 4 weeks. The patients' signs and pain symptoms were recorded and they were classified as effective group and ineffective group according to the treatment outcome. Their mucosa samples were collected before treatment. After isolating total RNA, transcriptome sequencing was performed. The gene expression data obtained by sequencing were analyzed differently using the DESeq2 package in R software, and the Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was performed on the basis of the hypergeometric distribution algorithm to describe the biological function of differentially expressed genes (DEGs), accordingly detecting sensitivity related molecular affecting therapeutic effect of dexamethasone. RESULTS: After 4 weeks treatment by topical dexamethasone, 13 cases of the 28 OLP patients responding well with the sign score reducing from 7.0 (4.5, 9.0) to 5.0 (3.0, 6.3), pain score decreasing from 5.0 (2.0, 5.5) to 2.0 (0.0, 3.5), oral health impact profile lessening from 5.0 (3.5, 9.0) to 1.0 (0.0, 5.0) significantly (P<0.01) were classified as effective group and 15 cases with poor response to the drug were sorted as ineffective group. There were no significant differences of demographic and baseline levels of clinical features, especially disease severity between these two groups. A total of 499 DEGs including 274 upregulated and 225 downregulated genes were identified between effective group and ineffective group. KEGG enrichment analysis showed that upregulated genes in effective group compared with ineffective group including CLDN8, CTNNA3, MYL2 and MYLPF were associated with leukocyte transendothelial migration, while downregulated genes were significantly enriched in tumor necrosis factor (TNF), interleukin-17 (IL-17), nuclear factor kappa B (NF-κB) signaling pathways, and cortisol synthesis and secretory. CONCLUSION: High expressions of CLDN8, CTNNA3, MYL2 and MYLPF genes in patients with oral lichen planus have a good clinical response to topical dexamethasone, while patients with high expression genes of inflammation pathway such as TNF, IL-17, NF-κB and cortisol synthesis and secretion received poor effect.

Peri-implantitis Diagnosis and Prognosis Using Biomarkers: A Systematic Literature Review.

PURPOSE: To summarize the latest scientific literature regarding the concentrations of biomarkers in saliva and peri-implant crevicular fluid (PICF) of healthy implant (HI) patients and patients with peri-implant mucositis (PIM) and peri-implantitis (PI). MATERIALS AND METHODS: The literature review was performed according to PRISMA guidelines. The databases used were PubMed MEDLINE, ScienceDirect, and Cochrane Library. A combination of keywords was used, and selection criteria were applied. Selected articles were published between February 1, 2017, and February 1, 2022, written in English, conducted in humans, and examined the levels of saliva and PICF biomarkers in PI patients and compared them to HI/PIM patients. RESULTS: A total of 16 publications were selected, involving a total of 1,117 patients with 1,346 implants. Qualitative analysis revealed 49 different biomarkers, the levels of which were compared between groups. After evaluating the most frequently studied biomarkers, significantly higher values of IL-1ß, RANKL, sRANKL, IL-6, TNF-α, TNFSF12, MMP2, and MMP8 levels were observed in the PI group than in the HI group. CONCLUSIONS: Of all 49 biomarkers evaluated, IL-1ß and RANKL have potentially the highest diagnostic significance in the assessment of peri-implant inflammatory conditions, as differences were observed between all three groups (HI < PIM < PI), but data from current publications were not fully sufficient to provide strong evidence.

Preterm Delivery in Obese Mothers Predicts Tumor Necrosis Factor-α Levels in Breast Milk.

Background: Breast milk (BM) is a nutritive fluid that is rich in bioactive components such as hormones and cytokines that can shape the newborn's feeding habits and program the newborn's immature immune system. BM components can change under different scenarios that include maternal body mass index (BMI) and premature birth. This study aimed to study the interaction of premature status or maternal obesity on the hormonal and cytokine profile in BM according to the sex of the offspring. Materials and Methods: We recruited 31 women with preterm births from the Centro de Alta Especialidad Dr. Rafael Lucio in Mexico. Luminex multiplexing assay was used for quantifying cytokine profile of monocyte chemoattractant protein-1, tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)1-ß, IL-2, IL-4, IL-6, IL-7, and hormones insulin, ghrelin, leptin, and glucagon in mature BM samples. Biological modeling was performed to predict the interaction between cytokines and hormones, maternal BMI status, infant birth sex, parity, and gestational age. Results: BM multiplex analysis showed positive correlations for TNF-α and increasing prematurity and for higher maternal BMI and IL-2, IL-4, and IL-6 cytokines. Multiple regression models identified an interaction between maternal BMI and gestational weeks in male infants that is associated to TNF-α accumulation in BM. Biological modeling predicts that preterm delivery in mothers with obesity modulates TNF- α levels in mature BM of women with male offspring. Conclusion: Prematurity and obesity modify BM's immune profile. TNF- α expression increases as prematurity increases, and maternal BMI correlates positively with increases in IL-2, IL-6, and IL-4. Our multiple regression model also shows that maternal BMI and gestational weeks in male infants predict TNF-α.

Obesity Is Associated with a Weakened Gingival Inflammatory Cytokine Response.

Background and Objectives: An obesity-related elevated body mass index (BMI) across life is associated with chronic low-grade inflammation and increased levels of C-reactive protein (CRP) in blood. CRP is a marker and promoter of inflammation. The objectives of this study were to examine the effect of obesity on the relationship between peripheral and gingival CRP levels and to examine the effects of gingival CRP levels on gingival fluid inflammatory cytokines in periodontitis-resistant obese individuals. Materials and Methods: Thirty-nine participants in good periodontal health were recruited. Twenty patients were classified as lean and nineteen as obese based on their BMI levels. A thorough periodontal assessment was carried out. Gingival crevicular fluid (GCF) and blood samples were collected. Both GCF and blood samples were analyzed for interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17A (IL-17A), and CRP. Results: GCF CRP levels were significantly higher in the obese than in the lean individuals. No statistically significant differences were noted between the two groups in either GCF or blood in terms of any of the inflammatory cytokine levels. IL-17A was not detected in the GCF of most subjects in both groups. GCF CRP levels were positively associated with blood CRP levels, and the association tended to be stronger in the obese individuals. GCF CRP showed no associations with GCF IL-10 in both groups. Although GCF CRP levels were positively associated with multiple GCF inflammatory cytokines (e.g., IL-1ß, IL-6, IL-8, and TNF-α) in all subjects, the associations tended to be weaker in the obese individuals (e.g., IL-1ß, IL-6, and TNF-α). Furthermore, the levels of the GCF inflammatory cytokines IL-6 and TNF-α were decreased in the obese individuals. Conclusions: Obesity unfavorably influences the relationship between blood and GCF CRP levels and promotes increased CRP levels in GCF. Collectively, the findings suggest a weakened inflammatory cytokine response in the gingival tissues of obese individuals.

A liquid crystal-based biosensor for sensitive detection of tumor necrosis factor-alpha.

Tumor necrosis factor-alpha (TNF-α) is a cytokine secreted by the macrophages and Th1 cells of the immune system in response to inflammation. Given its significance as a biomarker with elevated levels in physiological fluids in various conditions, there is an increasing demand for a simple and accurate TNF-α detection strategy. In this article, we present a liquid crystal (LC)-based biosensor developed for sensitive TNF-α detection. The biosensor operates as follows: TNF-α and detection antibodies (DAbs) form complexes during preincubation. These complexes then bind with the surface-immobilized capture antibodies (CAbs), facilitating the antigen-antibody reaction between the CAbs and the TNF-α/DAb complexes. This target recognition interaction alters the surface topography, disrupting the vertical orientation of LCs produced by dimethyloctadecyl[3-(trimethoxysilyl)-propyl]ammonium chloride. The orientational change in the LCs can be easily visualized with a polarized optical microscope, resulting in brighter images as TNF-α levels rise. Our results demonstrated a linear range of 5.00-500 pg/mL, with a limit of detection and limit of quantification being 1.08 and 3.56 pg/mL, respectively. Recovery experiments on diluted saliva samples produced reasonable results, with TNF-α recoveries ranging from 97.1% ± 2.58% to 107% ± 5.95%.

Expression of tight junction proteins in smokers and non-smokers with generalized Stage III periodontitis.

OBJECTIVE: This study aims to evaluate the gingival crevicular fluid (GCF) levels of tumor necrosis factor-α (TNF-α), zonula occludens-1 (ZO-1), occludin (Occ), and tricellulin (Tric) in periodontitis, as well as their alterations due to smoking. BACKGROUND: Tight junctions (TJ), which consist of transmembrane and cytoplasmic scaffolding proteins, connect the epithelial cells of the periodontium. Occ, claudins, junctional adhesion molecules, and Tric are transmembrane TJ proteins found at the cell membrane. The transmembrane TJ proteins and the intracellular cytoskeleton are directly linked by cytoplasmic scaffolding proteins such as ZO-1. Although the functions and locations of these molecules have been defined, their behavior in periodontal inflammation is unknown. METHODS: The study included four groups: individuals with periodontal health without smoking (C; n = 31), individuals with generalized Stage III periodontitis without smoking (P; n = 28), individuals with periodontal health while smoking (CS; n = 22), and individuals with generalized Stage III periodontitis while smoking (PS; n = 18). Clinical periodontal parameters were recorded, and enzyme-linked immunosorbent assay (ELISA) was used to examine ZO-1, Occ, Tric, and TNF-α levels in GCF. RESULTS: In the periodontitis groups, clinical parameters were significantly higher (p < .001). The site-specific levels of TNF-α, ZO-1, Tric, and Occ in the P group were statistically higher than those in the other groups (p < .05). TNF-α, probing pocket depth (PPD), and bleeding on probing (BOP) exhibited positive correlations with all TJ proteins (p < .005). CONCLUSIONS: Smoking could potentially affect the levels of epithelial TJ proteins in the GCF, thereby potentially playing a significant role in the pathogenesis of the periodontal disease.

The efficacy of hydrogel containing zinc oxide-loaded and minocycline serum albumin nanopartical in the treatment of peri-implantitis

Background: We conducted this animal study to assess the efficacy of the novel hydrogel containing zinc oxide-loaded and minocycline serum albumin nanoparticals (Mino-ZnO@Alb NPs) on peri-implantitis in an experimental mouse model. Material and methods: Mino-ZnO@Alb NPs was prepared as previously reported. The peri-implantitis model was successfully established in rats, and the rats were divided into three groups randomly: Mino-ZnO@Alb NPs (Mino-ZnO) group, minocycline group, and untreated group. Four weeks later, clinical and radiographic assessments were performed to evaluate soft tissue inflammation and bone resorption level. Histologic analysis was performed to estimate the amount of remaining supporting bone tissue (SBT) around implants. ELISA tests were used to determine the concentration of inflammation factor interleukin-1-beta (IL-1β) and anti-inflammation factor tumor necrosis factor-alpha (TNF-α) around implants. Results: After one month, the Mino-ZnO group showed better results than the other two groups in regards to the results of bleeding on probing, probing pocket depth, bleeding index and gingival index. X-ray showed that SBT at mesial and distal sites around implants in the other two groups was significantly lower compared with that of Mino-ZnO group. The quantity of osteoclasts in peri-implant tissues of the Mino-ZnO group was less than that in the minocycline and untreated groups. IL-1β in the Mino-ZnO group was lower than that in the other two groups. TNF-α level was the opposite. Conclusions: Mino-ZnO@Alb NPs can effectively treat peri-implantitis and promote soft tissue healing, and may act as a promising product. (AU)

Evaluation of biocompatibility and angiogenic potential of extracellular matrix hydrogel biofunctionalized with the LL-37 peptide.

BACKGROUND: Biomaterials must allow revascularization for a successful tissue regeneration process. Biomaterials formulated from the extracellular matrix (ECM) have gained popularity in tissue engineering because of their superior biocompatibility, and due to their rheological properties, ECM-hydrogels can be easily applied in damaged areas, allowing cell colonization and integration into the host tissue. Porcine urinary bladder ECM (pUBM) retains functional signaling and structural proteins, being an excellent option in regenerative medicine. Even some small molecules, such as the antimicrobial cathelicidin-derived LL-37 peptide have proven angiogenic properties. OBJECTIVE: The objective of this study was to evaluate the biocompatibility and angiogenic potential of an ECM-hydrogel derived from the porcine urinary bladder (pUBMh) biofunctionalized with the LL-37 peptide (pUBMh/LL37). METHODS: Macrophages, fibroblasts, and adipose tissue-derived mesenchymal stem cells (AD-MSC) were exposed pUBMh/LL37, and the effect on cell proliferation was evaluated by MTT assay, cytotoxicity by quantification of lactate dehydrogenase release and the Live/Dead Cell Imaging assays. Moreover, macrophage production of IL-6, IL-10, IL-12p70, MCP-1, INF-γ, and TNF-α cytokines was quantified using a bead-based cytometric array. pUBMh/LL37 was implanted directly by dorsal subcutaneous injection in Wistar rats for 24 h to evaluate biocompatibility, and pUBMh/LL37-loaded angioreactors were implanted for 21 days for evaluation of angiogenesis. RESULTS: We found that pUBMh/LL37 did not affect cell proliferation and is cytocompatible to all tested cell lines but induces the production of TNF-α and MCP-1 in macrophages. In vivo, this ECM-hydrogel induces fibroblast-like cell recruitment within the material, without tissue damage or inflammation at 48 h. Interestingly, tissue remodeling with vasculature inside angioreactors was seen at 21 days. CONCLUSIONS: Our results showed that pUBMh/LL37 is cytologically compatible, and induces angiogenesis in vivo, showing potential for tissue regeneration therapies.

The efficacy of hydrogel containing zinc oxide-loaded and minocycline serum albumin nanopartical in the treatment of peri-implantitis.

BACKGROUND: We conducted this animal study to assess the efficacy of the novel hydrogel containing zinc oxide-loaded and minocycline serum albumin nanoparticals (Mino-ZnO@Alb NPs) on peri-implantitis in an experimental mouse model. MATERIAL AND METHODS: Mino-ZnO@Alb NPs was prepared as previously reported. The peri-implantitis model was successfully established in rats, and the rats were divided into three groups randomly: Mino-ZnO@Alb NPs (Mino-ZnO) group, minocycline group, and untreated group. Four weeks later, clinical and radiographic assessments were performed to evaluate soft tissue inflammation and bone resorption level. Histologic analysis was performed to estimate the amount of remaining supporting bone tissue (SBT) around implants. ELISA tests were used to determine the concentration of inflammation factor interleukin-1-beta (IL-1ß) and anti-inflammation factor tumor necrosis factor-alpha (TNF-α) around implants. RESULTS: After one month, the Mino-ZnO group showed better results than the other two groups in regards to the results of bleeding on probing, probing pocket depth, bleeding index and gingival index. X-ray showed that SBT at mesial and distal sites around implants in the other two groups was significantly lower compared with that of Mino-ZnO group. The quantity of osteoclasts in peri-implant tissues of the Mino-ZnO group was less than that in the minocycline and untreated groups. IL-1ß in the Mino-ZnO group was lower than that in the other two groups. TNF-α level was the opposite. CONCLUSIONS: Mino-ZnO@Alb NPs can effectively treat peri-implantitis and promote soft tissue healing, and may act as a promising product.

TNF-α and OSX mRNA of Salivary Small Extracellular Vesicles in Periodontitis: A Pilot Study.

This cross-sectional pilot study explored extracellular vesicle (EV)-derived gene expression of markers for bone turnover and pro-inflammatory cytokines in periodontal disease. Whole unstimulated saliva was collected from 52 participants (18 healthy, 13 gingivitis, and 21 stages III/IV periodontitis), from which salivary small extracellular vesicles (sEVs) were enriched using the size-exclusion chromatography method, and characterized by morphology, EV-protein, and size distribution, using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), and Nanoparticle Tracking Analysis (NTA), respectively. Bone turnover markers and pro-inflammatory cytokines in salivary sEVs were evaluated using reverse transcription PCR. Salivary sEVs morphology, mode, size distribution, and particle concentration were comparable between healthy, gingivitis, and periodontitis patients. The CD9+ subpopulation was significantly higher in periodontitis-derived salivary sEVs compared with healthy. The detection of sEVs mRNA for osterix and tumor necrosis factor-alpha was significantly decreased and increased, respectively, in periodontitis compared with healthy controls, with good discriminatory power for periodontitis diagnosis (area under the curve >0.72). This pilot study demonstrated that salivary sEVs mRNAs may serve as a potential noninvasive biomarker source for periodontitis diagnosis.

Volatile profiling coupled with multivariate analysis, antiproliferative and anti-inflammatory activities of rhizome essential oil of four Hedychium species from India.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Hedychium of family Zingiberaceae comprises several perennial rhizomatous species widely used in perfumery and traditional folk medicine to treat diseases related to asthma, diarrhoea, nausea, stomach disorders, inflammation and tumours. Several species of Hedychium have remained under-explored with respect to their chemical composition and biological activities. AIM OF THE STUDY: The current research aimed to explore the chemical composition and evaluate the antiproliferative and anti-inflammatory activities of rhizome essential oil from four Hedychium species (H. coccineum, H. gardnerianum, H. greenii and H. griffithianum). MATERIALS AND METHODS: Compound identification was accomplished using a Clarus 580 gas chromatography system in conjunction with mass spectrometry (GC-MS). The multivariate data statistics using chemometrics (PCA, PLS-DA, sPLS-DA) and cluster analysis (Dendrogram, Heat maps, K-means) were used to compare the similarity and relationship among Hedychium metabolomes. MTT assay was employed to visualize the antiproliferative property against MCF7, HepG2 and PC3 cancerous cell lines. The toxicity of essential oils was determined using 3T3-L1 non-tumorigenic/normal cells. Lipopolysaccharide (LPS)-induced RAW 264.7 cells were used to investigate the anti-inflammatory properties of Hedychium essential oils by measuring the production of nitric oxide (NO) using the Griess reagent method. Furthermore, the levels of prostaglandin (PGE2) and pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) was assessed using the ELISA technique. RESULTS: In total, 82 compounds were identified in four targeted species of Hedychium from which 1,8-cineole (52.71%), ß-pinene (32.83%), α-pinene (19.62%), humulene epoxide II (19.86%) and humulene epoxide I (19.10%) were the major constituents. Monoterpenes (8.5-59.9%) and sesquiterpenes (2.87-54.11%) were the two class of compounds, found as the most prevalent in the extracted essential oils. The multivariate analysis classified the four Hedychium species into three different clusters. Hedychium essential oils exhibited potent antiproliferative activity against MCF7, HepG2 and PC3 cancer cell lines with IC50 values less than 150 µg/mL where H. gardnerianum exhibited the highest selective cytotoxicity against human breast and prostate adenocarcinoma cells with an IC50 value of 44.04 ± 1.07 µg/mL and 56.11 ± 1.44 µg/mL, respectively. The essential oils on normal (3T3-L1) cells displayed no toxicity with higher IC50 values thereby concluding as safe to use for normal human health without causing any side effects. Besides, the essential oils at 100 µg/mL concentration revealed remarkable anti-inflammatory activity in LPS-activated RAW 264.7 murine macrophages by inhibiting the production of inflammatory mediators, with H. greenii exhibiting the maximum anti-inflammation response by significantly suppressing the levels of NO (84%), PGE2 (87%), TNF-α (94.3%), IL-6 (95%) and IL-1ß (85%) as compared to LPS treated group. CONCLUSION: The present findings revealed that the Hedychium species traditionally used in therapeutics could be a potential source of active compounds with antiproliferative and anti-inflammatory properties.

The Impact of Non-Andrological Medications on Semen Characteristics, Oxidative Stress and Inflammatory Parameters.

Background and Objectives: The aim of this study was to evaluate the impact of medications on oxidative stress, inflammatory biomarkers and semen characteristics in males with idiopathic infertility. Materials and Methods: In this observational case-control clinical study, 50 men with idiopathic infertility were enrolled, of whom 38 (the study group) were on pharmacological treatment and 12 made up the control group. The study group was clustered according to the medications (Group A: anti-hypertensive, n = 10; Group B: thyroxine, n = 6; Group C: non-steroidal anti-inflammatory drugs, n = 13; Group D: miscellaneous, n = 6; Group E: lipid-lowering drugs, n = 4). Semen analyses were performed according to WHO 2010 guidelines. Interleukins (IL)-10, IL-1 beta, IL-4, IL-6, Tumor Necrosis Factor- alpha (TNF-alpha) and IL-1 alpha were determined using a solid-phase sandwich immunoassay. The diacron reactive oxygen metabolites, d-ROMs test, was performed by means of a colorimetric determination of reactive oxygen metabolites and measured with a spectrophotometer. Beta-2-microglobulin and cystatin-C were measured with an immunoturbidimetric analyzer. Results: No differences between the study and control groups for age and macroscopic and microscopic semen characteristics were found, nor were any differences found after clustering according to the drug categories. IL-1 alpha and IL-10 were significantly lower in the study group compared with the control group; IL-10 was significantly lower in groups A, B, C and D compared with the control group. Furthermore, a direct correlation between IL-1 alpha, IL-10 and TNF-alpha and leukocytes was found. Conclusions: Despite the sample size limitations, the data suggest a correlation between drug use and activation of the inflammatory response. This could clarify the pathogenic mechanism of action for several pharmacological classes on male infertility.

1-Tetracosanol isolated from the leaves of Eupatorium glandulosum, accelerates wound healing by expressing inflammatory cytokines and matrix metalloproteinase.

ETHNOPHARMACOLOGICAL RELEVANCE: The leave paste of the plant, Eupatorium glandulosum H. B & K, has been traditionally used to treat cuts and wounds by the tribal community of the Nilgiris district of Tamilnadu, India. AIM OF THE STUDY: The present study was carried out to investigate the wound healing potential of this plant extract and the compound, 1-Tetracosanol, isolated from the ethyl acetate fraction. MATERIALS AND METHODS: An in vitro study was designed to compare the viability, migration and apoptosis of the fresh methanolic extract fractions and 1-Tetracosanol using mouse fibroblast NIH3T3 cell lines and human keratinocytes HaCaT cell lines, respectively. 1-Tetracosanol was evaluated for its viability, migration, qPCR analysis, in silico, in vitro and in vivo. RESULTS: 1-Tetracosanol at the concentration of 800, 1600, 3200 µM has significant wound closure of 99% at 24 h. The compound when screened in silico against various wound healing markers, TNF-α, IL-12, IL-18, GM-CSF and MMP-9, revealed high binding energy of -5, 4.9 and -6.4 kcal/mol for TNF-α, IL-18 and MMP-9, respectively. Gene expression and the release of cytokines increased at an early stage of the wound repair. 1-Tetracosanol, at 2% gel showed 97.35 ± 2.06% wound closure at 21st day. CONCLUSION: 1-Tetracosanol is a good lead for drug development targeted towards wound healing activity and work in this direction is in progress.

Autoantibodies of inflammatory cytokines as serum biomarkers in OSA patients.

As many as 90% of patients with obstructive sleep apnea (OSA) may be undiagnosed. It is necessary to explore the potential value of autoantibodies against CRP, IL-6, IL-8 and TNF-α in the diagnosis of OSA. ELISA was performed to detect the level of autoantibodies against CRP, IL-6, IL-8 and TNF-α in sera from 264 OSA patients and 231 normal controls (NCs). The expression level of autoantibodies against CRP, IL-6 and IL-8 in OSA were significantly higher than that in NC while the level of anti-TNF-α was lower in OSA than that in NC. The per SD increment of anti-CRP, anti-IL-6 and anti-IL-8 autoantibodies were significantly associated with a 430%, 100% and 31% higher risk for OSA, respectively. The AUC of anti-CRP was 0.808 (95% CI: 0.771-0.845) when comparing OSA with NC, while the AUC increased to 0.876 (95% CI: 0.846-0.906) combining four autoantibodies. For discrimination of severe OSA versus NC and non-severe OSA versus NC, the AUC for four autoantibodies combination was 0.885 (95% CI: 0.851-0.918) and 0.876 (95% CI: 0.842-0.913). This study revealed the association between autoantibodies against inflammatory factors and OSA, and the combination of autoantibodies against CRP, IL-6, IL-8 and TNF-α may function as novel biomarker for monitoring the presence of OSA.

Gingival crevicular fluid periodontal ligament-associated protein-1, sclerostin, and tumor necrosis factor-alpha levels in periodontitis.

BACKGROUND: In periodontitis, the equilibrium between bone formation and resorption skews in favor of bone loss. Periodontal ligament-associated protein-1 (PLAP-1) and sclerostin play a significant role in the suppression of bone formation. Tumor necrosis factor-alpha (TNF-α) is a central proinflammatory cytokine related to periodontal bone loss. This study aims to assess gingival crevicular fluid (GCF) PLAP-1, sclerostin, and TNF-α levels in individuals with periodontal disease. METHODS: Seventy-one individuals diagnosed with generalized stage III grade C periodontitis (n = 23), gingivitis (n = 24), and periodontal health (n = 24) were included in the study. Full-mouth clinical periodontal measurements were performed. PLAP-1, sclerostin, and TNF-α total amounts in GCF were quantified by ELISA. Nonparametric methods were used for the data analyses. RESULTS: Periodontitis group exhibited significantly higher GCF PLAP-1, sclerostin and TNF-α levels compared with gingivitis and periodontally healthy groups (p < 0.05). GCF PLAP-1 and TNF-α levels of gingivitis group were higher than healthy controls (p < 0.05) whereas GCF sclerostin levels were similar in two groups (p > 0.05). Significant positive correlations were found between GCF PLAP-1, sclerostin and TNF-α levels and all clinical parameters (p < 0.01). CONCLUSIONS: To our knowledge, this is the first study showing GCF PLAP-1 levels in periodontal health and disease. Increased GCF PLAP-1 and sclerostin levels and their correlations with TNF-α in periodontitis imply that those molecules might be involved in the pathogenesis of periodontal disease. Further studies in larger mixed cohorts are needed to enlighten the possible role of PLAP-1 and sclerostin in periodontal bone loss.

Association between Caspase-1, TNF-α Salivary Level and Their Diagnostic Potential to Discriminate Periodontitis from Healthy Control.

PURPOSE: Periodontitis is associated with caspase and proinflammatory mediators, such as caspase-1 and tumor necrosis factor-alpha (TNF-α). The aim of this study was to evaluate the salivary levels of caspase-1 and TNF-α and determine their accuracy in differentiating periodontitis patients from individuals with a healthy periodontium. MATERIALS AND METHODS: This case-control study enrolled 90 subjects, aged 30 to 55, attending the Department of Periodontics at Baghdad's outpatient clinic. Patients were initially screened to evaluate their eligibility for recruitment. After applying inclusion/exclusion criteria, subjects with a healthy periodontium were included in group 1 (controls), while subjects with periodontitis were included in group 2 (patients). The salivary levels of caspase-1 and TNF-α in participants' unstimulated saliva were measured using an enzyme-linked immunosorbent assay (ELISA). Then the periodontal status was determined using the following indices: full-mouth plaque, full-mouth bleeding on probing, probing pocket depth, clinical attachment level, and gingival recession. RESULTS: TNF-α and caspase-1 salivary levels were higher in periodontitis patients than in healthy controls and were positively correlated with all clinical parameters. A positive significant correlation between TNF-α and caspase-1 salivary levels was noticed. For differentiating periodontal health and periodontitis, the area under the curve (AUC) values of TNF-α and caspase-1 were 0.978 and 0.998, while the proposed cut-off points were 128.163 pg/ml and 1.626 ng/ml, respectively. CONCLUSION: The present findings supported a previous discovery that periodontitis patients have significantly higher levels of salivary TNF-α. In addition, there was a positive correlation between the salivary levels of TNF-α and caspase-1. Furthermore, caspase-1 and TNF-α showed high sensitivity and specificity in the diagnosis of periodontitis, as well as distinguishing periodontitis from periodontal health.

Structural characterization of a heteropolysaccharide from the fruit of Crataegus pinnatifida and its bioactivity on the gut microbiota of immunocompromised mice.

Crataegus pinnatifida is a common food in China, Europe and North America. In order to confirm polysaccharide was the material basis for C. pinnatifida to exert immune regulation. A polysaccharide (CPP) with a molecular weight of 13.58 kDa was isolated from C. pinnatifida. The structure of CPP was determined to be a backbone composed of â†’ 3,5)-α-l-Araf-(1→, with two branches consisting of â†’ 4)-α-d-Galp-(1 â†’ and â†’ 5)-α-l-Araf-(1→, with α-l-Araf and α-d-Manp as the terminal unit. CPP (10 âˆ¼ 500 µg/mL) could promote the secretion of nitric oxide, interleukin-2, interleukin-6 and tumor necrosis factor-α in vitro. CPP could significantly restore the body weight of immunosuppressive mice and improve the immune organ index and interleukin-2, interleukin-6, and tumor necrosis factor-α secretion. In addition, CPP increased the abundance of Bacteroidetes and Verrucomicrobia and decreased the abundance of Proteobacteria at the phylum level. So CPP can regulate the gut microbiota and play an important role in immune regulation.

Clinical features and influencing factors of curative effect in children with acute laryngitis and laryngeal obstruction.

OBJECTIVE: We aim to explore the clinical features and influencing factors of curative effect in children harboring acute laryngitis with laryngeal obstruction. METHODS: There involved 237 children with acute laryngitis and 80 healthy children who required physical examination in our hospital between January and September in 2021. The healthy children who required physical examination were allocated into the healthy/control group. The clinical data and laboratory indexes of each group were compared. We also analyzed the risk factors for curative effect of acute laryngitis with laryngeal obstruction among children using univariate/multivariate logistic regression. RESULTS: The incidence of barking cough, sore throat, dryness, pruritus, dyspnea, diffuse congestion and swelling of laryngeal mucosa and vocal cord congestion or covered with vascular striation in degree III laryngeal obstruction group were significantly higher than other study groups, with degree II laryngeal obstruction group higher than degree I group, and degree I group higher than no laryngeal obstruction group (P<0.05). Moreover, the levels of CRP, TNF-α, IL-6, IL-8 and WBC in degree III laryngeal obstruction group were higher than other three study groups, with degree II higher than degree I laryngeal obstruction group and no obstruction group, and degree I higher than no laryngeal obstruction group (P<0.05). Multivariate logistic regression analysis showed that CRP, TNF-α, IL-6 and IL-8 were the risk factors affecting the curative effect of acute laryngitis with laryngeal obstruction in children, and the differences were statistically significant (P<0.05). CONCLUSION: The study revealed the incidence of barking cough, sore throat, dryness, pruritus, dyspnea, diffuse congestion and swelling of laryngeal mucosa vocal cord congestion or covered with vascular striation is highly associated with the severity of acute laryngitis with laryngeal obstruction in children. Additionally, higher levels of CRP, TNF-α, IL-6, IL-8 and WBC indicated serious condition of the disease among children. Hence the risk factors responsible for the efficacy of acute laryngitis in children are CRP, TNF-α, IL-6 and IL-8.

Baseline interleukin-10, CD163, and tumor necrosis factor-like weak inducer of apoptosis (TWEAK) gingival tissue levels in relation to clinical periodontal treatment outcomes: A 12-week follow-up study.

BACKGROUND: The aim of this study was to examine the relationship between healing response after non-surgical periodontal treatment and baseline gingival tissue levels of M2 macrophage activation-related proteins CD163, interleukin (IL)-10, interferon (IFN)-γ, and tumor necrosis factor-like weak inducer of apoptosis (TWEAK), and the CD163/TWEAK ratio. METHODS: Eighty-eight gingival tissue samples from 44 Stage III/IV, Grade C periodontitis patients (18 smokers) and 41 tissue samples from 41 periodontally healthy participants (18 smokers) were evaluated. Clinical parameters were recorded in periodontally healthy individuals at baseline and in periodontitis patients at pre-treatment and 2, 6, and 12 weeks following therapy. IL-10, IFN-γ, CD163, and TWEAK levels were analyzed with Luminex technique. RESULTS: Tissue levels (median, 1st -3rd quartile) of IL-10 (pg/ng protein), CD163 (pg/µg protein) and TWEAK (pg/µg protein) were as follows: IL-10 periodontitis: 2.08, 0.86-5.32 and periodontally healthy: 5.22, 3.20-10.25; CD163 periodontitis: 8.85, 4.92-14.06 and periodontally healthy: 18.36, 12.51-34.02; TWEAK periodontitis: 0.08, 0.05-0.11 and periodontally healthy: 0.16, 0.12-0.21. IL-10, CD163, and TWEAK levels were higher (P < 0.001) in periodontally healthy tissues than in periodontitis tissues. Pocket closure at 12 weeks was associated with elevated baseline gingival CD163 levels (P = 0.047) and CD163/TWEAK ratio (P = 0.001). Elevated baseline gingival CD163/TWEAK ratio was associated with pocket reduction at 6 (P = 0.022) and 12 weeks (P = 0.002). CONCLUSION: Associations of pocket closure with pre-treatment gingival tissue CD163 levels and CD163/TWEAK ratio indicate that baseline M2 macrophage activation profile may play a role in periodontal wound healing.