Inflammatory Disorders Research Articles

Phthalocyanine derivative attenuates TNF-α production in macrophage culture and prevents alveolar bone loss in experimental periodontitis.

This study investigated the activity and mechanism of action of the iron tetracarboxyphthalocyanine (FeTcPc) on tumor necrosis factor alpha (TNF-α) production and its impact on experimental periodontitis. RAW 264.7 macrophages were treated with FeTcPc, activated with lipopolysaccharide (LPS) at 10 ng/mL, and the TNF-α levels were measured, as well as the nuclear factor kappa B (NF-κB) activation. Subsequently, a mouth gel containing 1% FeTcPc was topically administered to the gingival tissue of mice with periodontitis-induced ligatures. Bone loss and the gene expression of Tnfα, p65 (NF-κB), and receptor-activating nuclear factor kappa B ligand (Rankl) were quantified in gingival tissue. Finally, the systemic toxicity of FeTcPc was estimated in Galleria mellonella larvae. In an activated RAW 264.7 macrophage culture, 100 μM FeTcPc reduced TNF-α release and NF-κB activation. Regarding experimental periodontitis, topical application of mouth gel containing 1% FeTcPc blocked alveolar bone loss. Additionally, 1% FeTcPc reduced the expression of Tnfα, p65 (NF-κB), and Rankl in gingival tissue. Finally, administration FeTcPc at doses ranging from 1 to 1000 mg/kg did not cause acute systemic toxicity in G. mellonella. Overall, we demonstrated the potential of mouth gel containing FeTcPc as a therapeutic strategy for managing osteolytic inflammatory disorders, such as periodontitis.

Superior effect of adalimumab versus secukinumab on ultrasound-confirmed synovitis in psoriatic arthritis: comprehensive evidence from musculoskeletal ultrasound and clinical assessments

Background and objectives: Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disorder affecting 30% of psoriatic patients. Effective treatment, especially with biologics like IL-17 and TNF inhibitors, is vital for improving patient outcomes. This study aimed to compare the efficacy of secukinumab and adalimumab in PsA patients through clinical and ultrasonographic evaluations.Materials and methods: We enrolled 116 PsA patients, with 58 patients receiving secukinumab and 58 receiving adalimumab. Regular follow-ups were conducted at weeks 4, 12, 24, and 52. The primary outcome was the proportion of patients achieving at least a 20% improvement in the ACR response (ACR20) at week 12, with additional evaluations for axial arthritis, enthesitis, skin involvement, minimal disease activity, health assessment questionnaire, and ultrasound changes.Results: There was no significant difference in ACR20 response between the two groups at week 12 (OR: 0.59, 95% CI: 0.26–1.37, p = 0.22). However, secukinumab demonstrated superior efficacy in achieving Psoriasis Area and Severity Index (PASI)90 (OR: 2.25, 95%CI: 1.07–4.74, p = 0.03), while adalimumab showed better improvement in ultrasound synovitis count (β: 0.94, 95%CI: 0.09–1.79, p = 0.03) and synovitis PD signal (β: 0.20, 95%CI: 0.03–0.36, p = 0.02).Conclusions: In conclusion, both treatments were highly effective for PsA, with secukinumab being more suitable for severe skin involvement and adalimumab for significant ultrasound-confirmed synovitis.

Microenvironment-Activatable Probe for Precise NIR-II Monitoring and Synergistic Immunotherapy in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) represents an insidious autoimmune inflammatory disorder that severely lowers the life quality by progressively destructing joint functions and eventually causing permanent disability, posing a serious public health problem. Here, an advanced theranostic probe is introduced that integrates activatable second near-infrared (NIR-II) fluorescence imaging for precise RA diagnosis with multi-pronged RA treatments. A novel molecular probe comprising a long-wavelength aggregation-induced emission unit and a manganese carbonyl cage motif is synthesized, which enables NIR-II fluorescence activation and concurrently releasing therapeutic carbon monoxide (CO) gas in inflamed joint microenvironment. This molecular probe self-assembles into a biocompatible nanoprobe, which is subsequently conjugated with anti-IL-6R antibody to afford active-targeting ability of RA. The nanoprobe exhibits significant turn-on NIR-II fluorescence signal at the RA lesion, enabling highly sensitive RA diagnosis and real-time therapeutic monitoring. The combination of ROS scavenging, on-demand CO gas release, and IL-6 signaling blockade results in potent therapeutic effect and synergistic immunomodulation impact, significantly alleviating the RA symptoms and preventing joint destruction. This research introduces a novel paradigm for the development of high-performance, activatable theranostic strategies to facilitate precise detection and enhanced treatment of RA-related diseases.

Immuno-therapeutic and prophylactic potential of Trichinella spiralis antigens for inflammatory bowel diseases

Ulcerative colitis (UC), a severe chronic inflammatory disorder of the colon, is one of the inflammatory bowel diseases (IBD) that affects humans and several domestic animal species, including cats and dogs. Helminth infections and autoimmune diseases are inversely correlated, as explained by the hygiene hypothesis, which suggests that IBD is infrequent in countries where helminth infections are common but more prevalent in developed nations. This study investigated the therapeutic and prophylactic potential of Trichinella spiralis (T. spiralis) antigens in an experimental colitis model for IBD. Mice were divided into eight groups: normal model, colitis model, larval antigen prophylaxis, adult antigen prophylaxis, larval antigen therapeutic, adult antigen therapeutic, larval antigen prophylaxis and therapeutic, and adult antigen prophylaxis and therapeutic. Colitis was induced intrarectally by administering a single dose of 0.2 ml of acetic acid, except in the healthy group, which received PBS (0.2 ml). The mice were euthanized 12 days after colitis induction. The therapeutic and prophylactic potential of T. spiralis antigens were assessed through colitis severity and histopathological, immunological, and immunohistochemical examinations. The results showed a significant reduction in Disease Activity Index (DAI), an increase in goblet cells' acidic mucin levels, reduced iNOS and TNF-α expression, and decreased serum levels of IFN-γ and IL-10 cytokines in Groups IV-VIII compared to the colitis model, particularly in the group that received adult worm antigen both prophylactically and therapeutically. This study demonstrated that T. spiralis antigens, especially from adult worms, had protective and therapeutic effects on experimental colitis, with a superior effect when administered both before and after colitis induction by reducing inflammation and modulating the immune response. Thus, T. spiralis antigens may improve disease outcomes and provide a novel treatment approach for ulcerative colitis.

Defensins in Periodontics: A Comprehensive Review

Periodontal diseases, such as gingivitis and periodontitis, are inflammatory disorders that impact the tissues supporting the teeth. These diseases are initiated by bacterial plaque biofilms that form on the tooth surface. The host's immune response to this bacterial challenge plays a crucial role in disease progression. Among the various components of the immune system, antimicrobial peptides (AMPs) such as defensins have gained significant attention for their role in maintaining oral health and their potential therapeutic applications in periodontics. This review article explores the biology, function, and therapeutic potential of defensins in periodontal health and disease.

7944 Elevated Serum Alkaline Phosphatase without other Abnormalities of Liver Associated Enzymes as an early Indicator of Glucose Intolerance: A Case Series

Abstract Disclosure: B.K. Bowens: None. C. Godar: None. D. LaChance: None. T.D. Hoang: None. M.K. Shakir: None. Glucose intolerance (GI) is defined as dysglycemia and includes impaired fasting glucose, impaired glucose tolerance, and prediabetes. Early detection of GI could lead to appropriate treatment and delay the progression to diabetes mellitus. The cases below detail two patients with elevated serum alkaline phosphatase (ALP) without other liver-associated enzyme abnormalities as an early indicator of GI. Case 1: A 54-year-old woman with a history of multinodular goiter status post thyroidectomy (2020), adrenal incidentaloma (2016), and asthma was incidentally found to have an elevated HbA1C (A1C) of 6.3% on screening labs in 2015. At that time, her ALP was 73 IU/L (ref 44−121). Her ALP levels slowly rose from 88 to 152 IU/L by September 2020. Work up did not reveal any etiological factors for the elevated ALP. One month later, HbA1C was found to be 7.6%. Metformin was initiated with improvement in A1C to 6.3% with an ALP of 130 IU/L. However, metformin was discontinued due to intolerance. In April 2023, her A1C was 9.3% with an ALP of 134 IU/L. A1C rose to 12.8% in Jun 2023 at which time she was started on insulin glargine, insulin aspart, sitagliptin, and was restarted on metformin. Her A1C decreased to 8.6% in August 2023 with normalization of ALP to 88 IU/L. Case 2: A 53-year-old woman with a history of hypertension, hyperlipidemia, obstructive sleep apnea, and non-ischemic cardiomyopathy in 2004 was found to have an elevated A1C of 5.8% on her screening labs in Jun 2019. Her ALP was notably in the high-normal range until Oct 2021 when it was found to be 138 IU/L. Her most recent A1C was 5.9% with an ALP of 142 IU/L. The patient was started on semaglutide (WegovyTM) briefly but was unable to tolerate the side effects. She was then started on metformin 500mg BID and dulaglutide with normalized ALP level. Discussion: Emerging evidence has shown that serum ALP activity is modestly increased in cardiometabolic diseases such as type 2 diabetes, dyslipidemia, hypertension, and peripheral arterial disease. These are increasingly being considered as inflammatory disorders and it has been shown that serum ALP level was positively and independently associated with metabolic syndrome both in men and women. It is possible that ALP could be an indicator of non-alcoholic fatty liver disease (NAFLD) which is associated with GI. Typically, NAFLD presents with higher ALT and GGT, however, occasionally isolated enzyme elevations or no elevated enzymes at all may occur. Conclusion: These cases suggest that an isolated elevation in ALP could be indicative of GI. Patients incidentally found to have an elevated ALP should be worked up further for possible evidence of GI. Early detection of GI could delay progression to diabetes and decrease morbidity. Presentation: 6/1/2024

Tulipalin A suppressed the pro-inflammatory polarization of M1 macrophage and mitigated the acute lung injury in mice via interference DNA binding activity of NF-κB

Acute lung injury (ALI) is an inflammatory disorder accompanied by higher morbidity and mortality. The pathological mechanism of ALI has been reported to be associated with the release of inflammatory cytokines by macrophages. Sesquiterpene lactones (SLs) represent the principal anti-inflammatory components of many natural products. Tulipalin A is a natural small molecule and a conserved moiety in anti-inflammatory SLs. However, the anti-inflammatory potential of Tulipalin A has yet to be fully disclosed. The present study aims to investigate TulipalinA's anti-inflammatory activity and underlying mechanisms in vitro and in vivo. Tulipalin A suppressed inflammatory responses in lipopolysaccharide (LPS)-stimulated bone marrow-derived primary macrophages and ameliorated LPS-induced ALI in mice. Mechanistically, Tulipalin A directly targets the NF-κB p65 and disrupts its DNA binding activity, thereby impeding the activation of NF-κB. Inhibition of NF-κB attenuated M1 polarization of macrophages, consequently suppressing the production of pro-inflammatory mediators and ameliorating the onset and progression of ALI. These findings suggest Tulipalin A's potential to mitigate inflammatory disorders like ALI via targeting NF-κB p65 and disrupting its DNA binding activity.

Enhanced Transcription of Human Endogenous Retroviruses and TRIM28 Downregulation in Patients with Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) includes patients affected by Crohn's disease or ulcerative colitis. IBD is thought to be a chronic immune-mediated disease, but its origin remains elusive, and this limits new therapeutic approaches. Human endogenous retroviruses (HERVs) originate from ancestral infections and represent 8% of the human genome. HERVs are no longer infectious, but some retroviral sequences can be activated, and their aberrant expressions have been implicated in inflammatory and autoimmune disorders. HERV transcription is regulated by TRIM28 and SETDB1, which are also directly involved in epigenetic processes and modulation of the immune response. Using a PCR real-time Taqman amplification assay, we assessed, for the first time, the transcription levels of pol genes of HERV-H, -K, and -W families of env genes of syncytin 1 (SYN1), SYN2, and HERV-W, as well as of TRIM28 and SETDB1 in the whole blood of 48 patients with Crohn's disease (CD), 20 with ulcerative colitis (UC), and in healthy controls (HC) of comparable age. The transcriptional levels of HERV-H-pol (p = 0.0003) and HERV-K-pol (p = 0.001) were significantly higher in IBD patients compared with HC, with no differences between patients with CD and UC. No significant differences were found for the remaining HERVs between IBD patients and HC. The transcript levels of TRIM28 were significantly downregulated in IBD patients (p < 0.001), without differences between CD and UC, while the SETDB1 levels were preserved. The enhanced transcription of HERV-H-pol and HERV-K-pol, as well as the impaired activation of TRIM28, were not influenced by clinical disease activity and type of treatment. The overexpression of HERVs and impaired transcription of TRIM28 in patients affected by CD or UC suggest that they might be the main actors in the pathophysiology of IBD, opening the way to innovative targeted interventions.

Macular Star and Neuroretinitis with Optic Disk Edema

Neuroretinitis is an inflammatory disorder of the eye presenting with unilateral visual loss, optic disc edema, and subsequent formation of a macular star. Neuroretinitis can be classified as idiopathic, infectious and recurrent. Following a detailed patient history, essential work-up should include Bartonella antibody titers, the rapid plasma reagin (RPR) test, the tuberculin skin test, ACE and lysozyme levels, and a two-view chest X-ray. Among infectious etiologies of neuroretinitis, cat scratch disease caused by Bartonella henselae is the most frequently observed, accounting for two-thirds of cases. Recurrent neuroretinitis is characterized by poorer visual recovery and visual field loss. Patients should be informed about the possibility of recurrence to prevent severe vision loss.

N6-methyladenosine modification-tuned lipid metabolism controls skin immune homeostasis via regulating neutrophil chemotaxis.

Disrupted N6-methyladenosine (m6A) modification modulates various inflammatory disorders. However, the role of m6A in regulating cutaneous inflammation remains elusive. Here, we reveal that the m6A and its methyltransferase METTL3 are down-regulated in keratinocytes in inflammatory skin diseases. Inducible deletion of Mettl3 in murine keratinocytes results in spontaneous skin inflammation and increases susceptibility to cutaneous inflammation with activation of neutrophil recruitment. Therapeutically, restoration of m6A alleviates the disease phenotypes in mice and suppresses inflammation in human biopsy specimens. We support a model in which m6A modification stabilizes the mRNA of the lipid-metabolizing enzyme ELOVL6 via the m6A reader IGF2BP3, leading to a rewiring of fatty acid metabolism with a reduction in palmitic acid accumulation and, consequently, suppressing neutrophil chemotaxis in cutaneous inflammation. Our findings highlight a previously unrecognized epithelial-intrinsic m6A modification-lipid metabolism pathway that is essential for maintaining epidermal and immune homeostasis and lay the basis for potential therapeutic targeting of m6A modulators to attenuate inflammatory skin diseases.

Investigating interferon type I responses in patients with suspected giant cell arteritis and polymyalgia rheumatica.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely related inflammatory disorders. Easily measurable biomarkers defining active disease and identifying patients in need of glucocorticoid sparing treatment options are highly desired. Interferon Type I (IFN-I) might be involved in disease pathology; however, evidence is limited. This study explores a systemic IFN-I signature and expression of IFN-I markers in GCA and PMR patients. Treatment naive GCA and PMR patients, and PMR patients with glucocorticoid treatment were included. Patients suspected of but not diagnosed with GCA were used as controls. Five relevant IFN-I-stimulated genes were identified in literature, and relative expression levels were determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR) in peripheral blood mononuclear cells. An IFN-I score was generated. Serum levels of IFN-I induced C-X-C motif chemokine 10 (CXCL10) and Galectin-9 were determined by multiplex immunoassay. There were no differences in IFN-I scores between the groups. An IFN-I signature was observed in 0/9 controls, 2/11 GCA patients, 4/20 treatment naive PMR patients, and 2/10 PMR patients with treatment. Serum CXCL10 and Galectin-9 were not increased in GCA or PMR patients compared to control patients. Treated PMR patients had lower CXCL10 levels [423.2 pg/ml (375.1-491.1)] compared to treatment naive PMR patients [641.8 pg/ml (552.8-830.6)]. An IFN-I signature does not distinguish GCA and PMR patients from controls. Also, IFN-I-induced serum markers are not upregulated in GCA and PMR patients. Easily measurable IFN-I-induced serum markers will therefore probably not aid in diagnosis and additional treatment options in newly diagnosed GCA and PMR patients.

Chrysophanol: A Promising Agent in Modulating Inflammatory Pathways

Chrysophanol, a naturally occurring anthraquinone compound found in various plants, fungi, and lichens, has garnered increasing attention for its potential therapeutic benefits, particularly in the context of inflammation-related disorders. This review aims to provide a comprehensive overview of the anti-inflammatory properties of chrysophanol and its potential as a therapeutic agent for intervention in inflammatory conditions. In this review, the current understanding of the molecular mechanisms underlying the anti-inflammatory effects of Chrysophanol, including its modulation of key inflammatory signaling pathways, such as NF- κB, MAPK, JAK-STAT, Nrf2, and other NLRP3 inflammasomes. Additionally, we discuss the evidence from in vitro and in vivo studies supporting the anti-inflammatory efficacy of chrysophanol in various experimental models of inflammation, including various inflammatory diseases. Furthermore, we explore the pharmacokinetic profile of Chrysophanol and other nanoformulations to understand its therapeutic potential. Overall, accumulating evidence suggests that chrysophanol holds promise as a novel therapeutic candidate for the management of inflammatory disorders, warranting further investigation and clinical translation.

IVIG response in pediatric acute-onset neuropsychiatric syndrome correlates with reduction in pro-inflammatory monocytes and neuropsychiatric measures.

Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is characterized by abrupt onset of obsessive-compulsive disorder or eating restriction along with the abrupt onset of other co-occurring symptoms (tics, behavioral and cognitive regression, etc.). PANS is thought to be a post-infectious immunopsychiatric disorder, although as with most post-infectious disorders, it is challenging to establish a causal relationship with proposed infectious triggers. Intravenous immunoglobulin (IVIG) can modulate inflammation and support the elimination of infection and has been used for treatment of many post-infectious inflammatory disorders and autoimmune conditions. The aim of the study is to explore the pro-inflammatory state in PANS before and after administration of IVIG. Children with moderate-to-severe PANS received six infusions of IVIG (Octagam 5%, Octapharma) every 3 weeks with post treatment follow-up. Blood samples and psychiatric measures were obtained at Visits 1 (pre-treatment), 7 and 8 (4 and 11 weeks after last infusion, respectively). Myeloid cell activation was assessed via flow cytometry. All ten patients included in the study were male, White, with mean age 12.4 years (range 6-16). Statistically significant improvements following IVIG treatment were demonstrated in all psychometric assessments and parent questionnaires including CY-BOCS (obsessive compulsive scale), YGTSS (tic scale) and a parent PANS rating scale (for all scales p<0.001). The fraction of pro-inflammatory monocytes and dendritic cells decreased from pre-IVIG treatment levels. The proportional reductions were not compensated by increases in total white blood cells; pro-inflammatory monocytes post-IVIG were decreased as a proportion of CD14+ myeloid cells and in absolute number. The results of this study suggest that active PANS is associated with a pro-inflammatory state. This pro-inflammatory profile and psychometric scores improved following IVIG treatment. Future work will aim to further elucidate the roles of innate and adaptive immune responses in PANS and the regulatory mechanism(s) of IVIG in PANS treatment.

Betulin-NLC-hydrogel for the Treatment of Psoriasis-like Skin Inflammation: Optimization, Characterisation, and In vitro and In vivo Evaluation.

Psoriasis is a chronic inflammatory skin disorder that poses significant challenges regarding effective and targeted drug delivery. Bioactive substances like betulin have shown tremendous utility in treating these conditions; however, they pose limited utility owing to their physicochemical characteristics. Here, we aimed to develop a novel topical dosage form for treating psoriasis, utilising betulin-loaded solid lipid nanoparticles (NLCs) incorporated into a hydrogel matrix. The optimization of the formulation was meticulously conducted using a design of experiments methodology, and its diverse physicochemical attributes were thoroughly examined. Evaluating betulin's in vitro release pattern from the NLC-hydrogel demonstrated consistent and regulated drug release properties. Additionally, the formulation demonstrated improved skin penetration abilities as determined by in vitro skin permeation experiments employing Franz diffusion cells- furthermore, the therapeutic effectiveness of the betulin-NLC-hydrogel was assessed by an in vivo experiment carried out using an imiquimod-induced psoriasis-like skin inflammation model in BALB/c female mice. The NLCs exhibited a pH of 5.67±0.86, particle size of 148.16±12.66 nm, and zeta potential of -22.84±2.37 mV, ensuring stability and suitability for topical use. The gel, with a pH of 6.05±0.43 and viscosity of 17550±120 cPs, showed enhanced skin hydration and lipid restoration. Drug release studies indicated a slower release from NLCs and gel, improving skin retention. Stability tests revealed that the formulations were stable at room temperature but not at elevated temperatures. The in vitro safety profile of the formulation revealed no significant adverse effects on HaCaT cell lines. The NLC gel demonstrated significant anti-psoriatic activity, reducing inflammation and cytokine levels. The betulin-NLC-hydrogel formulation exhibited promising characteristics for the topical treatment of psoriasis, showcasing optimised drug delivery, sustained release, and notable therapeutic efficacy. The findings from this study provide a foundation for the potential clinical translation of this innovative topical dosage form for improved psoriasis management.

Natural Skin Care Regimen Improves Clinical Parameters and Quality of Life in Children with Atopic Dermatitis

Background: Atopic dermatitis (AD) is a prevalent, chronic inflammatory skin disorder, characterized by xerosis, itching and recurrent eczematous lesions. The condition also has major psychosocial implications for patients and their families. A daily skincare regimen of gentle cleansing and moisturization is an important part of atopic dermatitis therapy. Objective: This study evaluated the tolerability and efficacy of a nature-based shampoo/wash and moisturizer in children with mild to moderate atopic dermatitis Methods: This open-label study involved 23 children (6 months – 13 years) with atopic dermatitis. A daily skin care regimen of nature-based shampoo/wash and moisturizer was used for 4 weeks. The primary endpoint was tolerability assessed through clinical grading of erythema, dryness and roughness. The study pediatrician graded the eczema condition using the Eczema Area and Severity Index (EASI), and assessments of stratum corneum hydration and transepidermal water loss were performed before and after treatment. Parent/guardian completed two validated quality of life questionnaires. Results: Twenty children completed the study. Clinical evaluations showed significant improvement in subjects’ atopic disease with daily use of nature-based regimen. Significant reduction in dryness and roughness was observed, indicating that both products were well-tolerated. Moisture content and transepidermal water loss measurements showed directional improvements in skin barrier function. Parent/guardian reported significant improvements in quality-of-life assessments. Conclusions: The study demonstrated that nature-based skin care regimen was well tolerated and improved quality of life and skin condition in children with atopic dermatitis and can be used either alone or in adjunction with traditional treatment for disease control.

Infliximab in the Treatment of a Giant Coronary Aneurysm in Behçet's Disease.

Behçet's disease (BD) is a rare, multisystemic inflammatory disorder with a diverse range of manifestations, primarily affecting the mucocutaneous and ocular systems. While vascular involvement is less frequent it can be severe, with coronary aneurysms being particularly rare. We report a 28-year-old male with BD who developed a giant anterior interventricular artery aneurysm. The patient, initially managed with azathioprine and colchicine, presented with acute chest pain and elevated cardiac markers. Imaging revealed a coronary aneurysm measuring 5.03 cm. Due to the inflammatory nature of the aneurysm surgical intervention was initially deferred, and the patient was treated with corticosteroids and cyclophosphamide. Despite these treatments, recurrent symptoms prompted the initiation of infliximab therapy. Administered at 5 mg/kg at weeks 0, 2 and 6, with subsequent doses every two months, infliximab led to a significant reduction in aneurysm size to 3.73 cm. This case highlights the effectiveness of infliximab in managing giant coronary aneurysms associated with BD, demonstrating its potential as a treatment option for severe vascular complications in BD. The substantial reduction in aneurysm size following infliximab therapy underscores the need for further investigation into its role in treating such rare but serious manifestations of BD. A giant coronary aneurysm is a rare complication of Behçet's disease.Infliximab effectively reduced the aneurysm size.Imaging shows a substantial decrease in aneurysm size after infliximab treatment.

Comparative analysis of nasal endoscopic and radiological findings in chronic rhinosinusitis patients

Background: Chronic rhinosinusitis (CRS) is a complex inflammatory disorder causing significant reduction in quality of life and interfere in day to day activity. Accurate diagnosis is crucial for effective management, typically involving nasal endoscopy and CT imaging to assess the extent of sinus involvement. Methods: This prospective observational study was conducted at Jaipur national university institute of medical sciences and research centre from July 2022 to May 2024. It included 75 patients diagnosed with CRS. Subjective quantification of disease was done using SNOT-22 scoring system. Diagnostic evaluations were performed using nasal endoscopy and CT scans, with findings scored according to the Lund-Kennedy and Lund-MacKay systems. Results: The study highlighted a strong correlation between endoscopic and CT findings, with Pearson correlation coefficients of 0.892 and 0.909 for endoscopic vs. SNOT-22 scores and CT vs. SNOT-22 scores, respectively. Discrepancies between the two diagnostic tools were also noted, emphasizing their complementary roles in CRS management. Conclusions: Integrating nasal endoscopy and CT imaging provides a robust framework for diagnosing and managing CRS, allowing for a detailed assessment of both mucosal and anatomical changes. The combined use of these tools enhances the ability to tailor treatment plans effectively.

Pityriasis rubra pilaris with eosinophilia in a young patient: a case report

Introduction and importance: Pityriasis rubra pilaris is a rare inflammatory papulosquamous disorder which manifests in six clinical subtypes affecting both pediatric and adult populations. Presentation of case: A 14-year-old female presented with multiple itchy scaly lesions on her hands and legs which began as vesicles 9 days after birth. Histopathological examination confirmed the diagnosis of pityriasis rubra pilaris. Further investigations revealed significant peripheral and tissue eosinophilia. The patient was treated with oral isotretinoin, which resulted in the resolution of the lesions. Case discussion: It is a rare inflammatory papulosquamous disorder characterized by palmoplantar keratoderma and follicular papules coalescing into distinct plaques characterized by a reddish-orange hue and nonadherent flaking scales. The patients with tissue and/or peripheral eosinophilia are usually older at presentation and more likely to have multisite disease. Our patient, in contrast, is a young female which makes this case noteworthy. Conclusion: This unusual finding of eosinophilia in a young patient underscores the necessity for further research and evaluation to enhance understanding of the pathophysiology of pityriasis rubra pilaris.

Breastfeeding in infancy and cardiovascular disease in middle-aged and older adulthood: a prospective study of 0.36 million UK Biobank participants

BackgroundCardiovascular disease originates in early life. We aimed to investigate the association between breastfeeding in infancy and cardiovascular disease in adult life. MethodsWe followed 364,240 participants from UK Biobank aged 40–73 years from 2006 – 2010 to 2021. Information on breastfeeding in infancy was self-reported by questionnaire. Cox proportional hazard regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the association between breastfeeding and cardiovascular disease in middle-aged and older adulthood. The multivariable Cox models were used by adjusting for the age (used as the time scale), sex, ethnicity, assessment centre, birth weight, multiple birth status, maternal smoking during pregnancy, Townsend deprivation index, smoking status, alcohol drinker status, physical activity, and menopausal status for women. Binary and multinomial multivariable logistic regression models were used to explore the associations of breastfeeding in infancy with cardiovascular disease risk factors including obesity, body composition, metabolic and inflammatory disorders. ResultsDuring a median of 12.6 years of follow-up, we documented 29,796 new cases of cardiovascular disease, including 24,797 coronary heart disease and 6229 stroke. The multivariable adjusted HRs for breastfed versus non-breastfed were 0.94 (95% CI: 0.91, 0.96) for cardiovascular disease, 0.94 (95% CI: 0.91, 0.96) for coronary heart disease, and 0.95 (95% CI: 0.89, 1.01) for stroke. Furthermore, the strength of observed association between breastfeeding and cardiovascular disease seems to decrease with age (P for interaction <0.001), and increase with polygenic risk for cardiovascular disease (P for interaction <0.001). Consistently, breastfeeding in infancy was associated with cardiovascular disease risk factors including lower body mass index 0.92 (95% CI: 0.89, 0.95), body fat percentage 0.85 (95% CI: 0.83, 0.87), android to gynoid fat ratio 0.89 (95% CI: 0.83, 0.96), visceral adipose tissue 0.92 (95% CI: 0.84, 1.01), as well as lower C-reactive protein level 0.95 (95% CI: 0.94, 0.97) and a lower risk of metabolic syndrome 0.89 (95% CI: 0.85, 0.92). ConclusionsBreastfeeding in infancy was associated with a lower risk of cardiovascular disease in middle-aged and older adulthood. Promoting breastfeeding is vital not only for promoting child health, but also for halting the increasing trend of cardiovascular disease in adults.

Preventive effects of coixol, an active compound of adlay seed, in NGF-differentiated PC12 cells against beta-amyloid25-35-induced neurotoxicity.

The health benefits of coixol, an active compound of adlay seed, have attracted certain attention. Adlay seed is often adopted in traditional Chinese medicine for the treatment of various inflammatory disorders. Thus, it is hypothesized that coixol could protect neuronal cells. The preventive effects of coixol against Abeta25-35-induced damage in nerve growth factor-differentiated PC12 cells were explored. Differentiated PC12 cells were treated with coixol at 0.125 μM, 0.25 μM, 0.5 μM, 1 μM, and 2 μM for 48 h. Then, cells were further exposed to Abeta25-35 at 20 μM for 24 h. Coixol treatments at 0.25-2 μM exhibited antiapoptotic effect via increasing Bcl-2 mRNA expression, mitochondrial membrane potential, and Na+-K+ ATPase activity as well as decreasing Bax mRNA expression, caspase-3 activity, and intracellular Ca2+ release. In addition, coixol treatments at 0.25-2 μM alleviated oxidative and inflammatory responses via lowering reactive oxygen species level, increasing glutathione content, promoting the activity of glutathione peroxidase, glutathione reductase, and catalase, decreasing the generation of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and prostaglandin E2. Furthermore, coixol treatments at 0.25-2 μM diminished intracellular Ca2+ release, and restricted nuclear factor kappa B-binding activity and phosphorylation of p65 and p38. Coixol treatments at 0.5-2 μM increased protein generation of nuclear factor E2-related factor 2, and limited protein production of inducible nitric oxide synthase and receptor of advanced glycation end product. Our novel findings suggested that coixol was a compelling agent against beta-amyloid peptide-induced neurotoxicity.