Local Inflammation Research Articles

Promotion of bone osteogenic and regeneration by resveratrol-derived carbon dots in inflammatory environments via a one-step hydrothermal method

In the context of bone fractures, local inflammation complicates the healing process, adversely affecting the recovery of bone defects. This inflammatory response impedes the regenerative potential of stem cells and induces the differentiation of macrophages into the M1 type, thereby inhibiting bone regeneration. To address this issue, we synthesized carbon dots (CDs) using resveratrol and citric acid. These CDs demonstrated excellent water solubility and retained the anti-inflammatory properties of resveratrol. In an inflammatory environment co-cultured with resveratrol carbon dots (RES-CDs), we observed a reduction in inflammatory factors such as iNOS and an increase in anti-inflammatory factors like CD206. Alkaline phosphatase (ALP) activity, Alizarin Red staining, and immunofluorescence assays indicated that MC3T3 cells produced more calcium nodules after co-culture with RES-CDs, along with enhanced expression of bone formation factors BMP-2 and ALP. Additionally, real-time polymerase chain reaction (qRT-PCR) and immunofluorescence analysis demonstrated that RES-CDs could induce bone tissue proliferation and differentiation by upregulating ALP, BMP-2, OCN, and OPN. In a rat cranial defect model, RES-CDs promoted tissue healing and bone proliferation at weeks 1 and 4 post-surgery. These findings underscore the potential of resveratrol carbon dots in promoting bone tissue healing while mitigating inflammation, thereby offering a promising approach for nanocomposite materials in tissue repair.

Hydronephrosis in a Sigmoid Supernumerary Kidney

Supernumerary kidneys are a rare developmental anomaly, often discovered incidentally or during the investigation of complications such as infections or obstructive uropathy. This case report presents a 70-year-old male patient with a sigmoid supernumerary kidney complicated by hydronephrosis and a staghorn calculus. The patient, with a history of poorly controlled hypertension and type 2 diabetes mellitus, was admitted for febrile left lumbar pain and hemodynamic instability. Diagnostic imaging, including renal ultrasound and uro-CT, revealed a major hydronephrosis in the supernumerary kidney caused by an obstructive staghorn calculus, along with signs of advanced local infection and inflammation. This report highlights the critical role of imaging modalities, particularly uro-CT, in diagnosing renal anomalies and planning treatment. We also review the literature on the management of supernumerary kidneys, emphasizing the importance of early detection and appropriate therapeutic intervention to prevent further complications such as renal insufficiency and infection.

Tungsten-rosmarinic acid nanoenzyme with SOD mimetic activity for the treatment of psoriasis by eliminating ROS and relieving inflammation

Psoriasis is a refractory skin disease that seriously affects the physical and mental health of patients. It is easy to relapse and cannot be cured, which seriously harms the physical and mental health of patients. Oxidative stress, driven by increased reactive oxygen species (ROS), plays a critical role in excessive keratinocyte proliferation and local inflammation in psoriasis. In this study, we successfully synthesized a tungsten-rosmarinic acid nanoenzyme (WRA-PEG), which demonstrates promising therapeutic potential for psoriasis. Our findings demonstrate that WRA-PEG effectively scavenges ROS, reduces the proliferation of keratinocytes, and mitigates the release of pro-inflammatory cytokines in vitro. In a psoriasis-like mouse model induced by imiquimod (IMQ), WRA-PEG significantly improved clinical manifestations and prevented recurrence, as evidenced by reduced epidermal thickness and inhibited inflammatory cytokine expression, outperforming traditional treatments like Benvitimod. Bioinformatics analysis revealed the modulation of key inflammatory and oxidative stress-related pathways, highlighting the involvement of crucial genes such as CCL20 and TNFSF10 in its mechanism of action. Furthermore, WRA-PEG exhibited excellent biocompatibility and stability without adverse effects on liver or kidney function. These results underscore the potential of WRA-PEG as a novel therapeutic strategy for managing psoriasis.

Profiling cytokines in peritoneal effluent through a targeted multiplex cytokine panel provides novel insight into the localized proinflammatory processes in patients undergoing peritoneal dialysis.

The number of relevant markers indicating local intraperitoneal inflammation in patients undergoing peritoneal dialysis (PD) is limited. Therefore, this study aimed to evaluate the compatibility of peritoneal effluent (PE) for proteomic analysis and assess its potential utility in immunoprofiling studies. This pilot study included six PD patients from the Peritoneal Dialysis Center, Department of Nephrology, Transplantology, and Internal Medicine in Szczecin, Poland. All patients were clinically stable, with no signs of infections or malignancy at the time of study. PE samples were collected during routine surveillance visits at the Peritoneal Dialysis Center. Proteomic analysis of the samples was conducted using the Olink® (Olink Proteomics AB, Uppsala, Sweden) Target 48 Cytokine panel. PE samples were successfully analyzed, with 28 out of 45 proteins found within the limit of quantitation (LOQ) and 32 out of 45 proteins detected above the limit of detection (LOD). No significant interference from the matrix was observed in the assay. Biomarkers associated with low-grade inflammation showed varied levels, and the observed patterns were comparable across all patients. This study suggests that utilizing a cytokine panel with relative quantification is a promising method for PE immunoprofiling.

Type 3c diabetes mellitus: what are we dealing with? Review

The authors presented updated data on the term «type 3 diabetes mellitus», its modern classification, pathophysiological mechanisms of development and features of treatment, its definitions, epidemiology and modern classification based on the recommendations of the American Diabetes Association. Definitions and epidemiological features of acute pancreatitis and its most frequent complications, including 3c type diabetes have been described. Statistical data were presented on the risk of developing complications of acute pancreatitis in the form of carbohydrate metabolism disorders. Historical prerequisites of fatal complications of acute pancreatitis in the form of hyperglycemic states were also described. The pathophysiological mechanisms of the development of type 3c diabetes, namely local and systemic inflammation, loss of islet tissue of the pancreas, dysregulation of the insulin­­incretin axis, autoimmune destruction of β­cells of the pancreas, etc. were highlighted in detail. The role of genetic factors in the development of diabetes against the background of acute pancreatitis is described. Currently there are no standardized unified criteria of type 3c diabetes, thus the main and additional diagnostic criteria according to the different authors have been analyzed in detail. The differential characteristics and features of the diagnosis of diabetes mellitus by type and peculiarities of the diagnosis of type 1, 2 and 3c diabetes mellitus have been presented. The discussion on the glycemic target goals for patients with type 3c diabetes and the need for screening and prevention of carbohydrate metabolism disorders in patients with acute pancreatitis has been outlined. The authors provided current recommendations for the treatment of type 3c diabetes and discussed the possibilities of the use of insulin in the basis/bolus mode to achieve compensation of carbohydrate metabolism. The necessity to compensate pancreas exocrine insufficiency to improve the assimilation of fats and fat‑soluble vitamins has been emphasized.

6688 Clinical Presentation and Management of Highly Differentiated Follicular Carcinoma Arising from Struma Ovarii with DICER1 Mutation: A Case Report

Abstract Disclosure: S.M. Seav: None. J. Shah: None. C. Dosiou: None. Background: Struma ovarii (SO) is a rare type of ovarian teratoma comprised of > 50% thyroid tissue. Extra-ovarian spread of SO, called peritoneal strumosis, was previously considered benign given the lack of histological malignant features. The 2020 WHO Classification of Female Genital Tumors has reclassified this as highly differentiated follicular carcinoma arising from struma ovarii (HDFCO), highlighting its low-grade malignant potential.[1] We report a case of HDFCO with extensive peritoneal disease and discuss its management. Clinical Case: A 38-year-old female presented to her OBGYN for irregular menses. Pelvic MRI showed an 8 cm right ovarian mass. Right salpingo-oopherectomy and pelvic peritoneal biopsies revealed well-differentiated thyroid tissue. Thyroid ultrasound demonstrated a multinodular goiter with ATA high risk nodules; 4 of 5 biopsied with benign results. Her thyroglobulin (Tg) was 170 ng/mL (normal 2 – 35 ng/ml). No further intervention was recommended. Two years later she was referred to our clinic. CT of abdomen/pelvis showed multifocal residual disease. We recommended more aggressive management, given the diagnosis of HDFCO. All visible disease was resected in a diagnostic laparoscopy with pelvic and omental biopsies. Pathology showed well-differentiated thyroid tissue. Molecular testing for the FGFR4 mutation associated with HDFCO was negative, but there was a DICER1 mutation c.5428 G>T of undetermined significance. DICER1 mutations are associated with thyroid cancers2. A total thyroidectomy and radioactive iodine ablation (RAI) were recommended. Thyroid pathology was benign. Tg was 9 ng/mL one month post-op. MRI six months post-laparoscopy revealed only one 6 mm omental lesion. Withdrawal I-123 whole body scan (WBS) showed multiple peritoneal implants. Tg was 214 ng/mL and TSH was 72 ulU/mL. The patient was treated with 157 mCi of oral I-131. Given the extensive peritoneal disease, she received prophylactic oral dexamethasone for 2 weeks after RAI to decrease the risk of peritoneal inflammation and bowel obstruction potentially mediated by local inflammation from radiation-related tissue injury. Her Tg three months post-RAI was 4 ng/mL. The surveillance plan is to alternate between RAI WBS and MRI abdomen/pelvis every 6 months. Conclusions: Peritoneal strumosis, previously considered benign, has recently been reclassified as HFDCO, an extremely rare low-grade malignancy with no standardized treatment. We report the first case of extensive HFDCO with a DICER1 mutation. Given the significant peritoneal involvement, our case was treated with total thyroidectomy, surgical excision of all implants, RAI, and prophylactic steroids post-RAI. Further research into the prognostic factors and optimal treatment of HFDCO is needed. Reference: [1]Giovanopoulou et al. Curr Oncol. 2022; 29(12): 9105-9116. 2Sauer et al. Head Neck Pathol. 2022; 16(1): 190–199. Presentation: 6/1/2024

7817 A Rare Case of Intrathyroidal Thyroglossal Duct Cyst Presenting as a Rapidly Expanding Left Thyroid Goiter

Abstract Disclosure: C.M. Godar: None. A.J. Spiro: None. K.F. Brown: None. M.K. Shakir: None. T.D. Hoang: None. Introduction: Thyroglossal duct cysts are the most common congenital cyst in the head and neck, found during childhood as a midline neck mass. We present a rare case of a large intrathyroidal thyroglossal duct cyst with left lateral extension in an adult patient. Case Report: A 50-year-old man with family history of familial adenomatous polyposis presented for thyroid nodule evaluation. Thyroid ultrasound for screening of thyroid cancer showed a 4.8 x 4.5 x 2.5cm mixed cystic/solid hyperechoic thyroid nodule with smooth margins in the left lower thyroid lobe. He reported no compressive symptoms. FNA with standard 27G needle was insufficient for evaluation with Bethesda I result. Attempted syringe aspiration did not produce cystic fluid for analysis. The patient returned to clinic 8 weeks later due to visible enlargement of his anterior neck and new neck pressure with swallowing. Physical exam was significant for a new, firm palpable mass over the left thyroid isthmus. Bedside ultrasound noted expansion of the previously visualized mass now extending into the thyroid isthmus. FNA was reattempted with a 25G needle, and cytologic material was again inadequate. He elected to undergo left hemithyroidectomy. Histologic sections demonstrated a 3.4cm simple squamous, non-keratinizing cyst lining overlying a thickened fibrotic wall with mixed acute and chronic inflammation surrounded by benign thyroid tissue, consistent with an intrathyroidal thyroglossal duct cyst. Discussion: The thyroglossal duct derives from epithelial tissue during embryogenesis and atrophies during weeks 8-10 of gestation. A persistent duct may lead to cyst formation in the presence of remnant epithelial tissue secretions and local neck inflammation. A thyroglossal duct cyst is usually located midline in the anterior neck. This stands in comparison to a branchial cleft cyst, which arises due to failure of atrophy of the second branchial groove during embryogenesis and forms a cyst that is usually located in the upper lateral neck compartment. Other common neck masses include lipomas, dermoid cysts, or ectopic thyroid tissue. This case highlights the rarity of intrathyroidal thyroglossal duct cyst in an adult patient and the importance of definitive diagnosis and appropriate management. Presentation: 6/2/2024

Perivascular Adipose Tissue Becomes Pro-Contractile and Remodels in an IL10-/- Colitis Model of Inflammatory Bowel Disease.

Inflammatory Bowel Diseases (IBDs) are associated with aberrant immune function, widespread inflammation, and altered intestinal blood flow. Perivascular adipose tissue (PVAT) surrounding the mesenteric vasculature can modulate vascular function and control the local immune cell population, but its structure and function have never been investigated in IBD. We used an IL10-/- mouse model of colitis that shares features with human IBD to test the hypothesis that IBD is associated with (1) impaired ability of PVAT to dilate mesenteric arteries and (2) changes in PVAT resident adipocyte and immune cell populations. Pressure myography and electrical field stimulation of isolated mesenteric arteries show that PVAT not only loses its anti-contractile effect but becomes pro-contractile in IBD. Quantitative immunohistochemistry and confocal imaging studies found significant adipocyte hyperplasia and increased PVAT leukocytes, particularly macrophages, in IBD. PCR arrays suggest that these changes occur alongside the altered cytokine and chemokine gene expression associated with altered NF-κB signaling. Collectively, these results show that the accumulation of macrophages in PVAT during IBD pathogenesis may lead to local inflammation, which ultimately contributes to increased arterial constriction and decreased intestinal blood flow with IBD.

8110 Lymphocytic Hypophysitis secondary to a ruptured Rathke’s Cleft Cyst complicated by post surgical recurrence: A rare phenomenon

Abstract Disclosure: M.S. Maharaul: None. F. Thelmo: None. I. Ahmed: None. Introduction: Lymphocytic hypophysitis secondary to ruptured Rathke’s cleft cyst (RCC) is a rare entity. Rathke’s cleft cysts are benign fluid-filled intra-sellar cysts that originate from the remnants of Rathke’s pouch and contain mucoid material. Most are asymptomatic; some may get symptomatic during cyst expansion and rupture releasing liquid content and trigger local inflammation. Surgical resection followed by glucocorticoids is usually curative. Case: A 42-year-old female presented to the hospital with one week history of right sided frontal headache associated with blurred vision in right eye. MRI Brain showed a 15 mm complex cystic lesion in the sella with suprasellar extension associated with peripheral calcifications. On admission, endocrine laboratory investigations including pregnancy test were normal. Ophthalmic testing did not reveal any acute abnormalities. Transsphenoidal surgery was performed for tumor resection. Pathology examination revealed infiltration of massive lymphocytes, macrophages, plasma cells, and eosinophils that were diagnostic of lymphocytic hypophysitis in the anterior pituitary lobe. She was started on glucocorticoids and discharged home. Rheumatology and Infectious diseases workup were unrevealing. On follow up 3 weeks later, she had self-discontinued steroids. The following week, she presented to the emergency room again with a right sided headache and blurred vision. MRI Brain revealed a 16 mm recurrent inflammatory mass lesion in the sella. Endocrine panel demonstrated an 8 am serum cortisol level of 7.4 mcg/dl, ACTH 20 pg/ml, FSH 6.2 mIU/ml, LH 4.9 mIU/ml, free T4 1.1 ng/dl and prolactin 8 ng/ml. She underwent transsphenoidal resection of the mass again and was restarted on glucocorticoids. This time pathology examination revealed an epithelial lined cyst most compatible with Rathke’s cleft cyst. She continued to remain on a glucocorticoid taper during the follow up period. On re-evaluation, her endocrinology laboratory investigations continued to show a deficiency of gonadotropins for which she is following up with OBGYN, but the remaining pituitary hormones were all within normal limits. Conclusion: Rathke’s Cleft Cysts (RCCs) should be in the differential diagnoses for evaluation of hypophysitis. There have only been a handful of cases in the literature of hypophysitis associated with a ruptured RCC, and only one case of recurrence after surgical debulking. This case provides an insight into the clinical behavior, diagnosis, and timely management of lymphocytic hypophysitis due to a ruptured Rathke’s cleft cyst and management post-recurrence. Presentation: 6/3/2024

Comprehensive comorbidity assessment for the ECOPD: a long-term multi-centre retrospective study

BackgroundExacerbation of chronic obstructive pulmonary disease (ECOPD) results in severe adverse outcomes and mortality. It is often associated with increased local and systemic inflammation. However, individual susceptibility to exacerbations remains largely unknown. Our study aimed to investigate the association between comorbidities and exacerbation outcomes.MethodsWe included patients with the primary discharge diagnosis of exacerbation for more 10 years in China. Data on all comorbidities were collected and analysed to determine the impact of the comorbidities on 1-year exacerbation readmission, length of hospital stay, and hospital cost. Univariable and multivariable logistic regression analyses were performed, and predictive models were developed.ResultsThis extensive investigation evaluated a total of 15,708 individuals from five prominent locations in China, revealing notable variations in the prevalence of comorbidities and healthcare expenses among different regions. The study shows that there is a high rate of readmission within one year, namely 15.8%. The most common conditions among readmitted patients are hypertension (38.6%), ischemic heart disease (16.9%), and diabetes mellitus (16.6%). An extensive multivariable study revealed that age, gender, and particular comorbidities such as malnutrition and hyperlipidemia are important factors that can significantly predict greater readmission rates, longer hospital stays or increased healthcare costs. The multivariable models show a moderate to good ability to predict patient outcomes, with concordance index ranging from 0.701 to 0.752. This suggests that targeted interventions in these areas could improve patient outcomes and make better use of healthcare resources.ConclusionsThe results regarding the association between severe exacerbations and systemic disease status support the integration of systematic evaluation of comorbidities into the management of exacerbations and the intensification of treatment of important comorbidities as a appropriate measure for prevention of further exacerbations. Our models also provide a novel tool for clinicians to determine the risk of the 1-year recurrence of severe ECOPD in hospitalised patients.

Management of dermatosis papulosa nigra: a systematic review.

Dermatosis papulosa nigra (DPN) is a variant of seborrheic keratosis that typically presents as hyperpigmented pedunculated papules on the face, trunk, and/or back in those with skin of color. Although benign, the lesions can cause significant discomfort and distress. Management options are limited and often unaffordable, as treatment is elective in most cases. This study was undertaken to provide an updated summary of safe and efficacious treatments for DPN. Five databases were searched to identify full-text publications reporting on treatments and outcomes in adults with DPN. Seventeen publications met inclusion criteria and were included: six cohort studies, one randomized controlled trial, five case report studies, one case series, and four pilot studies. Treatment options included simple excision, curettage, electrodesiccation, cryotherapy, topicals, and laser therapies. These modalities varied in their documented outcomes and associated potential adverse effect profiles. Postinflammatory hyperpigmentation is a common adverse effect that often leads to patient dissatisfaction. It can be mitigated with topical treatments aimed at reducing local inflammation. Study limitations included small sample size in individual studies, lack of consistent reporting of Fitzpatrick skin type, and lack of comparison to the standard treatment of electrodesiccation or curettage. Ultimately, treatment should consider the patient's Fitzpatrick type, treatment area, associated costs, and potential adverse effects.

Skin organoid transplantation promotes tissue repair with scarless in frostbite.

Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells and fibroblasts during frostbite. Most importantly, human-induced pluripotent stem cell (hiPSC) -derived skin organoids combining with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment significantly accelerated wound healing by reducing early inflammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fibroblasts, significantly reduced fibroblast-to-myofibroblast transition by regulating the integrin α5β1-FAK pathway, and remodeled the extracellular matrix (ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfigurement and skin dysfunction caused by frostbite.

Ovarian Puncture Triggers an Inflammatory Response that did not Affect Late Folliculogenesis, Ovulation Rate, and Fertility.

Ovarian puncture has been widely used in assisted reproduction, but there are still gaps about its effects on ovarian morphophysiology, as well as the relationship between inflammation caused by this procedure and the follicular growth and fertility. The aim of this study was to investigate the effects of ovarian puncture on folliculogenesis and fertility. Mice (n = 24) were divided into two groups: (1) SHAM-both ovaries were exposed and repositioned and (2) Punctured-ovaries were exposed, punctured, and repositioned. After 96h of surgery, ovaries were collected for morphofunctional analysis. New females were used for the superovulation (n = 10) and fertility assays (n = 10). Increased volumetric density of inflammatory cells-p = 0.0005, p = 0.0013; hemorrhagic foci-p < 0.0001; and inflammatory exudate-p < 0.0001 could be noticed on the punctured group, compared to SHAM. The percentage of primordial follicles was lower on the punctured ovaries (p = 0.00294). Ovarian puncture has also induced an increase in the proliferation of granulosa cells of primary (p = 0.0321) and antral follicles (p = 0.0395), and an increased apoptotic index of antral follicles (p = 0.0100). There was no influence on expression of some genes related to inflammation, collagen deposition and folliculogenesis progression. The reproductive aspects (oocyte retrieval and number of fetuses per female) were not altered (p > 0.05). Taken together, our findings strongly suggest that ovarian puncture results in a local inflammation that affects follicular growth and atresia. However, it does not affect female fertility, which strengthens the safety of this procedure.

Algorithms for evaluation of minimal cut sets

Objective:We propose a way to enhance the evaluation of minimal cut sets (MCSs) in biological systems modeled by Petri nets, by providing criteria and methodology for determining their optimality in disabling specific processes without affecting critical system components. Methods:This study concerns Petri nets to model biological systems and utilizes two primary approaches for MCS evaluation. First is the analyzing impact on t-invariants to identify structural dependencies. Second is assessing the impact on potentially starved transitions caused by the inactivity of specific MCSs. This approach deal with net dynamics. These methodologies aim to offer practical tools for assessing the quality and effectiveness of MCSs. Results:The proposed methodologies were applied to two case studies. In the first case, a cholesterol metabolism network was analyzed to investigate how local inflammation and oxidative stress, in conjunction with cholesterol imbalances, influence the progression of atherosclerosis. The MCSs were ranked, with the top sets presented, focusing on those that disabled the fewest number of t-invariants. In the second case, a carbohydrate metabolism disorder model was examined to understand its impact on atherosclerosis progression. The analysis aimed to identify MCSs that could inhibit the atherosclerosis process by targeting specific transitions. Both studies utilized the Holmes software for calculations, demonstrating the effectiveness of the proposed evaluation methodologies in ranking MCSs for practical biological applications. Conclusion:The algorithms proposed in this paper offer an analytical approach for evaluating the quality of MCSs in biological systems. By providing criteria for MCS optimality, these approaches have potential to enhance the utility of MCS analysis in systems biology, aiding in the understanding and manipulation of complex biological networks.Algorithm are implemented within Holmes software, an open-source project available at https://github.com/bszawulak/HolmesPN.

A new nano approach to prevent tumor growth in the local treatment of glioblastoma: Temozolomide and rutin-loaded hybrid layered composite nanofiber

Total resection of glioblastoma (GB) tumors is nearly impossible, and systemic administration of temozolomide (TMZ) is often inadequate. This study presents a hybrid layered composite nanofiber mesh (LHN) designed for localized treatment in GB tumor bed. The LHN, consisting of polyvinyl alcohol and core-shell polylactic acid layers, was loaded with TMZ and rutin. In vitro analysis revealed that LHN™Z and LHNrutin decelerated epithelial-mesenchymal transition and growth of stem-like cells, while the combination, LHN™Z+rutin, significantly reduced sphere size compared to untreated and LHN™Z-treated cells (P < 0.0001). In an orthotopic C6-induced GB rat model, LHN™Z+rutin therapy demonstrated a more pronounced tumor-reducing effect than LHN™Z alone. Tumor volume, assessed by magnetic resonance imaging, was significantly reduced in LHN™Z+rutin-treated rats compared to untreated controls. Structural changes in tumor mitochondria, reduced membrane potential, and decreased PARP expression indicated the activation of apoptotic pathways in tumor cells, which was further confirmed by a reduction in PHH3, indicating decreased mitotic activity of tumor cells. Additionally, the local application of LHNs in the GB model mitigated aggressive tumor features without causing local tissue inflammation or adverse systemic effects. This was evidenced by a decrease in the angiogenesis marker CD31, the absence of inflammation or necrosis in H&E staining of the cerebellum, increased production of IFN-γ, decreased levels of interleukin (IL)-4 in splenic T cells, and lower serum AST levels. Our findings collectively indicate that LHN™Z+rutin is a promising biocompatible model for the local treatment of GB.

Recombinant Keratin-Chitosan Cryogel Decorated with Gallic Acid-Reduced Silver Nanoparticles for Wound Healing.

Wound healing is a complex physiological process that can be roughly divided into four stages: hemostasis, inflammation, proliferation, and remodeling. Conventional wound dressings often fail to meet the diverse needs of these healing stages due to their limited functionality. Cryogels, however, possess several attractive properties, such as large, interconnected pores, good mechanical strength, and ease of modification, making them suitable for developing advanced dressings with multiple functions. In this study, we developed a multifunctional cryogel dressing, with biocompatible polysaccharides as the main component, designed to provide a breathable, moist, and antibacterial microenvironment for chronic infected wounds, thereby promoting wound healing. Recombinant keratin 31 (RK31) was combined with chitosan (CS) to produce a CS/RK31 cryogel, referred to as CK. Gallic acid-reduced silver nanoparticles (GA/Ag NPs) were incorporated as the active antibacterial component to create the CS/K31@GA/Ag cryogel, known as CKGA. The cryogel was characterized using scanning electron microscopy (SEM) and a universal testing machine, and its biocompatibility was assessed in vitro. The dynamic hemostatic performance of the cryogel was evaluated with a rat tail amputation bleeding model. Additionally, the antibacterial effects of the cryogel against Staphylococcus aureus and Escherichia coli were tested using agar diffusion assays and turbidimetry. The antioxidant capacity of the CKGA cryogel was also measured in vitro. Finally, the cryogel's ability to promote wound healing was tested in an SD rat model of infected wounds. Characterization results showed that the CKGA cryogel features an interpenetrating porous network structure and exhibits excellent mechanical properties, with a swelling rate of up to 1800%. Both in vitro and in vivo experiments confirmed that the cryogel has good biocompatibility, effectively absorbs exudates, and rapidly stops bleeding. The addition of GA/Ag NPs provided significant antibacterial effects, achieving an inhibition rate of over 99.9% against both S. aureus and E. coli. Furthermore, CKGA cryogels demonstrated a strong scavenging capacity for ROS in a dose-dependent manner. Studies using the SD rat infected wound model showed that the cryogel effectively inhibited bacterial proliferation on wound surfaces, reduced local tissue inflammation, and promoted the healing of infected wounds. The multifunctional cryogel, with its rapid hemostatic, antibacterial, and antioxidant properties, as well as its ability to promote cell proliferation, could be widely used as a wound dressing for the healing of bacterial infections.

A short duration of mechanical ventilation alters redox status in the diaphragm and aggravates inflammation in septic mice

BackgroundMechanical ventilation (MV) is a life support method used to treat patients with respiratory failure. High tidal volumes during MV can cause ventilator-induced lung injury (VILI), but also affect other organs, such as the diaphragm (Dia) causing ventilator-induced diaphragmatic dysfunction (VIDD). VIDD is often associated with a complicated course on MV. Sepsis can induce inflammation and oxidative stress, contributing to the impairment of the Dia and worsening of the prognosis. This study evaluated the additive or synergistic effects of a short course of mechanical ventilation on Dia in healthy and septic adult mice. Methods32 adult male C57BL/6 mice were randomly into four groups: Control (CG), non-ventilated animals instilled with saline solution (PBS1x); Lipopolysaccharide (LPS), non-ventilated animals instilled with PBS solution containing lipopolysaccharide; Mechanical Ventilation (MV) for 1 h, ventilated animals instilled with PBS solution; and Mechanical Ventilation and LPS (MV+LPS), ventilated animals instilled with PBS solution containing LPS. At the end of the experimental protocol, the animals were euthanized, then blood and diaphragm tissue samples were collected. ResultsEvaluation of leukocyte/blood parameters and diaphragm muscle showed that MV, LPS and the combination of both were able to increase neutrophil count, creatine kinase, inflammatory mediators and oxidative stress in all groups compared to the control. MV and sepsis combined had additive effects on inflammation and lipid peroxidation. ConclusionsA short course of Mechanical ventilation promotes inflammation and oxidative stress and, its combination with sepsis further increases local and systemic inflammation.

Application of a modified multifunctional short peptide in the treatment of periodontitis

Periodontitis is a chronic inflammatory disease involving plaque biofilm as a pathogenic factor. Potassium ion plays an important role in cellular homeostasis; a large outflow of potassium may lead to local inflammation progression. In this work, the multifunctional short peptide molecule BmKTX-33 was designed by modifying the BmKTX, a Kv1.3 potassium channel inhibitor. This was to explore its antibacterial properties, capability of maintaining cell ion homeostasis, and bone-forming capacity. The results showed that BmKTX-33 had inhibitory effects on S. gordonii, F. nucleatum, and P. gingivalis. Moreover, BmKTX-33 also inhibited excessive potassium outflow in inflammatory environments. Finally, BmKTX-33 promoted MC3T3-E1 early osteogenesis while suppressing the NLRP3 inflammasome's production. In conclusion, BmKTX-33 not only has antibacterial properties, but also can inhibit the expression of NLRP3 inflammasome and play an anti-inflammatory role.

In vitro bio-activity of Rosa rubiginosa L. (sweet briar) rosehip fixed oil combined with essential oils for acne vulgaris

Cutibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus proliferate within accumulated sebum and produce localised inflammation thereby inducing acne vulgaris. Essential oils are one of the leading natural products used for acne and are diluted in fixed oils to reduce irritation and toxicity. This study investigated the in vitro antimicrobial, anti-inflammatory, cytotoxicity, and skin retention properties of Rosa rubiginosa rosehip fixed oil in combination with essential oils having activity against acne vulgaris. The broth microdilution assay was used to determine the minimum inhibitory concentration (MIC), and the sum of the fractional inhibitory concentration index (ΣFIC) was calculated for the interactions. The lipopolysaccharide (LPS) induced inflammatory pathway in RAW 264.7 macrophages was used to assess anti-inflammatory activity. A dual-staining method in A549 epithelial cells was used to assess cytotoxicity. Qualitative Fourier Transform Infrared spectroscopy analysis was used for initial skin retention determination. Rosa rubiginosa oil combined with Cinnamomum zeylanicum essential oil displayed antimicrobial synergy (MIC = 0.42 mg/ mL; ΣFIC = 0.45) against three acne-inducing strains. Rosa rubiginosa fixed oil combined with Styrax benzoin essential oil suppressed LPS-induced nitrite production by 33.80%. Rosa rubiginosa oil combined with Melaleuca quinquenervia essential oil exhibited the lowest cytotoxicity (84.32% cell viability). Rosa rubiginosa oil combined with either C. zeylanicum, Eugenia caryophyllata, Rosa damascena or S. benzoin essential oil was retained within the porcine skin. Rosa rubiginosa fixed oil serves as an ideal carrier oil that can potentiate selected essential oils for the treatment of acne vulgaris.

Recent advances in understanding the roles of T cells in atrial fibrillation

Atrial fibrillation (AF) is a common arrhythmia associated with severe outcomes like heart failure and stroke. Recent studies highlight the crucial role of T in AF. Clinical studies have observed elevated levels of CD4+CD28null T cells, Th17/Treg cells, CD8+ cells, and related markers in the peripheral blood or atrial tissue of AF patients, correlating with disease severity and cardiovascular events. These T cell subsets contribute to AF through: (1) releasing inflammatory factors like TNF-α and IL-17 which affect calcium homeostasis and electrical activity in atrial myocytes and/or promote atrial fibrosis; (2) recruiting inflammatory cells such as macrophages, causing local inflammation, oxidative stress, and atrial remodeling; (3) secreting cytotoxic proteins like perforin and granzymes, inducing apoptosis in atrial myocytes and affecting their action potentials; (4) direct contact, influencing atrial myocyte electrophysiology. Understanding these T cell-mediated mechanisms may uncover new therapeutic targets for AF.