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In this paper, we report on the electrical impedance measurement of human endothelial cellular networks and show the existence of emergent power law behavior in its admittance. In particular, we find that the admittance scales with the frequency ω as ωα, with the exponent that varies with the degree of the disruption caused by the inflammation in the endothelial cellular network. We demonstrate that the power law of the measured electrical admittance can be understood by a simple percolation model of a large R–C (resistor–capacitor) network, which allows us to relate quantitatively and the intensity of inflammation. Our results suggest that the electrical properties of heterogeneous biomaterials, like living tissues, behave as a complex microstructural network. [ABSTRACT FROM AUTHOR]

Background: Several studies have revealed the positive healthy impacts of branched-chain fatty acids (BCFAs). However, most of these studies evaluated the serum BCFAs in humans, or treatment with exogenous BCFAs in animal or in-vitro models and the health impacts of dietary BCFAs have not yet been studied. Due to positive effects of BCFAs in sport, in the current study, we aimed to investigate the association between dietary BCFAs and metabolic and inflammatory parameters among elite and subelite soccer players. Methods: A cross-sectional study was carried out among 335 elite and subelite soccer players (196 male), aged between 20 and 45 years old. Soccer players were enrolled from 32 teams under the directive of The Chinese Football Association. Demographic, anthropometric, and dietary assessments were performed and laboratory measurement including serum lipids, glycemic markers, and high-sensitivity C-reactive protein was measured. Results: Those with the highest dietary BCFAs consumption had higher appetite (p =.009). Also, high consumption of dietary BCFAs was associated with lower diastolic blood pressure (odds ratio: 0.958; confidence interval: 0.918–0.999; p =.046) and low high-sensitivity C-reactive protein concentrations in the third tertile of dietary BCFAs (odds ratio: 0.431; confidence interval: 0.300–0.618; p <.001). No other association between biochemical variables and dietary BCFAs was found. Conclusion: As shown in the current study, higher dietary BCFAs consumption was associated with lower diastolic blood pressure and inflammation. Due to very limited number of studies, further studies are needed to have a better perspective of these associations and their underlying mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate four decontamination strategies utilizing enzymatic agents available in most clinical settings to determine (1) the amount of biomaterial that can be removed in a group of previously used healing abutments (uHAs) and (2) the degree to which the decontaminated HAs are capable of inducing an inflammatory response in vitro compared to new HAs. Materials and Methods: In total, 50 HAs were collected following 2 to 4 weeks of intraoral use and distributed randomly into five test groups (groups A-E; n = 10 per group). Group A used enzymatic cleaner foam and an autoclave. Group B used an ultrasonic bath with enzymatic cleaner and an autoclave. Group C used a prophy jet, enzymatic cleaner foam, and an autoclave. Group D used a prophy jet, an ultrasonic bath with enzymatic cleaner, and an autoclave. Lastly, group E used a prophy jet and an autoclave. The control group consisted of 10 new and sterile HAs. Residual protein concentration was determined by a Micro BCA protein assay (Thermo Fisher Scientific), while HAs from each group were stained with Phloxine B and macroscopically examined for the presence of debris. To examine the inflammatory potential, human primary macrophages were exposed to HAs, and supernatant levels of nine cytokine and chemokine profiles were analyzed using a multiplex bead assay. Results: All test groups showed differences in the degree of visual decontamination compared to controls. Groups D and E displayed the most effective surface debris removal and reduced protein concentration, while group A was the least effective. However, compared to controls, all test groups showed high levels of inflammatory cytokine secretion via multiplex assay for up to 5 days. Conclusions: Our study found that decontamination of uHAs utilizing enzymatic cleaners failed to reestablish inert HA surfaces and prevent an inflammatory immune response in vitro. Clinicians should not reuse HAs even after attempts to decontaminate and sterilize HA surfaces. [ABSTRACT FROM AUTHOR]

Background: To evaluate the influence of previous physical activity (PA) during childhood, adolescence, and current PA practice on the production of antibodies and inflammatory response between the first and second doses of the COVID-19 vaccine. Methods: Fifty-nine men and 56 women were evaluated before the first vaccine, and 12 weeks later, blood samples were taken to quantify production of anti-severe acute respiratory syndrome coronavirus-2 immunoglobulin G antibodies and cytokines. Previous PA during childhood and adolescence was self-referred, and current PA was assessed using the International Physical Activity Questionnaire. Results: A positive and significant association was observed only between PA practice during adolescence and an increase in antibody production in adulthood (β = 2012.077, 95% confidence interval, 257.7953–3766.358, P =.025). Individuals who practiced PA during adolescence showed higher production of antibodies between the first and second vaccine dose compared to nonpractitioners (P =.025) and those that accumulated ≥150 minutes per week of current moderate–vigorous PA (MVPA), and presented higher antibody production in relation to who did <150 minutes per week of MVPA (P =.046). Individuals that were practitioners during childhood produced higher G-CSF (P =.047), and those that accumulated ≥150 minutes per week of current MVPA demonstrated lower IP-10 levels (P =.033). However, PA practitioners during adolescence presented higher G-CSF (P =.025), IL-17 (P =.038), IL-1RA (P =.005), IL-1β (P =.020), and IL-2 (P =.026) levels. Conclusion: Our results suggest that adults that accumulated at least 150 minutes of MVPA per week or practiced PA during adolescence developed an improved immune and inflammatory response against COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Objectives: This study examined the impact of injectable plateletrich fibrin (iPRF) and concentrated growth factor on postoperative pain, edema, trismus, and quality of life in impacted mandibular third molar surgery. The primary aim of this study was to minimize common sequelae following third molar surgery by using iPRF and concentrated growth factor. The secondary objective was to compare the postoperative effects of these products. Method and materials: This study represents a single-center, randomized prospective clinical trial conducted at the Ordu University Faculty of Dentistry. It involved patients who underwent third molar surgery for various reasons between July and October 2022. The predictor variables were the use of concentrated growth factor and i-PRF. They were categorized as concentrated growth factor, i-PRF, and control groups. The outcome variables include pain levels and analgesic consumption measured on a visual analog scale, distances between predetermined anatomical points, maximum mouth opening capacity, and data from the postoperative symptom severity (PoSSe) scale. Some statistical tests were performed with a 95% confidence interval, which was considered significant. Results: Total analgesic use was notably lower in the concentrated growth factor group (P = .044). Concentrated growth factor and iPRF outperformed the control group in all edema measurements by postoperative day 7 (tragus–pogonion, lateral canthus–angulus, tragus–commissura; P < .05). Concentrated growth factor significantly reduced trismus on days 2 and 7. Quality of life was notably higher in the concentrated growth factor group than in the control group (P = .026), although iPRF group differences were not significant. Conclusion: The results indicate that concentrated growth factor has a limited impact on postoperative pain, but significantly reduces edema, trismus, and enhances quality of life. The iPRF group experienced positive effects on pain, edema, and trismus, although the statistically significant differences observed with concentrated growth factor highlight its potential for use instead of iPRF after third molar surgery. An increased sample size is essential for more comprehensive results [ABSTRACT FROM AUTHOR]

Objective: Polycystic ovary syndrome (PCOS) is widely reported among young females, and anti-androgens are used for treating hirsutism and acne in these patients. The protective effects of myo-inositol, oral contraceptives, and insulin sensitizers have been reported on the periodontium and high-sensitivity C-reactive protein (hsCRP) levels in PCOS females. However, cyproterone acetate/ethinyl estradiol (CPA/EE) has not yet been studied. This cross-sectional study explores the periodontal status and systemic inflammation in PCOS women on CPA/EE drug combination compared to females not on medication. Method and materials: A total of 150 participants were enrolled into three groups: 50 newly diagnosed PCOS females not on medication (N-PCOS); 50 PCOS females consuming CPA/EE combination for the last 6 months (PCOS+CPA/EE); and 50 systemically healthy females (control group). Anthropometric, biochemical, periodontal parameters, and health-related quality of life questionnaires were recorded. Results: N-PCOS and PCOS+CPA/EE groups showed a nonsignificant difference in hsCRP levels, Gingival Index, bleeding on probing, waist circumference, and waist-hip ratio (P > .05). Gingival thickness and keratinized tissue width were significantly greater in the PCOS+CPA/EE than the N-PCOS group (P = .05); however, these were comparable with the control group (P > .05). Regression analysis showed significant association of bleeding on probing with Gingival Index, clinical attachment level, and hsCRP (P = .05). Conclusions: CPA/EE combination does not influence the periodontal and systemic inflammatory status in PCOS females, as similar levels of local and systemic inflammation were observed in CPA/EE consumers compared with PCOS females not on medication. However, it might play a role in increasing gingival thickness and keratinized tissue width in these patients. [ABSTRACT FROM AUTHOR]

The socket shield technique has been proposed as a surgical method to prevent the collapse of the buccal plate following tooth extraction, leading to excellent soft tissue stability and long-term esthetic outcomes. Despite its success, this technique is still not without potential risks. One of the most common complications is internal exposure of the socket shield, which can present as inner soft tissue inflammation with or without exposure of a portion of the shield. This case series discusses this complication's etiology, diagnosis, treatment, management, and prevention. Data from 10 patients with 12 internally exposed sites are presented. [ABSTRACT FROM AUTHOR]

Objectives: Inflammatory disorders including periodontitis have been investigated for their impact on systemic inflammation and bone health. The present study was conducted with an aim to evaluate impact of control of periodontal inflammation through subgingival instrumentation on serum interleukin 6 and serum C-terminal telopeptide of type I collagen (CTX) in premenopausal females with stage II and III periodontitis. Method and materials: In this single-arm prospective study, periodontal parameters, serum interleukin 6, serum CTX, and hematologic parameters (total leukocyte count, differential leukocyte count, platelet count, mean platelet volume, and platelet distribution width) were assessed at baseline. Subgingival instrumentation was done, and oral hygiene instructions were given. At week 4, professional plaque control was performed, and oral hygiene instructions were reinforced. Serum and hematologic parameters were reassessed at 8 weeks after subgingival instrumentation, in individuals meeting the clinical endpoints (ie, bleeding on probing < 10%). Results: There was significant reduction in serum interleukin 6 of 0.168 ± 0.164 pg/mL (P = .000), and serum CTX of 17.459 ± 4.363 pg/mL (P = .000) at 8 weeks after subgingival instrumentation. There was significant decrease in eosinophil count (P = .018) and mean platelet volume (P = .016) at 8 weeks after subgingival instrumentation; however, no significant change was found in other hematologic parameters. Conclusion: Following subgingival instrumentation, biomarkers of both systemic inflammation (interleukin 6) and bone turnover (CTX) were observed to reduce significantly. This finding hints towards a positive impact of periodontal intervention on bone health. [ABSTRACT FROM AUTHOR]

Purpose: To review experimental peri-implantitis studies using rat models and summarize different peri-implantitis induction techniques and evaluate their effectiveness. Materials and Methods: Electronic searches were conducted by two independent examiners to address the following issues. Meta-analyses explored the marginal bone loss (MBL) of four types of peri-implantitis induction methods in rats. The detailed induction tactics--such as the implant design, implant size, surgical process, time cost, induction methods, and endpoint measurements--were summarized. Results: Of the 18 included studies, 38.9% of the studies placed implants at the maxillary first molar, and 44.4% placed them at the alveolar ridge region anterior to the maxillary first molar. As for the induction method, the numbers of published studies on ligature methods, bacterial inoculation, and bacterial lipopolysaccharide inoculation were equally high among all selected studies. The total implant survival rate at the end was 160 out of 213 implants (75.11%). Eight studies with high pooled heterogeneity (I2 = 98, P < .01) in the meta-analysis reported an overall MBL (µ-CT) of 0.47 mm (95% CI = 0.14 to 0.81). A subgroup analysis estimated an MBL of 0.31 mm (95% CI = 0.12 to 0.50) for bacterial inoculation and 0.66 mm (95% CI = 0.07 to 1.26) for the ligature method. Histopathologic analysis revealed that peri-implantitis in rats was similar to peri-implantitis lesions in humans. Conclusions: Implant placement at the maxillary first molar with bacterial inoculation and the silk ligature method to build peri-implantitis rat models is reliable to use for research on peri-implantitis. [ABSTRACT FROM AUTHOR]

Purpose: To assess the pain, swelling, infection, and alteration in sensation following the flapless placement of zygomatic implants guided by dynamic navigation. Materials and Methods: A randomized controlled trial was conducted on 20 patients. In group 1, the placement of the zygomatic implants was carried out without reflecting a mucoperiosteal flap (flapless). In group 2, a mucoperiosteal flap was raised (flapped). Two zygomatic implants were placed in each patient (one on each side) under local anesthesia, guided by dynamic navigation. Postoperative evaluations included pain (using the visual analogue scale [VAS]), swelling (using standard measurements), maxillary sinus infection, and alteration of sensation (using mechanical stimuli, thermal threshold detection, and a two-point discrimination test). The assessments were carried out at 2 days, 1 week, and then 1, 2, and 3 months postoperatively. Results: In group 1, all implants except for one were successfully osseointegrated. Immediate postoperative pain and swelling were both significantly greater in group 2 (P < .01). No alteration in sensation was detected in any case in the two groups. There were a total of three cases of chronic sinusitis: one in group 1 and two in group 2. Conclusions: The flapless placement of zygomatic implants guided by dynamic navigation and under local anesthesia improves postoperative recovery. [ABSTRACT FROM AUTHOR]

Objective: Inflammatory pathogenesis is common to periodontitis and oral lichen planus. This study was conducted to assess and compare the periodontal status of patients with and without oral lichen planus. Method and materials: 108 patients comprising 54 with oral lichen planus and 54 age-matched systemically healthy participants without oral lichen planus were selected. Periodontal parameters, ie Plaque Index, Gingival Index, bleeding on probing, probing pocket depth, clinical attachment level, and periodontal phenotype were measured. Results: On comparing the test and control groups, statistically significant differences were observed in respect to Plaque Index (P = .00), Gingival Index (P = .00), and bleeding on probing (P = .00). A higher proportion of sites with deeper pockets was observed in the test group (P = .00). On comparison of various oral lichen planus subtypes, significant difference was observed in respect to Gingival Index (P = .00) and bleeding on probing (P = .00). A higher proportion of sites with deeper pockets (P = .01) and greater CAL (P = .00) was observed in the erosive/atrophic subgroup compared to the reticular group. However, the differences between the reticular (a less severe form of oral lichen planus) and control group in terms of Gingival Index (P = .94), Plaque Index (P = .05), bleeding on probing (P = .17), probing pocket depth (P = .56), and clinical attachment level (P = .23) were not statistically significant. Statistically significant differences were observed in terms of Gingival Index (P = .01) and bleeding on probing (P = .00) between thin and thick periodontal phenotypes in the oral lichen planus group. Statistically significant positive correlations in periodontal parameters with increased gingival involvement and severity were observed using Spearman rank correlation coefficient. Conclusion: Significantly greater periodontal inflammation in the test group means there is a risk of greater attachment loss in future. Thus, increased attention towards periodontal health in these patients might reduce the rate of disease progression. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the process of early oral osseointegration of titanium (Ti) implants in diabetic 129/Sv mice through microCT and histologic and immunohistochemical analysis. Materials and Methods: A group of 30 male 129/Sv mice was equally subdivided into two groups: (1) nondiabetic (ND), in which mice did not undergo systemic alterations and received a standard diet, and (2) diabetic (D), in which mice were provided a high-fat diet from the age of 6 weeks until the conclusion of the study and received two intraperitoneal (IP) injections of streptozotocin (STZ) at a concentration of 100 mg/Kg each. Each mouse underwent extraction of a maxillary first molar, and customized Ti screws (0.50 mm diameter, 1.5 mm length) were placed in the residual alveolar sockets of the palatal roots. At 7 and 21 days after implant placement, the animals were euthanized for maxilla and pancreas collection. Maxillae containing Ti implants were analyzed with microCT, histology, and immunohistochemistry for cells that were positive for F4/80, CD146, runt-related transcription factor 2 (Runx2), and proliferating cell nuclear antigen (PCNA). Pancreata were histologically analyzed. Quantitative data were statistically analyzed with a significance level at 5% (P < .05). Results: ND mice presented successful healing and osseointegration, with a significantly higher fraction of bone volume compared to D mice, both at the alveolar sockets (53.39 ± 5.93 and 46.08 ± 3.18, respectively) and at the implant sites (68.88 ± 7.07 and 44.40 ± 6.98, respectively) 21 days after implant placement. Histologic evaluation revealed that the ND mice showed a significant decrease in inflammatory infiltrate and a significant increase in newly formed bone matrix at 21 days, whereas peri-implant sites in the D mice were predominantly encapsulated by fibrous tissue and chronic inflammatory infiltrate. Immunohistochemical characterization revealed higher Runx2 osteoblast differentiation and higher cell proliferation activity in the ND mice at 7 days, while higher amounts of macrophages were present in D mice at 7 and 21 days. Interestingly, no differences were found in CD146-positive cells when comparing ND and D mice. Conclusions: This study evaluated the effects of immediate dental implant placement in 129/Sv diabetic mice by using specific healing markers to identify changes in cellular events involved in early oral osseointegration. This approach may serve as tool to evaluate new materials and surface coatings to improve osseointegration in diabetic patients. [ABSTRACT FROM AUTHOR]

Background: Children with inflammatory bowel disease (IBD) experience extraintestinal side effects including altered body composition, impaired muscle strength, and aerobic capacity. Exercise training may remedy these issues. Purpose: To assess the feasibility, safety, participant satisfaction, and efficacy of a training program for youth with IBD. Methods: Children with IBD completed 16 weeks of training (2 supervised + 1 home sessions per week). Feasibility was assessed by tracking recruitment, adherence, and compliance rates. Safety was assessed by tracking symptoms and adverse events. Posttraining interviews gauged satisfaction. Circulating inflammatory markers, body composition, muscle strength, aerobic fitness, and habitual physical activity were measured at baseline, midtraining (8 wk), and posttraining. Results: Eleven youth were recruited and 10 completed the study. Participants adhered to 28 (1) of 32 prescribed supervised sessions and 8 (4) of 16 prescribed home sessions. There were no adverse events, and overall feedback on training was positive. Posttraining, we observed an increase in lean mass (+2.4 [1.1] kg), bone density (+0.0124 [0.015] g·cm−2), aerobic fitness (+2.8 [5.7] mL·kg LM−1· min−1), and vigorous physical activity levels (+13.09 [8.95] min·h−1) but no change in inflammation or muscle strength. Conclusion: Supervised exercise training is feasible, safe, and effective for youth with IBD and should be encouraged. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of supragingival scaling on the clinical outcomes of subgingival instrumentation completed after 1 week. Method and materials: In 27 patients with Stage II and Stage III periodontitis, pairs of contralateral quadrants were randomly assigned into test group 1 (single sitting scaling and root planing) and test group 2 (supragingival scaling followed by subgingival instrumentation after lweek). Periodontal parameters were recorded at baseline, 2, 4, and 6months; Gingival crevicular fluid vascular endothelial growth factor (VEGF) estimation was done at baseline in both groups and 7 days after supragingival scaling in test group 2. Results: At 6 months, significantly better improvement in test group 1 at sites with periodontal probing depth (PPD)>5mm; (APPD = 2.32 mm vs 1.41 mm, P= .001; Aclinical attachmen level [CAL] = 2.34 mm vs 1.39 mm, P=.001) was observed. Supragingival scaling resulted in significant reduction in gingival crevicular fluid VEGF (42.46 to 27.88 pg/site) after lweek. Regression analysis explained 14% variance in VEGF to baseline PPD at sites with PPD>4 mm; and 21% variance in CAL improvement to VEGF at sites with PPD>5mm. The percentage of sites with PPD = 5 to 8 mm reachingthe clinical endpoint was 52% and 40%fortest group 1 and test group 2, respectively. Better results were noticed in bleeding on pocket probing-positive sites in both groups. Conclusion: The sites with PPD > 5 mm where supragingival scaling was followed by subgingival instrumentation after 1 weekresulted in less favourable treatment outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To compare bone substitutes composed of glycated collagen with synthetic micro-sized (1 to 10 µm) hydroxyapatite (OB) vs non-cross-linked collagen matrix with large-particle (250 to 1,000 µm) bovine-derived hydroxyapatite (BOC). Materials and Methods: The P1 to P4 premolars were bilaterally extracted from the mandibles of 19 Beagle dogs. After 21 days, osteotomies were created in each dog that received OB or BOC and were covered with a collagen membrane or were left untreated. The animals were randomly divided into three groups based on sacrifice time (4, 12, or 24 weeks). The right and left hemimandibles were trimmed to facilitate imaging and histology, and all tissues were placed in 10% neutral-buffered formalin. Microcomputed tomography (MicroCT 40 Scanner, Scanco) was used to analyze bone sections. Bone volume, residual material volume, and bone mineral density were determined for each treatment site (OB and BOC) based on a volume of interest that encompassed the original defect. Additionally, blinded histopathologic assessment (based on the ISO 10993-6 scoring system) and histomorphometry were performed on sections ground to < 100 µm thick and stained with Stevenel's blue. Results: No clinical side effects were noted. No statistical differences were observed for OB vs BOC regarding the mineral volume percentage. Compared to OB, BOC had significantly higher mean mineralization densities at 12 weeks (P < .01), but this difference did not extend to 24 weeks. For residual grafting material, bone maturation, alveolar ridge restoration, and inflammatory response, OB showed a residual amount of bone graft and no statistical differences compared to BOC. Conclusion: Both OB and BOC represent valid treatment options for critically sized bone defects. Both bone fillers outperformed the sham-operated, ungrafted (empty) control, demonstrating statistically improved bone growth and ridge restoration. [ABSTRACT FROM AUTHOR]

Introduction: The resolution of the skin's inflammatory response is only possible if its barrier function is restored. TRPV1 channel activation plays an important role during inflammation but the effect of this activation on the skin barrier under inflammatory conditions has not been clarified. We hypothesize that it could potentially aid the keratinocyte barrier by reducing inflammatory cytokine release and promoting tight junction development. Methods: To explore the role of TRPV1 activation in inflammation, we designed and optimized an in vitro model of keratinocytes with basal epidermal layer characteristics using HaCaT cells and TNFα to induce inflammation. Results: TNFα increased the gene expression of tight junction protein claudin 1 (CLDN1) by at least 2.60 ± 0.16-fold, in a concentration-dependent manner, over a 48 h period. The administration of a capsaicin pre-treatment reduced the CLDN1 expression to 1.51 ± 0.16-fold during the first 6 h after TNFα induction, whereas IL-8 cytokine release was reduced 0.64 ± 0.17-fold. After 48 h, CLDN1 protein levels increased by a factor of 6.57 ± 1.39 compared to cells only treated with TNFα. Discussion: These results suggest that activation of TRPV1 by capsaicin can potentiate the increase in CLDN1 expression and CLDN1 protein synthesis induced by TNFα in cultured keratinocytes, while reducing the release of IL-8. [ABSTRACT FROM AUTHOR]

Background: Skin photoaging induced by ultraviolet A (UVA) and ultraviolet B (UVB) radiation manifests as skin roughness, desquamation, pigmentation, and wrinkle formation. Current treatments, such as sunscreen, hormones, and antioxidants, have limitations and side effects. Traditional Chinese Medicine Hibisci Mutabilis Folium (HMF), or Mu-Fu-Rong-Ye in Chinese name, refers to the dried leaves of the plant Hibiscus mutabilis L., which belongs to the Malvaceae family. It has been used traditionally to treat acute mastitis, parotitis, neurodermatitis, burns. The reported activities of HMF include antiinflammatory and anti-oxidant effects. However, the therapeutic potential of HMF in preventing and treating UV-induced skin photoaging remains unexplored. Objective: This study aimed to investigate the protective effects of HMF extract (EHMF) against UV-induced skin photoaging and the underlying mechanisms of action, by using network pharmacology and experimental verification. Methods: Network pharmacology was employed to identify the effective chemical components of EHMF. Potential targets were identified via PPI network analysis. Representative compounds were characterized using UPLCMS/MS. In vitro validation involved assessing HaCaT cell viability, observing live/dead cell staining through fluorescence microscopy, and measuring inflammatory factors using ELISA. For in vivo validation, a UV-induced skin photoaging mice model was treated transdermally with EHMF or Methotrexate daily for 7 days. Dermatitis severity, skin morphology, and collagen fiber pathology were evaluated. Inflammatory cytokine and protein expression in dorsal skin lesions was confirmed using Elisa Kits, Western blot and immunohistochemistry. Results: A total of 22 active ingredients of EHMF were identified. GO enrichment and KEGG pathway analyses revealed a focus on inflammatory signaling pathways. In vitro experiments showed that EHMF significantly reduced UV-induced inflammatory factors in HaCaT cells and improved cell survival rates. In vivo, EHMF alleviated back skin lesions in UV-exposed mice, reducing epidermal and dermal thickening and pathological inflammatory cell infiltration. It also decreased abnormal MMP-9 expression and collagen fiber proliferation, along with levels of inflammatory factors like TNF-α, IL-6, IL-17, and EGFR. Western blot and immunohistochemistry results indicated that the over-activation of the AKTSTAT3 signaling pathway was inhibited. Conclusion: EHMF effectively reduced UV-induced skin damage, inflammation, and wrinkles, providing strong support for its clinical application as a dermatological agent. [ABSTRACT FROM AUTHOR]

Background: Microecological equilibrium is essential for human health. Previous research has demonstrated that Streptococcus strain A, the main bacterial group in the respiratory tract, can suppress harmful microbes and protect the body. In this study, Streptococcus strain D19T was isolated from the oral and pharyngeal cavities of healthy children. Its antibacterial mechanism against Acinetobacter baumannii was examined, as well as its potential to prevent inflammatory damage to cells. We evaluated the effect of the fermentation conditions of D19T on inhibition of Acinetobacter baumannii growth; Isolation and purification of antibacterial active components of strain D19T and molecular mechanism of inhibition of Acinetobacter baumannii; Molecular mechanism of D19T antibacterial protein reversing cellular inflammatory injury induced by Acinetobacter baumannii. Results: The supernatant of fermentation broth of Streptococcus D19T was the active component against Acinetobacter baumannii, but the bacteria had no antibacterial activity. The supernatant of D19T fermentation broth was precipitated by (NH4)2SO4 solution, and the protein was the active antibacterial component. After gel filtration chromatography and anion gel filtration chromatography, the molecular weight of antibacterial protein was 53kD. D19T antibacterial protein can improve cell membrane permeability, limit extracellular soluble protein release, inhibit Acinetobacter baumannii biofilm formation, and prevent Acinetobacter baumannii adhesion. Acinetobacter baumannii induces inflammatory damage to respiratory cells via ferroptosis, and the D19T antibacterial protein can counteract this damage, protecting the respiratory tract. Conclusion: Streptococcus strain D19T, as a potential probiotic, inhibits the growth of Acinetobacter baumannii and the inflammatory damage of respiratory cells, playing a protective role in human respiratory health. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii (T. gondii), an obligate intracellular protozoan parasite, is increasingly recognized for its role in various human diseases, including periodontal diseases. Periodontal diseases comprise a wide range of inflammatory conditions that not only affect the supporting structures of the teeth and oral health but also contribute to systemic diseases. The parasite's ability to modulate the host's immune response and induce chronic inflammation within the periodontium is a key factor in periodontal tissue damage. Through its virulence factors, T. gondii disrupts the balance of inflammatory cytokines, leading to dysregulated immune responses, and exacerbates oxidative stress in periodontal tissues. And T. gondii invasion could affect specific proteins in host cells including HSP70, BAGs, MICs, ROPs, SAGs, and GRAs leading to periodontal tissue damage. The indirect role of the host immune response to T. gondii via natural killer cells, monocytes, macrophages, neutrophils, dendritic cells, T cells, and B cells also contributes to periodontal diseases. Understanding these complex interactions of T. gondii with host cells could unravel disease mechanisms and therapeutic targets for periodontal diseases. This review delves into the pathogenic mechanisms of T. gondii in periodontal diseases, offering a detailed exploration of both direct and indirect pathways of its impact on periodontal health. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus, which causes great health damage and economic burden to patients. The pathogenesis of DFU is not fully understood. We screened wound healing-related genes using bioinformatics analysis, and full-thickness skin injury mice model and cellular assays were used to explore the role of target genes in diabetic wound healing. SFRP2 was identified as a wound healing-related gene, and the expression of SFRP2 is associated with immune cell infiltration in DFU. In vivo study showed that suppression of SFRP2 delayed the wound healing process of diabetic mice, impeded angiogenesis and matrix remodeling, but did not affect wound healing process of control mice. In addition, suppression of SFRP2 increased macrophage infiltration and impeded the transition of macrophages functional phenotypes during diabetic wound healing, and affected the transcriptome signatures-related to inflammatory response and energy metabolism at the early stage of wound healing. Extracellular flux analysis (EFA) showed that suppression of SFRP2 decreased mitochondrial energy metabolism and increased glycolysis in injury-related macrophages, but impeded both glycolysis and mitochondrial energy metabolism in inflammatory macrophages. In addition, suppression of SFRP2 inhibited wnt signaling-related genes in macrophages. Treatment of AAV-SFRP2 augmented wound healing in diabetic mice and demonstrated the therapeutic potential of SFRP2. In conclusions, SFRP2 may function as a wound healing-related gene in DFU by modulating functional phenotype transition of macrophages and the balance between mitochondrial energy metabolism and glycolysis. [ABSTRACT FROM AUTHOR]

Introduction: Hypersensitivity pneumonitis (HP) is an extrinsic allergic alveolitis characterized by inflammation of the interstitium, bronchioles, and alveoli of the lung that leads to granuloma formation. We previously found that activation of protein kinase D1 (PKD1) in the lungs following exposures to Saccharopolyspora rectivirgula contributes to the acute pulmonary inflammation, IL-17A expression in the lungs, and development of HP. In the present study, we investigated whether PKD1 in myeloid-lineage cells affects the pathogenic course of the S. rectivirgula-induced HP. Methods: Mice were exposed intranasally to S. rectivirgula once or 3 times/week for 3 weeks. The protein and mRNA expression levels of cytokines/chemokines were detected by enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. Flow cytometry was used to detect the different types of immune cells and the levels of surface proteins. Lung tissue sections were stained with hematoxylin and eosin, digital images were captured, and immune cells influx into the interstitial lung tissue were detected. Results: Compared to control PKD1-sufficient mice, mice with PKD1 deficiency in myeloid-lineage cells (PKD1mKO) showed significantly suppressed expression of TNFα, IFNγ, IL-6, CCL2, CCL3, CCL4, CXCL1, CXCL2, and CXCL10 and neutrophilic alveolitis after single intranasal exposure to S. rectivirgula. Substantially reduced levels of alveolitis and granuloma formation were observed in the PKD1mKO mice repeatedly exposed to S. rectivirgula for 3 weeks. In addition, expression levels of the Th1/Th17 polarizing cytokines and chemokines such as IFNγ, IL-17A, CXCL9, CXCL10, CXCL11, and CCL20 in lungs were significantly reduced in the PKD1mKO mice repeatedly exposed to S. rectivirgula. Moreover, accumulation of CXCR3+CCR6+ nonconventional Th1 in the lungs were significantly reduced in PKD1mKO mice repeatedly exposed to S. rectivirgula. Discussion: Our results demonstrate that PKD1 in myeloid-lineage cells plays an essential role in the development and progress of HP caused by repeated exposure to S. rectivirgula by contributing Th1/Th17 polarizing proinflammatory responses, alveolitis, and accumulation of pathogenic nonconventional Th1 cells in the lungs. [ABSTRACT FROM AUTHOR]

Introduction: Immune checkpoint blockade (ICB) immunotherapy has revolutionized cancer treatment, demonstrating exceptional clinical responses in a wide range of cancers. Despite the success, a significant proportion of patients still fail to respond, highlighting the existence of unappreciated mechanisms of immunotherapy resistance. Delineating such mechanisms is paramount to minimize immunotherapy failures and optimize the clinical benefit. Methods: In this study, we treated tumour-bearing mice with PD-L1 blockage antibody (aPD-L1) immunotherapy, to investigate its effects on cancer-induced emergency myelopoiesis, focusing on bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs). We examined the impact of aPD-L1 treatment on HSPC quiescence, proliferation, transcriptomic profile, and functionality. Results: Herein, we reveal that aPD-L1 in tumour-bearing mice targets the HSPCs in the BM, mediating their exit from quiescence and promoting their proliferation. Notably, disruption of the PDL1/PD1 axis induces transcriptomic reprogramming in HSPCs, observed in both individuals with Hodgkin lymphoma (HL) and tumour-bearing mice, shifting towards an inflammatory state. Furthermore, HSPCs from aPDL1-treated mice demonstrated resistance to cancer-induced emergency myelopoiesis, evidenced by a lower generation of MDSCs compared to control-treated mice. Discussion: Our findings shed light on unrecognized mechanisms of action of ICB immunotherapy in cancer, which involves targeting of BM-driven HSPCs and reprogramming of cancer-induced emergency myelopoiesis. [ABSTRACT FROM AUTHOR]

ApoB insertion/deletion (ins/del) genetic variant (rs11279109) is thought to be related to cardio-metabolic markers and obesity. This association has the potential to be modified by dietary patterns. Since the majority of studies concerned the role of dietary acid load (DAL) or ApoB in type 2 diabetes mellitus (T2DM) and its complications independently, and due to the insufficient data regarding the possible interactions between ApoB genetic variants and DAL on anthropometric and metabolic markers, we aimed to study the interaction between this genetic variant and dietary acid load (DAL) on cardio-metabolic markers, along with leptin among Iranian individuals with T2DM. 700 T2DM patients were randomly recruited. A validated semi-quantitative food frequency questionnaire was used for DAL calculation including potential renal acid load (PRAL) and net-endogenous acid production (NEAP). The polymerase chain reaction was used for genotyping the ApoB ins/del (rs11279109). The general linear model was applied to find the interactions in the crude and adjusted models. Patients with del/del genotype (rs11279109) with high PRAL intake have lower low-density lipoprotein cholesterol (LDL-C) (Pinteraction = 0.004), LDL/HDL ratio (Pinteraction = 0.02), total cholesterol (TC) (Pinteraction = 0.04), triglyceride (TG) (Pinteraction = 0.04), leptin (Pinteraction = 0.04) and interleukin-18 (IL-18) (Pinteraction = 0.04). Moreover, the interaction of gene and DAL in the PRAL method on TG concentration (P = 0.04), waist circumference (WC) (P = 0.04), and LDL/HDL ratio (P = 0.04) were significant. Eventually, a positive relationship was observed between the presence of the del/del genotype (rs11279109) and higher levels of TG, TC, LDL-C, IL-18, and LDL/HDL, in individuals with lower adherence to DAL, after adjusting for various covariates. Further studies are needed to investigate and confirm these findings. [ABSTRACT FROM AUTHOR]

The spinal muscular atrophy (SMA) phenotype strongly correlates with the SMN2 gene copy number. However, the severity and progression of the disease vary widely even among affected individuals with identical copy numbers. This study aimed to investigate the impact of genetic variability in oxidative stress, inflammatory, and neurodevelopmental pathways on SMA susceptibility and clinical progression. Genotyping for 31 genetic variants across 20 genes was conducted in 54 SMA patients and 163 healthy controls. Our results revealed associations between specific polymorphisms and SMA susceptibility, disease type, age at symptom onset, and motor and respiratory function. Notably, the TNF rs1800629 and BDNF rs6265 polymorphisms demonstrated a protective effect against SMA susceptibility, whereas the IL6 rs1800795 was associated with an increased risk. The polymorphisms CARD8 rs2043211 and BDNF rs6265 were associated with SMA type, while SOD2 rs4880, CAT rs1001179, and MIR146A rs2910164 were associated with age at onset of symptoms after adjustment for clinical parameters. In addition, GPX1 rs1050450 and HMOX1 rs2071747 were associated with motor function scores and lung function scores, while MIR146A rs2910164, NOTCH rs367398 SNPs, and GSTM1 deletion were associated with motor and upper limb function scores, and BDNF rs6265 was associated with lung function scores after adjustment. These findings emphasize the potential of genetic variability in oxidative stress, inflammatory processes, and neurodevelopmental pathways to elucidate the complex course of SMA. Further exploration of these pathways offers a promising avenue for developing personalized therapeutic strategies for SMA patients. [ABSTRACT FROM AUTHOR]

Olfactory loss accompanies at least 139 neurological, somatic, and congenital/hereditary conditions. This observation leads to the question of whether these associations are correlations or whether they are ever causal. Temporal precedence and prospective predictive power suggest that olfactory loss is causally implicated in many medical conditions. The causal relationship between olfaction with memory dysfunction deserves particular attention because this sensory system has the only direct projection to memory centers. Mechanisms that may underlie the connections between medical conditions and olfactory loss include inflammation as well as neuroanatomical and environmental factors, and all 139 of the medical conditions listed here are also associated with inflammation. Olfactory enrichment shows efficacy for both prevention and treatment, potentially mediated by decreasing inflammation. [ABSTRACT FROM AUTHOR]

Postoperative abdominal adhesion is one of the most common complications after abdominal surgery. The Toll-like receptor 4 (TLR4) signaling pathway is one of the most common inflammation-related pathways, and it has been demonstrated that TLR4 is highly expressed in adhesive tissues; however, the function of TLR4 in adhesion formation has not yet been studied. In the present study, the expression of TLR4 was first detected by immunohistochemical (IHC) and double-immunofluorescence staining in 40 mice, which were randomly divided into four groups, and sacrificed at 1, 3, 5 and 7 days after surgery. Subsequently, another 40 mice were randomly divided into five groups; with the exception of the sham group, the other groups were modeled and treated with saline that contained DMSO, sodium hyaluronate (HA), TAK-242 or TAK-242 + HA (applied to damaged peritoneal wounds). A total of 7 days after surgery, the mice were sacrificed and specimens were collected. Inflammation was detected by hematoxylin and eosin staining, and ELISA of transforming growth factor- β1 (TGF-β1) and interleukin-6 (IL-6); collagen deposition was examined by Masson staining and IHC staining of α-SMA; and reactive oxygen species (ROS) were detected by ROS staining and malondialdehyde (MDA) assay. The results revealed that TLR4 was highly expressed in the adhesive tissues at 3, 5 and 7 days after surgery. In addition, TAK-242 + HA treatment could reduce abdominal adhesion formation, exhibiting lower Nair's score and inflammation scores, lower TGF-β1 and IL-6 levels, and lower collagen thickness and α-SMA levels compared with those in the control group. In addition, the TAK-242 + HA group had lower levels of ROS and MDA compared with those in the control group. The present study revealed that TLR4 was highly expressed in the process of adhesion formation and its inhibitor, TAK-242, combined with HA, could reduce adhesion formation by reducing inflammation and ROS, and alleviating collagen deposition. [ABSTRACT FROM AUTHOR]

Objectives: The study aimed to investigate the interaction of intraoperative stress hyperglycemia with monocyte functions and their impact on major adverse events (MAEs) in acute aortic dissection (AAD) patients who underwent open repair surgery. Methods: A total of 321 adults who underwent open surgery for AAD at two tertiary medical centers in China were enrolled in the study. The primary endpoint was defined as the incidence and characteristics of perioperative stress hyperglycemia. The secondary endpoints included the incidence of postoperative MAEs, postoperative monocyte counts and inflammatory cytokine expression. Multi-logistic, linear regression and receiver operating characteristic (ROC) curve analyses were used to establish relationships between intraoperative time-weighted average glucose (TWAG), day-one postoperative monocyte counts, serum inflammatory cytokines and postoperative outcomes. In addition, in vitro experiments were conducted to evaluate changes in the inflammatory features of monocytes under high glucose conditions. Results: Intraoperative hyperglycemia, as indicated by a TWAG level over 142 mg/dL, was associated with elevated postoperative monocyte counts and inflammatory cytokines, which correlated with extended intensive care unit (ICU) stays and worsened outcomes. In vitro, high glucose treatment induced mitochondrial impairment in monocytes, increased the release of inflammatory cytokines and the proportion of classical monocytes from AAD patients. Conclusions: Intraoperative stress hyperglycemia, in combination with day-one postoperative monocyte counts, were clinically significant for predicting adverse outcomes in AAD patients undergoing open repair surgery. Elevated glucose concentrations shaped the inflammatory features of monocytes in AAD by impairing mitochondrial functions. High glucose-driven mitochondrial functional impairment mediates a more pronounced monocytic inflammatory state in Stanford type-A AAD. [ABSTRACT FROM AUTHOR]

Background: The exact mechanisms underlying depression are not well understood. Chronic, low-grade inflammation is believed to play an important role in its development. The present study investigates the potential association between depressive symptoms and the neutrophil-to-lymphocyte ratio (NLR). Methods: Seven data cycles of the National Health and Nutrition Examination Survey were extracted. Multivariable logistic regression and a generalized additive model were employed to determine the association. Results: Thirty thousand eight hundred ninety-six subjects were analyzed. The results indicated that anhedonia and fatigue were significantly associated with NLR. Additionally, the generalized additive model results indicated a non-linear relationship between anhedonia, sleep disturbance and NLR. Subgroup analyses demonstrated that the correlation between anhedonia and NLR was significant in the above-60-year-old group (OR: 1.63, 95% CI: 1.14–2.33) and the male group (OR: 1.50, 95% CI: 1.07–2.10). Sleep disturbance was associated with NLR in the female group (OR: 1.36, 95% CI: 1.04–1.77). Fatigue was associated with NLR (OR: 1.30, 95% CI: 1.02–1.67) in the female group, as was the case in the non-Hispanic White group (OR: 1.32, 95% CI: 1.02–1.70). Conclusions: There were associations between NLR and specific symptoms, and these associations varied across demographic subgroups. There was a non-linear association between anhedonia, sleep disturbance and NLR. These findings could potentially contribute to the advancement of precision medicine within the field of mental health. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) imposes a significant health burden on patients globally. Chronic low-grade inflammation is pivotal in the onset and progression of this condition. However, the role of the novel inflammatory marker, red cell distribution width to albumin ratio (RAR), in the development of MetS remains unclear. Methods: This population-based cross-sectional study utilized data from the 2011–2020 National Health and Nutrition Examination Survey (NHANES). Participants included individuals over 18 years old with complete data on serum albumin concentration, red cell distribution, and MetS and its components. MetS was defined using the criteria established by the National Cholesterol Education Program Adult Treatment Panel III. The calculation formula for RAR is: RAR = Red cell distribution width (%)/serum albumin (g/dL). Study participants were stratified into four quartiles based on RAR levels. Logistic regression analysis and subgroup analysis were employed to explore the independent interaction between RAR and MetS, as well as investigate the relationship between RAR levels and the specific components of MetS. Finally, the receiver operating characteristic (ROC) curve was used to assess the predictive efficacy of RAR for MetS. Results: A total of 4899 participants were included in this study, comprising 2450 males and 2449 females; 1715 individuals (35.01%) were diagnosed with MetS. As the quartile of RAR increased, the proportion of individuals with MetS also increased. Spearman correlation analysis indicated a positive correlation between RAR and the insulin resistance index HOMA-IR. Logistic regression analysis, adjusting for multiple confounding factors, showed that each standard deviation increase in RAR was associated with a significant 1.665-fold increase (95% CI, 1.404–1.975; P < 0.001) in the odds of MetS prevalence. In logistic regression analysis stratified by quartiles of RAR, the risks of MetS in Q1-Q4 were 1.372 (95% CI, 1.105–1.704; P = 0.004), 1.783 (95% CI, 1.434–2.216; P < 0.001), and 2.173 (95% CI, 1.729–2.732; P < 0.001), respectively. Subgroup analyses and interaction tests demonstrated that gender, age, race, education, smoking status, and physical activity modified the positive association between RAR and MetS (p for interaction < 0.05). Additionally, analysis of the area under the receiver operating characteristic (ROC) curve showed that the optimal cutoff value for predicting MetS using RAR was 3.1348 (sensitivity: 59.9%; specificity: 60.6%; and AUC: 0.628). Conclusions: Increasing RAR levels are associated with a higher risk of MetS. Therefore, greater attention should be given to patients with high RAR levels for improved prevention and treatment of MetS. [ABSTRACT FROM AUTHOR]

Inflammation is a vital immune defense mechanism regulated by Toll‐like receptors (TLRs) and the nuclear factor‐kappa B (NF‐κB) pathway. TANK‐binding kinase 1 (TBK1) is central to immunity and inflammation and influences antiviral responses and cellular processes. However, the precise role of TBK1 in modulating the NF‐κB pathway through interactions with other proteins, such as spleen tyrosine kinase (Syk), remains poorly understood. As dysregulation of TBK1 and NF‐κB can lead to a variety of diseases, they are important therapeutic targets. In this work, inflammatory processes involving the TBK1‐Syk‐NF‐κB pathway were elucidated using lipopolysaccharide (LPS)‐induced macrophages; human embryonic kidney 293 (HEK293) cells overexpressing MyD88, TBK1, and Syk proteins and their mutants; and real‐time polymerase chain reaction (PCR), immunoblotting analyses, and kinase assays. TBK1 was activated in LPS‐, poly I:C‐, and Pam3CSK‐stimulated macrophages. Transcript levels of TNF, NOS2, and IL1B were increased in cells overexpressing TBK1 but not in cells overexpressing TBK1 K38A. The transcription of TNF, NOS2, and IL1B and NF‐κB luciferase activity were inhibited by silencing TBK1 in LPS‐stimulated RAW264.7 cells and MyD88‐transfected HEK293 cells. Syk was the key mediator of the TBK1‐dependent NF‐κB pathway and bound directly to the coiled coil domain of TBK1, which was necessary to activate Syk and the Syk‐p85 pathway. This research advances the understanding of the role of TBK1 in NF‐κB signaling, emphasizing Syk as a key mediator. The interaction between TBK1 and Syk has potential for precise immune modulation that can be applied to treat immune‐related disorders. [ABSTRACT FROM AUTHOR]

Background: In Parkinson's patients, intestinal dysbiosis can occur years before clinical diagnosis, implicating the gut and its microbiota in the disease. Recent evidence suggests the gut microbiota may trigger body-first Parkinson Disease (PD), yet the underlying mechanisms remain unclear. This study aims to elucidate how a dysbiotic microbiome through intestinal immune alterations triggers PD-related neurodegeneration. Methods: To determine the impact of gut dysbiosis on the development and progression of PD pathology, wild-type male C57BL/6 mice were transplanted with fecal material from PD patients and age-matched healthy donors to challenge the gut-immune-brain axis. Results: This study demonstrates that patient-derived intestinal microbiota caused midbrain tyrosine hydroxylase positive (TH +) cell loss and motor dysfunction. Ileum-associated microbiota remodeling correlates with a decrease in Th17 homeostatic cells. This event led to an increase in gut inflammation and intestinal barrier disruption. In this regard, we found a decrease in CD4 + cells and an increase in pro-inflammatory cytokines in the blood of PD transplanted mice that could contribute to an increase in the permeabilization of the blood–brain-barrier, observed by an increase in mesencephalic Ig-G-positive microvascular leaks and by an increase of mesencephalic IL-17 levels, compatible with systemic inflammation. Furthermore, alpha-synuclein aggregates can spread caudo-rostrally, causing fragmentation of neuronal mitochondria. This mitochondrial damage subsequently activates innate immune responses in neurons and triggers microglial activation. Conclusions: We propose that the dysbiotic gut microbiome (dysbiome) in PD can disrupt a healthy microbiome and Th17 homeostatic immunity in the ileum mucosa, leading to a cascade effect that propagates to the brain, ultimately contributing to PD pathophysiology. Our landmark study has successfully identified new peripheral biomarkers that could be used to develop highly effective strategies to prevent the progression of PD into the brain. [ABSTRACT FROM AUTHOR]

Some drugs or chemicals exhibit different safety profiles in newborns/young children compared to adults. Polyhexamethyleneguanidine phosphate (PHMG-P) has been implicated in the humidifier disinfectant tragedy in 2011. There are limited reports on the toxicity of PHMG-P in neonatal animals. This study aimed to assess the toxicity of PHMG-P in neonates and to compare toxicity between young and adult mice. Mice aged 7–10 days and 8 weeks were anesthetized with isoflurane and then intranasally instilled with 0.9 mg/kg and 1.5 mg/kg PHMG-P once weekly for 4 weeks. The control group was given a corresponding volume of saline intranasally. Approximately 20 h after the 4th instillation, all mice (juveniles aged 28‒31 days and adults aged 11 weeks) were euthanized. Assessments included body weights, organ weights, cytokine production, and histopathological examinations. Both juvenile and adult mice exhibited significant pulmonary toxicity. There were no significant changes in body weight in either male or female juveniles, whereas adult mice experienced 5.0‒22.2% weight loss. However, lung weights increased in both age groups, accompanied by rises in cytokines and chemokines. Histopathological analyses revealed significant lung changes in both juvenile and adult mice, including immune cell infiltration, foamy macrophage, and granulomatous inflammation. PHMG-P is known to cause inflammation and fibrotic changes in rodents and humans that persist even during long recovery periods. Further research is required to explore the long-term health effects of PHMG-P following repeated early-life exposure. [ABSTRACT FROM AUTHOR]

This study aimed to explore the potential association between Endothelin type A receptor (EDNRA) genetic polymorphisms and susceptibility to large artery atherosclerotic stroke (LAA), as well as the involvement of inflammation mechanisms. We recruited Han Chinese patients with LAA and age- and sex-matched controls. The distribution of alleles and genotypes for 16 single nucleotide polymorphisms (SNPs) in EDNRA was analyzed using dominant, recessive, and co-dominant genetic models between cases and controls. We quantified the mRNA and protein levels of EDNRA and NLRP3 genes, and concentrations of inflammatory factors (TNFα, IL-1β, IL-6, IL-8, IL-10, IL-18, and CCL18) in peripheral blood samples randomly selected from cases and controls. We also investigated the relationship between these SNPs, gene expression patterns and inflammatory factor levels. A total of 428 LAA cases and 434 controls were enrolled in this study. The results showed that rs5343 TT genotype of EDNRA was significantly associated with an increased risk of LAA (OR = 3.243, 95%CI = 1.608–6.542, P = 0.001). It also demonstrated a significant upregulation level of NLRP3 as well as higher concentrations of IL-10, IL-18, and CCL-18 in cases compared to controls. Besides, we discovered that the EDNRA polymorphisms were linked to NLRP3, IL-6, IL-10, and IL-18 levels in cases. There existed a positive correlation between EDNRA transcription levels and both NLRP3 transcript levels (r = 0.437, p < 0.001) and IL-18 concentrations (r = 0.212, p < 0.001). EDNRA is linked to susceptibility of LAA. This association may be attributed to the NLRP3-mediated inflammatory pathway. [ABSTRACT FROM AUTHOR]

Introduction: Atherosclerosis (AS) is considered the underlying cause of many diseases, particularly cardiovascular and cerebrovascular diseases. Inulin, a type of fructan, has shown potential in improving atherosclerosis, although there are conflicting findings. It is hypothesized that the polymerization degree of inulin may largely influence its therapeutic effectiveness. Therefore, this study aimed to investigate the effects and mechanisms of short-chain and long-chain inulin in AS. Methods: ApoE−/− mice fed a high fat diet (HFD) were used to establish an atherosclerosis model. These mice received daily oral administration of either short-chain or long-chain inulin for 12 weeks. Plasma lipid metabolism-related indices were measured using biochemical analysis, and plasma immunological indices were analyzed via ELISA. The aorta, aortic root regions, liver tissue, adipose tissue, and colon tissue were examined through various staining techniques, including ORO staining, hematoxylin and eosin staining, Alcian blue staining, and immunofluorescent or immunohistochemical assays. Microbiome analysis was conducted in the cecal content. Results: The results indicated that both short-chain and long-chain inulin substantially reduced the formation of atherosclerotic plaques. Inulin also improved plasma lipid concentrations and hepatic lipid metabolism, and partially alleviated both localized (atherosclerotic lesions) and systemic inflammation. Short-chain inulin was more effective than long-chain inulin in reducing atherosclerotic plaques formation, enhancing lipid metabolism and reducing inflammation. Additionally, both types of inulin showed similar effectiveness in enhancing intestinal epithelial barrier integrity, gut microbiota composition and functionality. Conclusion: These findings suggest that inulin has a protective role against atherosclerosis by enhancing lipid metabolism, reducing inflammation, and improving intestinal barrier and gut microbiota. As a dietary intervention, shortchain inulin is more effective than long-chain inulin, offering clinical implications for using inulin as a therapeutic agent for atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Inflammation is characterized by a metabolic switch promoting glycolysis and lactate production. Hexokinases (HK) catalyze the first reaction of glycolysis and inhibition of epithelial HK2 protected from colitis in mice. HK2 expression has been described as elevated in patients with intestinal inflammation; however, there is conflicting data from few cohorts especially with severely inflamed individuals; thus, systematic studies linking disease activity with HK2 levels are needed. Methods: We examined the relationship between HK2 expression and inflammation severity using bulk transcriptome data derived from the mucosa of thoroughly phenotyped inflammatory bowel disease (IBD) patients of two independent cohorts including both subtypes Crohn's disease (CD) and ulcerative colitis (UC). Publicly available single-cell RNA sequencing data were analyzed, and immunofluorescence staining on colonic biopsies of unrelated patients with intestinal inflammation was performed to confirm the RNA-based findings on cellular and protein level. Results: HK2 expression gradually increased from mild to intermediate inflammation, yet strongly declined at high inflammation scores. Expression of epithelial marker genes also declined at high inflammation scores, whereas that of candidate immune marker genes increased, indicating a cellular remodeling of the mucosa during inflammation with an infiltration of HK2-negative immune cells and a loss of terminal differentiated epithelial cells in the apical epithelium—the main site of HK2 expression. Normalizing for the enterocyte loss clearly identified epithelial HK2 expression as gradually increasing with disease activity and remaining elevated at high inflammation scores. HK2 protein expression was mostly restricted to brush border enterocytes, and these cells along with HK2 levels vanished with increasing disease severity. Conclusions: Our findings clearly define dysregulated epithelial HK2 expression as an indicator of disease activity in intestinal inflammation and suggest targeted HK2-inhibition as a potential therapeutic avenue. [ABSTRACT FROM AUTHOR]

CXCL13 is a chemokine that plays an important role in the regulation and development of secondary lymphoid organs. CXCL13 is also involved in the regulation of pathological processes, particularly inflammatory responses, of many diseases. The function of CXCL13 varies depending on the condition of the host. In a healthy condition, CXCL13 is mainly secreted by mouse stromal cells or human follicular helper T cells, whereas in diseases conditions, they are produced by human peripheral helper T cells and macrophages in non-lymphoid tissues; this is termed ectopic expression of CXCL13. Ectopic CXCL13 expression is involved in the pathogenesis of various immune-mediated inflammatory diseases as it regulates the migration of B lymphocytes, T lymphocytes, and other immune cells in inflammatory sites as well as influences the expression of inflammatory factors. Additionally, ectopic expression of CXCL13 plays a key role in ectopic lymphoid organ formation. In this review, we focused on the sources of CXCL13 in different conditions and its regulatory mechanisms in immune-mediated inflammatory diseases, providing novel ideas for further research on targeting CXCL13 for the treatment of immune-mediated inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Sepsis, a severe inflammatory response to infection, is a global health priority due to its high mortality and long-term disability rates. Its pathophysiology involves both inflammation and immune suppression. Managing sepsis requires significant healthcare resources and expenditure, with sepsis being a leading cause of hospital costs. Gut microbiotas play a crucial role in sepsis, and probiotics show promise in managing it by restoring microbial balance. Despite advances, targeted therapies for sepsis remain elusive, necessitating innovative approaches such as probiotic therapy. Method: Fifty-four eligible patients with sepsis will be randomly assigned to either the synbiotic or placebo group. The synbiotic supplement, KidiLact, comprises ten probiotic strains and prebiotic fructooligosaccharides. Participants will receive two sachets daily for 7 days, mixed with sterile water and administered orally or via gavage. Inflammatory factors including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) will be evaluated. Anthropometric measurements, nutritional assessment, biochemical analysis, and clinical evaluation will be conducted to assess treatment outcomes. Statistical analysis will be performed to compare results between the two groups, employing SPSS version 19 with a significance level of P <.05. Conclusion: This randomized clinical trial aims to evaluate synbiotic supplementation effects on inflammatory markers and clinical outcomes in pediatric sepsis patients in the pediatric intensive care unit (PICU). Probiotics have shown promise in reducing proinflammatory cytokines like IL-6, TNF-α, and CRP, which are vital in the inflammatory response. Synbiotics can enhance gut integrity, preventing pathogen translocation and reducing inflammation. If our expectations regarding the effects of probiotics are correct, we can use them as a cost-effective supplement to improve the condition of pediatric sepsis in hospitals. Trial registration: IRCT,IRCT20230523058266N1 Registered 30 October 2023, https://irct.behdasht.gov.ir/trial/71397. [ABSTRACT FROM AUTHOR]

Background: Age-related reproductive aging is a natural and irreversible physiological process, and delaying childbearing is increasingly common all over the world. Transplantation of mesenchymal stem cells (MSCs) is considered a new and effective therapy to restore ovarian function, but the relevant mechanisms remain unclear. Recently, it has been found that there is a local Renin–angiotensin system (RAS) in human ovary and it plays a key role. Methods: After collecting follicular fluid from women who received oocyte retrieval for pure male factor infertility, the level of RAS components in it were detected, and the correlation analysis by linear regression. Then, the in vivo experiments on female C57BL/6 mice were designed to measure ovarian function, and the transcription and translation levels of RAS pathway were detected by molecular biology methods. Moreover, the role of RAS in regulating inflammation and oxidative stress in the co-culture system were explored in in vitro experiments on KGN cells. Results: First, a total of 139 samples of analyzable follicular fluid were obtained. The local RAS of ovary, which is independent of systemic RAS (P > 0.05), is affected by age (Pearson r < 0, P < 0.05) and related to ovarian function, inflammation, oxidative stress indexes and assisted reproduction laboratory outcomes (P < 0.05). Next, the ovary/body weight of aging mice decreased significantly and serum sex hormones levels changed significantly (P < 0.01). The number of functional follicles decreased, while the atresia follicles increased (P < 0.05). After MSCs transplantation, all the above measures have been partially recovered (P < 0.05). Although several RAS components in aging ovary changed, MSCs only improved the expression level of AT1R (P < 0.05). Furthermore, the secretion ability and mitochondrial membrane potential of aging KGN cells decreased, while the intracellular ROS level and the aging cells ratio increased (P < 0.01). All the above measures have been partially recovered when co-cultured with MSCs (P < 0.05). After Ang(1–7) were added into the co-culture system, the above have been more significantly restored compared with Ang II (P < 0.05). Nevertheless, there was no statistical difference in estradiol level no matter which one was added (P > 0.05). Conclusions: Together, our findings indicate that a novel possible mechanism to explain how stem cells restore age-related ovarian functional decline. [ABSTRACT FROM AUTHOR]

Introduction: Nuclear factor kappa B (NF-κB) is a key regulator of immune and inflammatory responses. Glucocorticoid drugs (GC) act through the glucocorticoid receptor (GR) as immunosuppressant also in pediatric patients inhibiting NF-κB activity. The long non-coding RNA GAS5 interacts with the GR, influencing GC activity. No data on the role of GAS5 on GR-dependent inhibition of NF-κB activity have been published. Methods: This study investigated the impact of GAS5 on NF-κB activity in HeLa cells overexpressing GAS5, both under basal conditions and during GC treatment. The study used EMSA, RNA-immunoprecipitation (RIP), Western blotting, and bioinformatic analyses to assess NF-κB DNA binding, GAS5-p65 interaction, and NF-κB signaling pathway modulation. Results: GAS5 overexpression increased NF-κB DNA binding activity in untreated cells. RNA-IP confirmed a direct interaction between GAS5 and the NF-κB subunit p65, suggesting a potential regulatory mechanism. GAS5 overexpression led to downregulation of NF-κB target genes, TNF-a, and NR3C1. GC treatment reduced NF-κB DNA binding activity in GAS5-overexpressing cells, indicating a potential synergistic effect. Furthermore, GAS5 overexpression increased IκB levels and reduced p-p65/pan-p65 levels during GC treatment. Discussion: GAS5 appears to modulate NF-κB activity in a complex manner, influencing both basal and GC-induced signaling. The interaction between GAS5, GCs, and NF-κB is multi-faceted, and further research is needed to fully elucidate the underlying mechanisms. These findings suggest that GAS5 could be a potential target for personalized therapy, particularly in pediatric patients with inflammatory conditions. [ABSTRACT FROM AUTHOR]

Introduction: Macrophages play a key role in most of the inflammatory diseases such as Rheumatoid Arthritis (RA), but the mechanism underlying their pathogenesis is still under study. Among stem cells, human dental pulp stem cells (hDPSCs) have attracted attention due to their easy accessibility and immunomodulatory properties, making them a promising adjuvant therapy. In this study, we aimed to evaluate the capacity of hDPSCs to modulate the phenotypes of primary human macrophages. Additionally, we sought to observe the differences induced on macrophages when cultured directly with hDPSCs or through a cell culture insert, mimicking the paracrine communication pathway. Methods: Monocytes, isolated from buffy coats, were differentiated into proinflammatory M1 and anti-inflammatory M2 macrophages. Subsequently, they were cultured with hDPSCs either directly or via a cell-culture insert for 48 hours. Finally, they were analyzed for protein, gene expression, cytokines levels and immunofluorescence. Results: In our study, we have demonstrated that, hDPSCs, even without priming, can reduce TNFa levels and enhancing IL-10 release in pro-inflammatory macrophages, both through direct contact and paracrine signaling. Furthermore, we found that their effects are more pronounced when in cell-to-cell contact through the decrease of NF-kB and COX-2 expression and of CD80/PD-L1 colocalization. HDPSCs, when in contact with macrophages, showed enhanced expression of NF-kB, COX-2, ICAM-1, PD-L1, FAS-L, TNFa and IFNg. Conclusion: We showed that hDPSCs exert immunomodulatory effects on proinflammatory macrophages, with cell-to-cell contact yielding a more pronounced outcome compared to paracrine signaling. Our work highlights the immunomodulatory properties of hDPSCs on activated pro-inflammatory macrophages and the potential therapeutic role in inflamed tissue. [ABSTRACT FROM AUTHOR]

Background: Extensive observational data suggest a link between celiac disease (CeD) and osteoporosis, but the causality and mediating mechanism remain undetermined. Herein, we performed a Mendelian randomization (MR) study to address these concerns. Methods: We obtained the summary-level statistics for CeD from a large genome-wide association study (GWAS) comprising 4,533 cases and 10,750 controls of European ancestry. The GWAS data for osteoporosis-related traits and inflammatory cytokines were derived from the UK Biobank, FinnGen, IEU OpenGWAS database, or GWAS catalog. Two-sample MR with the inverse variance-weighted methods were employed to evaluate the genetic association between CeD and osteoporosis-related traits. The potential inflammatory mediators from CeD to osteoporosis were explored using twostep mediation analyses. Results: The primary MR analyses demonstrated causal associations between genetically predicted CeD and osteoporosis (odds ratio [OR]: 1.110, 95% confidence interval [CI]: 1.043-1.182, p=0.001), total body bone mineral density (β: -0.025, p=0.039), and osteoporotic fracture (OR: 1.124, 95% CI: 1.009-1.253, p=0.034). Extensive sensitivity analyses consolidated these findings. Among the candidate inflammatory cytokines, only interleukin-18 was observed to mediate the effects of CeD on osteoporosis, with an indirect OR of 1.020 (95% CI: 1.000-1.040, p=0.048) and a mediation proportion of 18.9%. The mediation effects of interleukin-18 could be validated in other datasets (OR: 1.015, 95% CI: 1.001-1.029, p=0.041). Bayesian colocalization analysis supported the role of interleukin-18 in osteoporosis. Conclusion: The present MR study reveals that CeD is associated with an increased risk of developing osteoporosis, which may be partly mediated by upregulation of interleukin-18. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) has reached epidemic proportions worldwide. The consequences of TBI can be severe even with repetitive mild trauma. If death and coma are avoided, the consequences of TBI in the long term typically involve dizziness, sleep disturbances, headache, seizures, cognitive impairment, focal deficits, depression, and anxiety. The severity of brain injury is a significant predictor of outcome. However, the heterogenous nature of the injury makes prognosis difficult. The present review of the literature focuses on the genetics of TBI including genome wide (GWAS) data and candidate gene associations, among them brain-derived neurotrophic factor (BDNF) with TBI and development of post-traumatic epilepsy (PTE). Molecular biomarkers of TBI are also discussed with a focus on proteins and the inflammatory protein IL1-β. The secondary medical sequela to TBI of cognitive impairment, PTE, headache and risk for neurodegenerative disorders is also discussed. This overview of TBI concludes with a review and discussion of the medical management of TBI and the medicines used for and being developed at the preclinical and clinical stages for the treatment of TBI and its host of life-debilitating symptoms. [ABSTRACT FROM AUTHOR]

Objectives: To detect the plasma polyunsaturated fatty acids (PUFAs) concentrations in age-related macular degeneration (AMD) patients and healthy controls. Additionally, advanced studies were conducted to investigate the relationship between PUFAs concentrations and ophthalmological characteristics, including hyperreflective foci (HRF), visual acuity, and anti-vascular endothelial growth factor (anti-VEGF) response in patients with AMD. Methods: This prospective, single-site study recruited a total of 315 participants, consisting of 105 individuals with dry AMD (early-stage AMD group), 105 individuals with neovascular AMD (late-stage AMD group), and 105 elderly individuals without any fundus diseases (healthy controls). The levels of omega-3 and omega-6 PUFAs in plasma were detected using gas chromatography. Retinal thickness, choroidal thickness, andmacular volume were quantified using optical coherence tomography angiography (OCTA) scan with a 6 x 6 mm macular area, and the amounts of HRF were analyzed with OCTA scanning data. Results: Compared to the control group, AMD patients exhibited significantly lower plasma concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and alpha linolenic acid. HRF were observed in various retinal layers of AMD patients, particularly those with late-stage AMD. The correlation coefficient matrix and multiple linear regression models demonstrated that HRF played a crucial role in best corrected visual acuity for both early (p < 0.001) and late-stage AMD patients (p = 0.006), while EPA had an inverse effect on the logarithm of the minimum angle of resolution (logMAR) value in patients with early-stage AMD (p < 0.001). As compared to patients with good responses to anti-VEGF therapy, those with poor responses had significantly lower baseline logMAR (p < 0.001), central retina thickness (p = 0.002), macular volume (p = 0.027), HRF (p = 0.024), and plasma EPA (p < 0.001). This study used a ROC curve analysis to identify the combination of HRF and EPA as a potential biomarker for predicting the response to anti-VEGF treatment in late-stage AMD patients, with an area under the curve (AUC) value of 0.775. Conclusions: Reduced plasma EPA was detected in AMD cases and the lower EPA concentration was related to poorer visual acuity. Additionally, the quantity of HRF combined with concentration of plasma EPA may serve as the prognostic indicator for predicting the effect of anti-VEGF treatment in late-stage AMD patients. [ABSTRACT FROM AUTHOR]

Infection by bacteria leads to tissue damage and inflammation, which need to be tightly controlled by host mechanisms to avoid deleterious consequences. It is previously reported that TMEM16F, a calcium‐activated lipid scramblase expressed in various immune cell types including T cells and neutrophils, is critical for the control of infection by bacterium Listeria monocytogenes (Lm) in vivo. This function correlated with the capacity of TMEM16F to repair the plasma membrane (PM) damage induced in T cells in vitro, by the Lm toxin listeriolysin O (LLO). However, whether the protective effect of TMEM16F on Lm infection in vivo is mediated by an impact in T cells, or in other cell types, is not determined. Herein, the immune cell types and mechanisms implicated in the protective effect of TMEM16F against Lm in vivo are elucidated. Cellular protective effects of TMEM16F correlated with its capacity of lipid scrambling and augment PM fluidity. Using cell type‐specific TMEM16F‐deficient mice, the indication is obtained that TMEM16F expressed in liver Kupffer cells (KCs), but not in T cells or B cells, is key for protection against Listeria in vivo. In the absence of TMEM16F, Listeria induced PM rupture and fragmentation of KCs in vivo. KC death associated with greater liver damage, inflammatory changes, and dysregulated liver metabolism. Overall, the results uncovered that TMEM16F expressed in Kupffer cells is crucial to protect the host against Listeria infection. This influence is associated with the capacity of Kupffer cell‐expressed TMEM16F to prevent excessive inflammation and abnormal liver metabolism. [ABSTRACT FROM AUTHOR]

Hemorrhagic shock and resuscitation (HSR) enhances the risk of acute lung injury (ALI). This study investigated the protective effect of carbamazepine (CBZ) on HSR-induced ALI in rats. Male Sprague-Dawley rats were allocated into five distinct groups through randomization: control (SHAM), saline + HSR (HSR), CBZ + HSR (CBZ/HSR), dimethyl sulfoxide (DMSO) + HSR (DMSO/HSR), and CBZ + chloroquine (CQ) + HSR (CBZ/CQ/HSR). Subsequently, HSR models were established. To detect tissue damage, we measured lung histological changes, lung injury scores, and wet/dry weight ratios. We measured neutrophil counts as well as assessed the expression of inflammatory factors using RT-PCR to determine the inflammatory response. We detected autophagy-related proteins LC3II/LC3I, P62, Beclin-1, and Atg12-Atg5 using western blotting. Pretreatment with CBZ improved histopathological changes in the lungs and reduced lung injury scores. The CBZ pretreatment group exhibited significantly reduced lung wet/dry weight ratio, neutrophil aggregation and number, and inflammation factor (TNF-α and iNOS) expression. CBZ changed the expression levels of autophagy-related proteins (LC3II/LC3I, beclin-1, Atg12-Atg5, and P62), suggesting autophagy activation. However, after injecting CQ, an autophagy inhibitor, the beneficial effects of CBZ were reversed. Taken together, CBZ pretreatment improved HSR-induced ALI by suppressing inflammation, at least in part, through activating autophagy. Thus, our study offers a novel perspective for treating HSR-induced ALI. [ABSTRACT FROM AUTHOR]

Licorice is a therapeutic herb in traditional Chinese herbal medicine. Licorice is considered as an anti‐inflammatory agent due to its suppression and inhibition of inflammatory pathways. Licorice has many bioactive compounds such as glycyrrhetinic acid, glycyrrhizin, liquiritigenin, and isoliquirtigenin which are principally accountable for its therapeutic benefits. These bioactive components reduce inflammation by preventing the activation of important inflammatory pathways including mitogen‐activated protein kinases (MAPKs) and nuclear factor‐kappa B (NF‐κB). As a result of this tumor necrosis factor‐alpha (TNF‐α), interleukin‐1 beta (IL‐1β) and interleukin‐6 (IL‐6) are among the proinflammatory cytokines whose production is inhibited. Components present in licorice inhibit the activation by suppressing the IκBα phosphorylation and degradation. Moreover, licorice compounds also attenuate the MAPK signaling cascades by inhibiting the MAPK kinase phosphorylation and downstream MAPKs such as extracellular signal–regulated kinase (ERK), p38 MAPK, and c‐Jun N‐terminal kinase (JNK). The present review focuses on the current understanding of licorice effect on the NF‐κB and MAPK inflammatory cell signaling pathways at molecular level. Furthermore, emerging evidence suggested that licorice‐derived bioactive compounds may attenuate the molecular mechanism which is associated with inflammation, providing the additional insights into the therapeutic potential. Further studies explained the precise molecular mechanism at the cellular level underlying the licorice anti‐inflammatory effect and potential application in managing inflammatory disorders. In conclusion, licorice has a complex mode of action and is a valuable natural anti‐inflammatory. Its natural origin and effectiveness in clinical applications make it an intriguing topic for additional study. As licorice becomes more widely used in medicine, future research should focus on refining its formulations to optimize therapeutic advantages. [ABSTRACT FROM AUTHOR]

Vaginal infections are a public health problem associated with serious health complications due to the exacerbated inflammation they generate. Vaginal inflammation may also occur in some noninfectious processes, such as noninfectious vaginitis and cytolytic vaginosis. Immune system cells respond to infections through various mechanisms, such as the formation of extracellular traps (ETs), which are DNA networks associated with effector proteins. Many pathogens induce ETs formation in vitro, as occurs in some natural infections. A recent report indicates that human vaginal infections in vivo generate ETs. Therefore, in this study, we aimed to identify ETs in samples from 40 donors who were diagnosed with infectious (i.e., bacterial vaginosis, candidiasis and trichomoniasis) and noninfectious (i.e., noninfectious vaginitis and cytolytic vaginosis) vaginal inflammation. We were able to observe ETs by identifying the LL‐37 peptide, which is associated with DNA networks. In seven vaginal swabs from the control group (formed by 19 donors without vaginal infection symptoms), we detected at least one pathogen per sample and observed ETs; thus, these donors were considered asymptomatic. The remaining 12 donors were confirmed to be healthy, as their exudates did not present any tested pathogens, sign of inflammation or ETs. ETs in vaginal inflammatory processes can worsen inflammation but may also help control infection. [ABSTRACT FROM AUTHOR]

In the present review, we focused on recent translational and clinical discoveries in asthma immunology, facilitating phenotyping and stratified or personalized interventions for patients with this condition. The immune processes behind chronic inflammation in asthma exhibit marked heterogeneity, with diverse phenotypes defining discernible features and endotypes illuminating the underlying molecular mechanisms. In particular, two primary endotypes of asthma have been identified: "type 2-high," characterized by increased eosinophil levels in the airways and sputum of patients, and "type 2-low," distinguished by increased neutrophils or a pauci-granulocytic profile. Our review encompasses significant advances in both innate and adaptive immunities, with emphasis on the key cellular and molecular mediators, and delves into innovative biological and targeted therapies for all the asthma endotypes. Recognizing that the immunopathology of asthma is dynamic and continuous, exhibiting spatial and temporal variabilities, is the central theme of this review. This complexity is underscored through the innumerable interactions involved, rather than being driven by a single predominant factor. Integrated efforts to improve our understanding of the pathophysiological characteristics of asthma indicate a trend toward an approach based on disease biology, encompassing the combined examination of the clinical, cellular, and molecular dimensions of the disease to more accurately correlate clinical traits with specific disease mechanisms. [ABSTRACT FROM AUTHOR]

The presence of microplastics within the human body has raised significant concerns about their potential health implications. Numerous studies have supported the hypothesis that the accumulation of microplastics can trigger inflammatory responses, disrupt the microbiome, and provoke immune reactions due to their physicochemical properties. Chronic inflammation, characterized by tissue damage, angiogenesis, and fibrosis, plays a crucial role in cancer development. It influences cancer progression by altering the tumor microenvironment and impairing immune surveillance, thus promoting tumorigenesis and metastasis. This review explores the fundamental properties and bioaccumulation of microplastics, as well as their potential role in the transition from chronic inflammation to carcinogenesis. Additionally, it provides a comprehensive overview of the associated alterations in signaling pathways, microbiota disturbances, and immune responses. Despite this, the current understanding of the toxicity and biological impacts of microplastics remains limited. To mitigate their harmful effects on human health, there is an urgent need to improve the detection and removal methods for microplastics, necessitating further research and elucidation. [ABSTRACT FROM AUTHOR]

Hypertension is associated with poor outcome and higher mortality in patients with ischemic stroke. The impairment of adaptive vascular mechanisms under hypertensive condition compromises collateral blood flow after arterial occlusion in patients with acute ischemic stroke resulting in hypoperfusion. The increased oxidative stress caused by hypoperfusion is thought to be a trigger for the rapid evolution of ischemic infarct volume under hypertensive condition. However, the cellular factors and pathways that contribute to the exacerbation of ischemic brain injury under hypertensive condition is not yet understood. The current study reveals that predisposition to hypertension leads to basal loss of function of the neuron-specific tyrosine phosphatase STEP, which plays a crucial role in neuroprotection against excitotoxic insult. The findings further show that a mild ischemic insult in hypertensive rats triggers an early onset and sustained activation of the neuronal extracellular signal regulated kinase (ERK MAPK), a member of the mitogen activated protein kinase family and a substrate of STEP. This leads to rapid increase in the activation of neuronal NF-κB, expression of neuronal cyclooxygenase-2 and subsequent biosynthesis of the pro-inflammatory mediator prostaglandin E2, resulting in rapid morphological transformation of microglia to the pro-inflammatory state and subsequent exacerbation of ischemic brain injury. Restoration of STEP signaling with intravenous administration of a STEP-derived peptide mimetic reduces the pro-inflammatory response in neurons, activation of microglia, and ischemic brain injury. The findings suggest that the basal loss of STEP function under hypertensive condition contributes to the exacerbation of ischemic brain injury by enhancing post-ischemic inflammatory response. The study not only presents a novel role of STEP in regulating neuroimmune communication but also highlights the therapeutic potential of a STEP-mimetic in mitigating ischemic brain damage under hypertensive condition. [ABSTRACT FROM AUTHOR]