Lower TNF-α Research Articles

Therapeutic implications of baricitinib in mouse model of vitiligo.

Vitiligo, an autoimmune disorder marked by skin depigmentation, is closely linked to immune dysregulation, including T cell infiltration and pro-inflammatory cytokines. This study explores the potential of baricitinib, a JAK-STAT inhibitor, in promoting repigmentation in vitiligo lesions by modulating immune responses. Using a mouse model of vitiligo induced by hydroquinone, we assessed the effects of baricitinib treatment on lesion repigmentation, CD8 + T cell infiltration, T cell populations, and serum TNF-α levels. Immunostaining, flow cytometry, and ELISA were used to analyse these parameters. Baricitinib treatment significantly reduced CD8 + T cell infiltration in the skin, lowered serum TNF-α levels, and decreased both CD4 + and CD8 + T cell populations in the blood. Remarkably, these immune modulations correlated with notable repigmentation of the lesions. Baricitinib effectively reduces inflammation and T cell infiltration, suggesting it as a promising therapeutic for vitiligo. These findings highlight its potential to modulate immune responses and restore skin pigmentation in vitiligo patients.

Trace Element Chromium-D-Phenylalanine Complex: Anti-Inflammatory and Antioxidant Insights from In Vivo and In Silico Studies.

The biological significance of trace elements such as chromium extends beyond basic cellular functions, influencing key processes like inflammation and oxidative stress. In this study, we explore the anti-inflammatory and antioxidant potential of a trace element complex, Chromium-D-phenylalanine (Cr(D-Phe)₃), through in vivo and in silico approaches. Anti-inflammatory activity was assessed using a carrageenan-induced paw oedema model in rats, coupled with histopathological and biochemical analyses. The antioxidant effects of Cr(D-Phe)₃ were evaluated by measuring reduced glutathione (GSH), lipid peroxidation (LPO), and tumour necrosis factor-alpha (TNF-α) as a marker of inflammation. Furthermore, molecular docking and dynamics simulations were conducted to elucidate the compound's binding affinity and stability with cyclooxygenase enzymes. Cr(D-Phe)₃ exhibited significant anti-inflammatory activity, with the 40μg/kg dose achieving 34.40% (p < 0.001) oedema inhibition, comparable to diclofenac sodium (42.40%). Treatment with Cr(D-Phe)₃ restored GSH levels (+ 62.10%, p < 0.001), reduced LPO (24.72%, p < 0.001), and lowered TNF-α (31.73%, p < 0.001) in carrageenan injected rats, demonstrating potent antioxidant and anti-inflammatory effects. Molecular docking revealed strong binding affinities between Cr(D-Phe)₃ and COX enzymes, suggesting its potential mechanism of action in modulating inflammatory pathways. This study highlights the potential of Cr(D-Phe)₃ as a chromium-based trace element complex with anti-inflammatory and antioxidant properties. These findings warrant further preclinical investigations to elucidate its full pharmacological potential and applications in managing inflammatory conditions.

The association between hair cortisol and burnout is moderated by age, psychosocial, and immunological markers

BackgroundExhaustion and depersonalization are the core symptoms of the occupational burnout. However, burnout is not an all-or-nothing phenomenon, but can occur in a milder to moderate form in otherwise healthy employees. In the last two decades hair cortisol concentrations (HCC) were increasingly related to the cumulative effect of psychosocial stress at work. We analyzed data of the Dortmund Vital Study (Clinicaltrials.gov: NCT05155397) to explore the relationship of HCC and burnout symptoms. Moreover, we asked whether the HCC – burnout association was moderated by work ability, chronic stress, neuroticism, depressive symptoms, and stress-related immunological biomarkers such as T cell concentration, CD4/CD8 cell ratio, and proinflammatory cytokines TNF- α, IL-6, and IL-18. MethodsBurnout was assessed by the Oldenburg Burnout Inventory (OLBI), and the Maslach Burnout Inventory (MBI) in 196 working adults aged between 20 and 65 years (mean age 42.2 years). Several self-reported variables and biomarkers were collected. ResultsThe results showed an association between HCC and the burnout measures. A series of moderator analyses revealed that the association between HCC and burnout symptoms was substantial for low work ability, high chronic stress level, high neuroticism level, and mild to moderate depressive symptoms. Immunological markers moderated the HCC – burnout association for high concentrations of T cells, low CD4/CD8 ratio and low IL-6, IL-18 and TNF-α concentrations. These interactions were moderated by age showing the largest impact in middle-aged to older individuals. ConclusionsThe present findings shed light on the complex interaction between burnout symptoms and work ability, chronic stress, personality, and the endocrinological and immunological responses across the working lifespan. These parameters should be considered when assessing the risk for developing burnout and validating the diagnosis of burnout. Trial RegistrationClinicalTrials.gov NCT05155397; https://clinicaltrials.gov/ct2/show/NCT05155397

Assessment of Lactobacillus acidophilus (L. acidophilus) therapeutic and prophylactic role in rats experimentally infected with Blastocystis subtype 3 (ST3).

Blastocystis, an eukaryote, inhabits the intestinal tract of humans and animals worldwide. Lactobacillus acidophilus (L. acidophilus), a probiotic, has been reported to be effective against blastocystosis. The present study evaluated the therapeutic and prophylactic effectiveness of L. acidophilus compared to metronidazole (MTZ) in rats experimentally infected with Blastocystis subtype 3 (ST3). Four groups of Blastocystis ST3-infected rats received MTZ, L. acidophilus, both MTZ and L. acidophilus, or prophylactic L. acidophilus. Non-infected and infected control groups were included. The effectiveness of treatment and prevention was evaluated using parasitological monitoring, histopathological examination, immunohistochemical staining for TNF-α and IgA expression, and immunological testing for TNF-α and IL-10. In the L. acidophilus-treated group, a 76% reduction in the mean fecal parasitic count and a 67% clearance in the intestinal wash were achieved aligning closely with outcomes observed in the MTZ-treated group. An immunomodulatory impact via upregulation of the anti-inflammatory cytokine IL-10 and downregulation of the pro-inflammatory cytokine TNF-α was demonstrated as well. Combined administration of MTZ and L. acidophilus exhibited superior efficacy with a 99% decrease in the mean fecal parasitic count and a 98% decrease in the intestinal fluid parasitic count. Additionally, the lowest TNF-α and the highest IL-10 serum levels. Prophylactic use of L. acidophilus for 7 days neither prevented infection nor reduced its severity. Furthermore, no significant differences were detected in serum levels of TNF-α and IL-10 following post-prophylaxis andpost-treatmentwith L. acidophilus. Accordingly, L. acidophilus might be recommended as an adjuvant treatment alongside MTZ for improved efficacy against blastocystosis.

Associations between serum cytokine levels and postmenopausal depression in postmenopausal women with and without menopause hormone therapy

BackgroundThe etiology of depression involves many biological and environmental factors, among which the inflammatory process is an important contributor. However, the role of pro-inflammatory cytokines in postmenopausal depression is unclear. Therefore, we aimed to explore the association between the serum concentrations of four pro-inflammatory cytokines (IL-1β, IL-6, IL-18, and TNF-α) and depressive symptoms in postmenopausal women who had been receiving menopause hormone therapy (MHT) for at least 6 months and postmenopausal women who had not received MHT.MethodsThis study included a total of 136 Chinese postmenopausal women aged 40 to 65 years who visited the gynecology outpatient department between June 2020 and December 2022. They were divided into the POST group (n = 94) and the POST + MHT (n = 42) group. Demographic information was collected, and the Hamilton Rating Scale for Depression (HAMD) was used to assess depression. The circulating levels of IL-1β, IL-6, IL-18, and TNF-α were determined using ELISA kits.ResultsAccording to the HAMD score, 39.36% of the participants in the POST group and 14.29% in the POST + MHT group were considered to have depression. The POST + MHT group had significantly lower serum concentrations of IL-18 and TNF-α than the POST group. Multiple linear regression analysis showed that the serum IL-18 (β = 3.996, 95% CI = 0.508–7.484), and TNF-α levels (β = 4.784, 95% CI = 0.939–8.629) were significant predictors of the HAMD-24 scores in women in the POST group. In addition, age was found to be positively related with the level of depression (β = 0.531, 95% CI = 0.063–0.999).ConclusionsPostmenopausal women who received MHT had a lower HAMD-24 score as well as lower serum TNF-α and IL-18 levels than women who did not receive MHT. Further, the TNF-α and IL-18 level were positively associated with the HAMD-24 score in women who had not received MHT.

Plasmatic Levels of Cytokines and Quality of Life among Elderly Individuals with Dizziness.

Introduction Few studies have investigated the relationship between cytokines and dizziness in elderly individuals. Objective To assess the levels of inflammatory biomarkers and their relationship with quality of life (QoL) among elderly individuals with dizziness. Methods We conducted a cross-sectional study with 103 participants (90 women and 13 men) who were assessed through the Visual Analogue Scale (VAS) and the Dizziness Handicap Inventory (DHI). The plasma levels of cytokines were measured through the cytometric bead array (CBA) method. Cross-tabulations with the Chi-squared test were used to verify sample homogeneity, and parametric tests were used to analyze the data. Results Out of the total sample of 103 individuals, dizziness was reported by 40 women and 5 men. A difference between the groups with and without dizziness was observed regarding the levels of interleukin 4 (IL-4; p = 0.011): the group without dizziness presented a higher mean level (2.1 ± 2.8 pg/mL) when compared to the group that presented dizziness (1.0 ± 1.7 pg/mL). Another difference was found between the DHI classifications and the plasma levels of tumor necrosis factor alpha (TNF-α;) p = 0.015): the groups without any losses in QoL presented lower TNF-α levels (1.4 pg/mL) compared to the group that presented moderate QoL loss (6.3 pg/mL). Conclusion Dizziness affects the functional, physical and emotional dimensions of QoL and plays a role in the decrease in the levels of IL-4 and in the presence of fullness and tinnitus. Higher VAS scores are related to dizziness in the elderly. Moreover, the increased levels of TNF-α were associated to light-to-moderate losses in QoL among elderly patients with dizziness.

Liver lipid metabolism, oxidative stress, and inflammation in glutamine-supplemented ob/ob mice.

Glutamine availability may be reduced in chronic diseases, such as type 2 diabetes mellitus (T2DM)-induced by obesity. Herein, the antioxidant, anti-inflammatory and lipid metabolism effects of chronic oral glutamine supplementation in its free and dipeptide form were assessed in ob/ob mice. Adult male C57BL/6J ob/ob mice were supplemented with L-alanyl-L-glutamine (DIP) or free L-glutamine (GLN) in the drinking water for 40 days, whilst C57BL/6J Wild-type lean (WT) and control ob/ob mice (CTRL) received fresh water only. Plasma and tissue (skeletal muscle and liver) glutamine levels, and insulin resistance parameters (e.g., GTT, ITT, insulin) were determined. Oxidative stress (e.g., GSH system, Nrf2 translocation), inflammatory (e.g., NFkB translocation, TNF-α gene expression) and lipid metabolism parameters (e.g., plasma and liver triglyceride levels, SRBP-1, FAS, ACC, and ChRBP gene expression) were also analyzed. CTRL ob/ob mice showed lower glutamine levels in plasma and tissue, as well as increased insulin resistance and fat in the liver. Conversely, chronic DIP supplementation restored glutamine levels in plasma and tissues, improved glucose homeostasis and reduced plasma and liver lipid levels. Also, Nrf2 restoration, reduced NFkB translocation, and lower TNF-α gene expression was observed in the DIP group. Interestingly, chronic free GLN only increased muscle glutamine stores but reduced overall insulin resistance, and attenuated plasma and liver lipid metabolic biomarkers. The results presented herein indicate that restoration of body glutamine levels reduces oxidative stress and inflammation in obese and T2DM ob/ob mice. This effect attenuated hepatic lipid metabolic changes observed in obesity.

The combination of microwave hyperthermia with TIPE2 impedes the growth of orthotopic colon cancer

Background Colon cancer (CC) is the main fatal disease of humans. Microwave hyperthermia (MH) is an adjuvant therapy for diverse cancers. Tumor necrosis factor-α induced protein-8-like 2 (TIPE2) is a tumor suppressor. However, the effect of MH combined with TIPE2 on CC remains unclear. Methods The orthotopic CC mouse model was constructed by mouse CC CT26-Luc cells, and mice were randomized into control, model (CT26-Luc), CT26-Luc + Vector, CT26-Luc + TIPE2, CT26-Luc + MH, and CT26-Luc + MH+TIPE2 groups (n = 6). Tumor growth pretreatment and post-treatment by in vivo fluorescence image analysis was detected. TIPE2 expression and cell transfection efficiency was detected by qRT-PCR and western blot. The pathological changes by HE staining, apoptosis by TUNEL staining, serum inflammatory factors by ELISA, TIPE2 expression by immunohistochemistry, and NF-κB signaling by western blot was performed. Results Paracancerous tissues showed higher TIPE2 expression than in CC tissues. CT26-Luc + TIPE2, CT26-Luc + MH, and CT26-Luc + MH+TIPE2 groups reduced tumor growth, tumor cell infiltration, and increased apoptosis. CT26-Luc + TIPE2 group had lower NF-κB, TNF-α, IL-1β, IL-6, p-p65, and p-IKK expression, and elevated TIPE2 and IkB expression, which was reversed by CT26-Luc + MH group. Moreover, CT26-Luc+MH+TIPE2 group showed opposite effects on the above factor expression of CT26-Luc+MH group. Conclusions Combination of MH with TIPE2 could impede CC tumor growth, providing scientific bases for its clinical application in CC treatment.

Influence of Biological Sex and Congenital Iron Deficiency on Neonatal Cytokine Responses.

Stimulated cord blood mononuclear cell (CBMC) cytokine responses were previously shown to predict the risk of childhood atopic disease. Iron deficiency (ID) at birth may also program atopic disease. Males are at a higher risk of pediatric atopic disease, but it is not known whether congenital ID impacts CBMC immune responses differentially by sex. Cord blood (CB) samples were collected from healthy term or near-term neonates after elective cesarean deliveries. A transferrin saturation ≤ 25% defined congenital ID. CBMCs were stimulated with either phytohemagglutinin (PHA) or PHA plus an iron chelator. Of the 85 neonates, the 26 neonates with congenital ID exhibited lower plasma tumor necrosis factor-α (TNF-α), as well as higher CBMC TNF-α and IL-8 responses than iron-sufficient neonates (p = 0.017, p = 0.013, and p = 0.007, respectively). Higher CBMC TNF-α responses were seen in both males and females with congenital ID. However, females with congenital ID also had lower plasma IL-6, lower plasma TNF-α, and higher CBMC interleukin (IL)-8 responses. Additionally, iron chelation during culture influenced stimulated CBMC IFN-γ and CBMC TNF-α responses. Congenital ID may influence stimulated CBMC cytokine responses, but results point to a sex-specific regulation of immune balance at birth. Because males are more prone to infantile ID and more likely to develop early childhood asthma, future studies should further investigate how fetal sex and congenital iron status impacts childhood immune responsiveness to infections and antigenic stimulation from the rearing environment.

Methyl-esterification, degree of polymerization and ∆4,5-unsaturation of galacturonic acid oligosaccharides as determinants of immunomodulation

In recent years, immunomodulation by pectin and pectin-derived galacturonic acid oligosaccharides has been the subject of wide-spread scientific research due to the potential of different pectin structures as bioactive biomolecules. Yet, gaps remain in understanding the structure-dependent immunomodulation of galacturonic acid. This study describes in vitro immunomodulatory effects of well-characterized galacturonic acid oligosaccharides. Both methyl-esterified and non-methyl-esterified galacturonic acid oligosaccharides with a saturated non-reducing end (degree of polymerization 1–10) significantly induced cytokine production by THP-1 macrophages and directly activated TLR2 and TLR4 in transfected HEK-293 cells, even when accounting for minor endotoxin contamination. In contrast, both methyl-esterified and non-methyl-esterified galacturonic acid oligosaccharides with a Δ4,5-unsaturated non-reducing end (degree of polymerization 1–7) did not activate TLR2 and TLR4 and led to significantly reduced cytokine production (p < 0.05), suggesting Δ4,5-(un)saturation as a pivotal factor for immunomodulation by galacturonic acid oligosaccharides. Exposure to non-methyl-esterified saturated galacturonic acid oligosaccharides resulted in significantly lower TNF-α production, IL-1β production and TLR4 activation (p < 0.05) compared to methyl-esterified saturated galacturonic acid oligosaccharides, while IL-10 production and TLR2 activation remained unchanged. These findings establish galacturonic acid oligosaccharides as versatile immunomodulators with TLR2 and TLR4 binding capacity, fit for different immunomodulatory applications depending on their structural characteristics.

Altered sleep and inflammation are related to outcomes in neonatal encephalopathy.

Immune dysregulation and delayed onset of sleep wake cycling (SWC) are associated with worse outcome in neonatal encephalopathy (NE), however the association between sleep and immune dysfunction in NE remains unclear. Aimed to evaluate association of sleep and systemic inflammation with outcomes in NE. Amplitude-integrated electroencephalography (aEEG) recordings were collected on infants undergoing therapeutic hypothermia (TH). Duration to onset of (SWC) and sleep quality (SQ) were examined. Blood samples collected during the first 2 days of life. Thirteen pro- and anti-inflammatory serum cytokines were quantified. Adverse outcome defined as death or abnormal MRI brain. Earlier onset of SWC and better SQ had less adverse outcomes. SQ provided better prognostic value and showed better interobserver agreement compared to duration to SWC. Better SQ associated with lower cytokines EPO and interleukin (IL)-1β. In infants with unfavourable outcome, shorter duration to SWC was associated with higher EPO and better SQ was associated with lower TNF-α. Earlier onset of SWC or better SQ showed less systemic inflammation and fewer adverse outcomes. SQ during TH provided better prognostic information than time of onset of SWC. Modulation of circadian rhythm in infants with NE may have an immunomodulatory role, leading to improved outcomes.

Assessing sepsis-induced immunosuppression to predict positive blood cultures.

Bacteremia is a life-threatening condition that can progress to sepsis and septic shock, leading to significant mortality in the emergency department (ED). The standard diagnostic method, blood culture, is time-consuming and prone to false positives and false negatives. Although not widely accepted, several clinical and artificial intelligence-based algorithms have been recently developed to predict bacteremia. However, these strategies require further identification of new variables to improve their diagnostic accuracy. This study proposes a novel strategy to predict positive blood cultures by assessing sepsis-induced immunosuppression status through endotoxin tolerance assessment. Optimal assay conditions have been explored and tested in sepsis-suspected patients meeting the Sepsis-3 criteria. Blood samples were collected at ED admission, and endotoxin (lipopolysaccharide, LPS) challenge was performed to evaluate the innate immune response through cytokine profiling. Clinical variables, immune cell population biomarkers, and cytokine levels (tumor necrosis factor [TNFα], IL-1β, IL-6, IL-8, and IL-10) were measured. Patients with positive blood cultures exhibited significantly lower TNFα production after LPS challenge than did those with negative blood cultures. The study also included a validation cohort to confirm that the response was consistent. The results of this study highlight the innate immune system immunosuppression state as a critical parameter for sepsis diagnosis. Notably, the present study identified a reduction in monocyte populations and specific cytokine profiles as potential predictive markers. This study showed that the LPS challenge can be used to effectively distinguish between patients with bloodstream infection leading to sepsis and those whose blood cultures are negative, providinga rapid and reliable diagnostic tool to predict positive blood cultures. The potential applicability of these findings could enhance clinical practice in terms of the accuracy and promptness of sepsis diagnosis in the ED, improving patient outcomes through timely and appropriate treatment.

Ex vivo-generated human CD1c+ regulatory B cells by a chemically defined system suppress immune responses and alleviate graft-versus-host disease

IL-10+ regulatory B cells (Bregs) show great promise in treating graft versus host disease (GVHD), a life-threatening complication of post-hematopoietic stem cell transplantation. However, obtaining high-quality human IL-10+ Bregs in vitro remains a challenge due to the lack of unique specific marker and the triggering of pro-inflammatory cytokines expression. Here, by uncovering the critical signaling pathways in Bregs induction by mesenchymal stromal cells (MSCs), we firstly established an efficient Bregs induction system based on MSCs and GSK-3β blockage (CHIR-99021), which had a robust capacity to induce IL-10+ Bregs while suppress TNF-α expression. Furthermore, these Bregs population could be identified and enriched by CD1c+. Mechanistically, MSCs induced the expansion of Bregs through the PKA-mediated phosphorylation of cAMP response element binding protein (CREB). Thus, we developed a chemical-defined inducing protocol by PKA-CREB agonist, instead of MSCs, which can also effectively induce CD1c+ Bregs with lower TNF-α expression. Importantly, induced CD1c+ Bregs suppressed the proliferation of PBMC and the inflammatory cytokines secretion of T cells. When adoptive transferred to a humanized mouse model of GVHD, induced CD1c+ Bregs effectively alleviated GVHD. Overall, we establish an efficient ex vivo induction system for human Bregs, which has implications in developing novel Bregs-based therapies for GVHD.

Association between olfactory function and metabolic syndrome in bipolar disorder patients: a cross-sectional study

BackgroundOlfactory function is closely related to mood and the endocrine system. However, the role of olfactory function in bipolar disorder combined with metabolic syndrome remains unclear. The purpose of this study was to explore the associations among olfactory function, tumor necrosis factor alpha (TNF-α), and metabolic syndrome and its components in patients with bipolar disorder.MethodsNinety-six bipolar disorder patients were divided into two groups with and without metabolic syndrome. We also included 46 healthy controls. Olfactory function was assessed using the Sniffin’ Sticks test. Blood samples were collected to measure metabolic indicators and serum TNF-α levels.ResultsSignificant differences in olfactory function were found among the three groups. Compared with the healthy controls, the bipolar disorder without metabolic syndrome group showed poorer olfactory identification ability (P < 0.001) and the bipolar disorder with metabolic syndrome group showed impaired olfactory sensitivity (P = 0.003) and olfactory identification (P < 0.001). Moreover, the bipolar disorder with metabolic syndrome group had poorer olfactory identification ability than the bipolar disorder without metabolic syndrome group (P = 0.015). Both bipolar disorder groups showed lower TNF-α levels than healthy controls. However, there was no significant difference between the two patient groups. Correlation analysis showed that, in the bipolar disorder with metabolic syndrome group, olfactory identification was negatively correlated with systolic blood pressure (r = − 0.424, P = 0.031), and serum TNF-α level was negatively correlated with body mass index (BMI; r = − 0.398, P = 0.049), triglyceride (r = − 0.503, P = 0.010), total cholesterol (r = − 0.491, P = 0.013), low-density lipoprotein-cholesterol (r = − 0.491, P = 0.013), and high-density lipoprotein-cholesterol (r = − 0.454, P = 0.023).ConclusionsThe olfactory identification ability of patients with bipolar disorder is worse than that of healthy controls, and the occurrence of metabolic syndrome will further aggravate the olfactory identification impairment of those patients. Furthermore, there may be a stronger link between serum TNF-α level and multiple metabolic indicators in bipolar disorder patients with metabolic syndrome than in bipolar disorder patients without metabolic syndrome.

Evaluating the Effect of Argon and Helium Atmospheric Cold Plasma Jets on Wound Healing in Rats: A Comparative Histopathological and Biochemical Analysis

Background: Cold atmospheric plasma (CAP) has emerged as a promising therapy for wound healing to deliver controlled doses of reactive species to tissues. Argon and helium, as gases used in CAP, are noted for their unique properties and therapeutic potential. Objectives: This study compared the effects of argon and helium atmospheric cold plasma jets on wound healing in a rat model, assessing histopathological changes and biochemical parameters. Methods: This randomized, controlled experimental study involved 18 male Wistar rats randomly assigned to control, helium-treated, and argon-treated groups. Wounds were created between the shoulders under anesthesia, treated with respective plasmas, and monitored for healing progress through macroscopic and microscopic evaluations. Results: Hemoglobin (HGB) and hematocrit (HCT) levels were significantly higher in experimental groups compared to controls (P &lt; 0.05), while mean corpuscular volume (MCV) was lower (P &lt; 0.05). Tumor necrosis factor alpha (TNF-α) levels were highest in helium-treated and lowest in argon-treated rats (P &lt; 0.05). Argon-treated rats showed enhanced IL-6, hyperemia, angiogenesis, and re-epithelialization, with lower TNF-α and necrotic layer thickness than other groups (P &lt; 0.05). Conclusions: Both argon and helium atmospheric cold plasma jets enhanced wound healing in rat models, demonstrating superior efficacy in promoting angiogenesis and re-epithelialization processes.

Evaluation of the Anti-Inflammatory/Immunomodulatory Effect of Teucrium montanum L. Extract in Collagen-Induced Arthritis in Rats.

The anti-inflammatory/immunomodulatory effects of Teucrium montanum L. (TM), a plant distributed in the Mediterranean region, have been insufficiently examined. The effects of the TM ethanol extract were tested in a rat collagen-induced arthritis (CIA) model of rheumatoid arthritis. LC-MS was used for the phytochemical analysis of the TM extract. Dark Agouti rats were immunized with bovine type II collagen (CII) in incomplete Freund's adjuvant for CIA, and treated with 100 or 200 mg/kg of TM extract daily via oral administration. Clinical and histopathological evaluations and a flow cytometric analysis of the phenotypic and functional characteristics of splenocytes and draining lymph node cells were performed. The cytokines in the paw tissue culture supernatants and anti-CII antibodies in serum were determined by ELISA. The TM extract, with the dominant components verbascoside and luteolin 7-O-rutinoside, reduced the arthritic score and ankle joint inflammation in CIA rats, promoted the antioxidant profile in serum, and lowered pro-inflammatory TNF-α, IL-6 and IL-1β production. It suppressed the activation status of CD11b+ cells by lowering CD86, MHCII and TLR-4 expression, and promoted the Th17/T regulatory cell (Tregs) balance towards Tregs. A lower frequency of B cells was accompanied by a lower level of anti-CII antibodies in treated rats. These findings imply the favorable effect of TM extract on the clinical presentation of CIA, suggesting its anti-inflammatory/immunomodulatory action and potential therapeutic effect.

Effect of Kangfuxin liquid combined with triamcinolone acetonide in oral submucosal fibrous degeneration

Purpose: To investigate the effect of Kangfuxin liquid combined with triamcinolone acetonide in the treatment of oral submucous fibrous degeneration. Methods: A total of 140 patients with oral submucosal fibrous degeneration admitted to the outpatient clinic of Haiyan County Stomatological Hospital, China from June 2020 to June 2023 were divided equally into study and control groups. The study group received Kangfuxin liquid in addition to 1 mL triamcinolone acetonide (40 mg/mL) while the control group received 1 mL triamcinolone acetonide; therapeutic effects were compared after 4 weeks of treatment. Visual analogue scale (VAS) score, serum transforming growth factor (TGF-β1), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were determined. Also, whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte sedimentation rate (ESR), and incidence of adverse reactions were evaluated. Result: The study group showed significantly reduced pain levels compared to the control group, as well as lower mucosal damage areas and improved mouth opening after 4 weeks of treatment compared to control group (p &lt; 0.05). Also, the study group showed significantly lower TGF-β1, TNF-α and IL-6 compared to control group after treatment (p &lt; 0.05). It showed significantly lower WBV, PV, and ESR compared to control group (p &lt; 0.05). Furthermore, the study group showed significantly lower incidence of adverse reactions than the control group (p &lt; 0.05). Conclusion: Kangfuxin liquid, when combined with triamcinolone acetonide, lowers pain, reduces the levels of STGF-β1, improves hemorheology, and produces minimal adverse effects compared to triamcinolone alone. Future studies should focus on long-term outcomes to better assess the therapeutic potential of this combined regimen.

Intratracheal Surfactant Administration Attenuates Hyperoxia-Induced Lung Injury and Fibrosis in Neonatal Rats

Abstract Background: Hyperoxia decreases surfactant production and suggests exogenous surfactant may be a potential treatment for hyperoxia-induced lung injury. This study aimed to investigate the effects of an animal-derived surfactant on hyperoxia-induced lung injury and fibrosis in newborn rats. Methods: Sprague Dawley rat pups were randomly reared either in room air (RA) or hyperoxic conditions (85% O2) from postnatal days 1–14. On postnatal day 4, the rats received an intratracheal injection of either 20 μL of normal saline (vehicle) or 20 μL of surfactant (Survanta). Our study included four study groups: RA + vehicle, RA + surfactant, 85% O2 + vehicle, and 85% O2 + surfactant. Body weights were recorded at birth and on postnatal days 4 and 14. On postnatal day 14, the lungs were dissected for histology, Western blotting, and cytokine measurements. Results: The hyperoxia-reared rats exhibited significantly higher lung injury scores, tumor necrosis factor-α (TNF-α) expression, transforming growth factor-β1 (TGF-β1) expression, and collagen deposition compared with the RA-reared rats. The surfactant alleviated hyperoxia-induced lung injury, inflammation, and fibrosis, as evidenced by the lower lung injury score, TNF-α expression, TGF-β1 expression, and collagen deposition in the lungs. Conclusion: The intratracheal administration of the surfactant ameliorated hyperoxia-induced lung injury and fibrosis and downregulated TNF-α and TGF-β1 expression, most likely by inhibiting lung inflammation and collagen deposition.

Enhanced clindamycin delivery using chitosan-coated niosomes to prevent Toxoplasma gondii strain VEG in pregnant mice: an experimental study

BackgroundCongenital toxoplasmosis occurs when a pregnant woman becomes infected with Toxoplasma gondii (T. gondii) for the first time. Treatment typically involves antimicrobial medications, with spiramycin commonly used to prevent transmission. However, spiramycin's effectiveness is limited due to poor placental penetration. Clindamycin, another antibiotic, can cross the placenta but reaches the fetus at only half the maternal concentration. Encapsulating the drug in chitosan-coated niosomes (Cs-Nio) could enhance its effectiveness by targeting specific organs and ensuring sustained release. To address the challenges of using clindamycin, a niosome-coated chitosan system was investigated for treating congenital toxoplasmosis caused by the VEG strain of T. gondii in an animal model.MethodsPregnant mice were infected with VEG strain of T. gondii on the 12th day of pregnancy, followed by treatment with various drugs across six groups. The treatments included chitosan-coated niosomes loaded clindamycin (Cs-Nio-Cli) and other controls. Parasitological evaluations (microscopic examination and real-time PCR), along with histopathological and immunological assessments were conducted to assess treatment efficacy. Finally, statistical analysis was conducted using GraphPad Prism 8.0 and SPSS 26, comparing test and control groups with T test and Mann–Whitney test. A p ≤ 0.05 was considered statistically significant.ResultsThe study found that treatment with Cs-Nio-Cli significantly reduced the number of T. gondii cysts in the brain and eyes (97.59% and 92.68%, respectively) compared to the negative control group. It also mitigated inflammatory changes, prevented cell death, and reduced vascular cuffs in the brain. In addition, Cs-Nio-Cli treatment decreased bleeding, placental thrombosis, and inflammatory cell infiltration in the placenta while improving eye tissue health by reducing retinal folds and bleeds. Immunologically, nanoclindamycin treatment resulted in lower TNF-α cytokine levels and higher IL-10 levels, indicating an enhanced anti-inflammatory response.ConclusionsAlthough Cs-Nio-Cli demonstrates promise in reducing the transmission of congenital toxoplasmosis and mitigating the effects of congenital toxoplasmosis, additional research is necessary to determine the optimal treatment regimens for the complete eradication of the parasite in the fetus.

Exploring the therapeutic applications of nano-therapy of encapsulated cisplatin and anthocyanin-loaded multiwalled carbon nanotubes coated with chitosan-conjugated folic acid in targeting breast and liver cancers

This study aimed to assess the targeted nano-therapy of encapsulated cisplatin (Cis) and anthocyanin (Ant)-loaded multiwalled carbon nanotubes (CNT) coated with chitosan conjugated folic acid on breast MCF7 and liver HepG2 cancer cells. Zeta potential, UV-spectroscopy, FTIR, TEM, and SEM were used to evaluate CNT, its modified form (CNT Mod), CNT-loaded Cis NPs, CNT-loaded Ant NPs, and CNT- Cis + Ant NPs. All treatments induced apoptosis-dependent cytotoxicity in both cell lines as revealed functionally by the MTT assay, morphologically (DNA degradation) by acridine orange/ethidium bromide (AO/EB) double staining, and molecularly (Bax upregulation and Bcl2 downregulation) by real-time PCR, with best effect for the combined treatment (CNT- Cis + Ant NPs). This combined treatment also significantly reduced inflammation (low TNFα), migration (low MMP9 and high TIMP1), and angiogenesis (low VEGF), while significantly increasing antioxidant status (high Nrf2 and OH-1) in MCF7 and HepG2 cells compared to other treatments. Interestingly, cells treated with CNT Mod exhibited higher cytotoxic, apoptotic, anti-migratory, and anti-angiogenic potentials relative to CNT-treated cells. In conclusion, targeted nano-therapy of encapsulated cisplatin and anthocyanin-loaded carbon nanotubes coated with chitosan conjugated folic acid can efficiently combat breast and liver cancers by sustained release, in addition to its apoptotic, antioxidant, anti-inflammatory, anti-metastatic, and anti-angiogenic effects.