Tissue Inflammatory Response Research Articles

Results of Controlled tissue regeneration in surgery for diabetic foot syndrome

Relevance. The problem of tissue regeneration in diabetic foot syndrome has currently become particularly relevant due to the multipolarity of the mechanisms of trophic disorders, their tendency to recur, the expansion of the affected areas when using traditional treatment methods, resistance to drug treatment methods, deterioration of patients' quality of life, as well as due to the significant expenditure of time and effort required for treatment. All these factors lead to significant economic costs in the management of patients in this cohort.The aim of the study: to develop new combined methods of surgical treatment of tissue defects in patients with complicated forms of diabetic foot syndrome.Materials and methods. The paper presents an original approach to solving one of the urgent problems of modern surgery of complications of diabetes mellitus, to the treatment of pathological processes of soft tissues of the lower extremities.Conclusions. At the stages of the entire study period, rapid wound healing was registered regardless of the initial clinical data and patient's medical history. There was also a decrease in the inflammatory response and active restoration of damaged tissues.

Xuetongsu ameliorates synovial inflammatory hyperplasia in rheumatoid arthritis by inhibiting JAK2/STAT3 and NF-κB signaling pathways

Ethnopharmacological relevanceSynovial inflammatory hyperplasia is the key pathological process that leads to further joint damage in rheumatoid arthritis (RA) progress. Kadsura heteroclita (Roxb) Craib, also called Xuetong in Chinese Tujia ethnomedicine, is utilized for its medicinal properties, including promoting blood circulation, dispelling “wind evil”, and relieving “damp evil”. It has been used in the treatment of arthralgia and RA, within Tujia ethnomedicinal practices. Xuetongsu (XTS), the main component of Xuetong, has been shown to inhibit the proliferation of RA fibroblast-like synovial cells (RAFLS) cells. However, the molecular mechanism of XTS in RA treatment requires further investigation. Aim of the studyTo observe the therapeutic effect of XTS on synovial inflammatory hyperplasia in rheumatoid arthritis, focusing on its underlying molecular mechanisms involving the janus kinase 2 (JAK2)/transducer/activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB) signaling pathways. Materials and methodsProtein-protein interaction (PPI) and molecular docking were used to find the main targets of XTS treatment for RA. In lipopolysaccharide (LPS)-induced RAFLS and RAW264.7 cells in vitro models, the levels of inflammatory cytokines were analyzed using enzyme linked immunosorbent assay (ELISA), and the expression of JAK2, STAT3, and NF-κB signaling pathways, as well as cyclooxygenase-2 (COX-2), were analyzed through western blotting test. A hemolysis assay was used to certify the biosecurity of XTS. A model of adjuvant arthritis (AIA) was established in 40 male rats, and different doses of XTS were administered, followed by an automatic blood routine, ELISA assay, hematoxylin and eosin (H&E) staining, and radiological analysis of the effect of no XTS on blood cytokines, histological changes, and improvement of posterior paw bone destruction in AIA rats. The protein levels of inflammatory cytokines were analyzed by immunofluorescence, immunohistochemistry, or Western blot. Finally, H&E staining was used to detect the damage of XTS on the heart, liver, spleen, lung, and kidney of AIA rats. ResultsOur results demonstrate that XTS effectively inhibited LPS-induced inflammatory responses in RAFLS and RAW264.7 cells by modulating the JAK2/STAT3 and NF-κB signaling pathways. Moreover, XTS administration in the AIA rats model significantly ameliorated paw swelling. Histological analysis revealed that XTS also suppressed the inflammatory response in paw tissue by modulating the JAK2/STAT3 and NF-κB signaling pathways. Importantly, during the treatment, XTS exhibited excellent safety profiles, as it did not induce any abnormalities in blood routine parameters or cause organ damage in the rats. ConclusionsOur findings highlight XTS as a promising natural agent for inhibiting synovial hyperplasia in RA. XTS holds great potential as an unprecedented natural agent for developing novel therapeutic strategies to target synovial hyperplasia in RA.

Oral manifestations of COVID-19 in children: a narrative literature review

COVID-19 triggers an acute inflammatory response in organs, tissues, tongue mucosa, and salivary glands. Some symptoms such as lesions on the tongue and oral mucosa, oral pseudomembranous candidiasis, pharyngitis, taste alteration, gingivitis, canker sores, and even multisystem inflammatory syndrome have been reported in children with COVID-19. Early diagnosis of oral manifestations improves patients' prognosis and quality of life. A narrative literature review was conducted based on studies published in PubMed and LiLacs from January 2020 to April 2024, related to oral manifestations in COVID-19 in children. Of the 68 articles found, 7 were selected after analysis. The main manifestations presented were: abscesses, mucositis, ulcerative lesions, gingivitis, pseudomembranous candidiasis, mucosal lesions, lip and tongue fissures, hemorrhagic crust, inflammation of salivary glands, lip swelling, and reactive infectious mucocutaneous eruption. The selected articles showed that these oral manifestations of COVID-19 can affect children in various age groups, serving as indicators of the disease and signs of worsening infection.

Development of Sensitive In Vitro Protocols for the Biocompatibility Testing of Medical Devices and Pharmaceuticals Intended for Contact with the Eyes: Acute Irritation and Phototoxicity Assessment.

This study introduces a novel in vitro methodology that employs the 3-D reconstructed tissue model, EpiOcular, to assess the irritation and phototoxicity potential of medical devices and drugs in contact with the eye. Our study evaluated diverse test materials, including medical devices, ophthalmological solutions and an experimental drug (cemtirestat), for their potential to cause eye irritation and phototoxicity. The protocols used in this study with the EpiOcular tissue model were akin to those used in the ultra-mildness testing of cosmetic formulations, which is challenging to predict with standard in vivo rabbit tests. To design these protocols, we leveraged experience gained from the validation project on the EpiDerm skin irritation test for medical devices (ISO 10993-23:2021) and the OECD TG 498 method for photo-irritation testing. The predictions were based on the tissue viability and inflammatory response, as determined by IL-1α release. By developing and evaluating these protocols for medical devices, we aimed to expand the applicability domain of the tests referred to in ISO 10993-23. This will contribute to the standardisation and cost-effective safety evaluation of ophthalmic products, while reducing reliance on animal testing in this field. The findings obtained from the EpiOcular model in the photo-irritation test could support its implementation in the testing strategies outlined in OECD TG 498.

Identification, genome-wide sequencing and analysis of drug resistance genes in a novel Vibrio harveyi strain isolated from yellowfin seabream

Yellowfin seabream (Acanthopagrus latus) is a fast-growing, adaptable species crucial for fish farming in southern China. However, as aquaculture of this species expands, diseases caused by bacteria, particularly Vibrio harveyi, are causing substantial economic losses. In this study, we isolated and identified a Vibrio harveyi strain denoted VH-AQ-SCAU-GZ23 from the diseased fish. Clinical signs of VH-AQ-SCAU-GZ23 infection were slow swimming, loss of appetite, loss of scales, severe liver congestion, and swelling of the gill filaments. VH-AQ-SCAU-GZ23 also induced an inflammatory response in yellowfin snapper spleen, liver, and brain tissue. To examine its pathogenicity and antibiotic susceptibility, we analyzed the genome sequence of this strain with third-generation high-throughput technology. The VH-AQ-SCAU-GZ23 genome was found to comprise a circular chromosome and three plasmids. Virulence factor analysis indicated that VH-AQ-SCAU-GZ23 contains a TLH gene encoding a thermolysin that increases virulence. Additionally, several antibiotic resistance genes were identified, including those encoding β-lactams, tetracyclines, aminoglycosides, quinolones, macrolides, peptides, and other antibiotics. To assess the drug sensitivity of those antibiotic resistance genes, we cloned ten resistance genes and transfected them into Escherichia coli DH5α for drug susceptibility testing. These resistance genes enhanced the resistance of DH5α to streptomycin, ampicillin, and penicillin G, among other antibiotics. Our study provides crucial support and a theoretical basis for advancing understanding of Vibrio harveyi. The insights gained are expected to provide guidance for future endeavors aimed at preventing and managing marine bacterial infections.

Neuroprotective effect of diosmin against chlorpyrifos-induced brain intoxication was mediated by regulating PPAR-γ and NF-κB/AP-1 signals

Chlorpyrifos (CPF) is a widely used organophosphate (OP) pesticide. Unfortunately, pesticides are known to cause neuronal intoxication. Diosmin (DS) is an antioxidant, anti-inflammatory, and neuroprotective flavonoid with high efficacy and safety. We plan to investigate the efficacy of DS in treating CPF-induced neurotoxicity, as well as the mechanisms underlying the protective effects. In our study, rats were randomized into 5 groups: control, DS (50 mg/kg), CPF (10 mg/kg), CPF + DS (25 mg/kg), and CPF + DS (50 mg/kg). The results indicated that DS ameliorated neuronal intoxication induced by CPF, evidenced by decreasing Tau, p-Tau, and β-amyloid. Histological examinations support these findings. DS significantly ameliorated CPF-induced neuronal oxidative injury by decreasing MDA content and elevating GSH, GST, and SOD levels mediated by PPAR-γ upregulation. DS suppressed CPF-induced brain inflammation by decreasing MPO enzymatic activity and TNF-α, IL-1β, and IL-6 levels mediated by downregulation of NF-κB/AP-1(c-FOS and c-JUN) signal. Of note, DS protective effects were dose dependent. In conclusion, our data suggested that DS was a promising therapeutic strategy for attenuating CPF-induced neuronal intoxication by restoring oxidant-antioxidant balance and inhibiting inflammatory response in brain tissues.

Cardiac Histopathology Alterations Induced by Subchronic Mangosteen Rind Extract in Wistar Rats

Mangosteen (Garcinia mangostana L.) is renowned for its potent antioxidant characteristics, including free radical scavenging, and its antibacterial, antifungal, anti-inflammatory, and antidiabetic properties. This study aims to assess the subchronic toxicity effects of ethanol extract from mangosteen rind on the cardiac histopathology of male and female Wistar rats. This research was a posttest-only control group design. Forty biological specimens from 40 Wistar rats were divided into four groups, a control group, and three treatment groups, which were given ethanol extract of mangosteen rind with doses of 250 mg/kg, 500 mg/kg, and 1,000 mg/kg for 28 days. Cardiac specimens were prepared and examined using hematoxylin-eosin (HE) staining at the Anatomical Pathology Laboratory of Universitas Jenderal Achmad Yani in December 2021. The findings indicated that prolonged ingestion of large amounts of ethanol extract from mangosteen rind can cause toxic effects characterized by an inflammatory response in cardiac tissue. No fibrosis or hypertrophy was detected; however, inflammatory changes such as the presence of inflammatory cells, vacuolar changes, and neovascularization were observed. The inflammation observed might be due to excessive antioxidant administration leading to oxidative stress. Inflammatory cells may trigger fibrotic remodeling in the heart. The difference in the quantity of inflammatory cells between male and female rats suggests that gender influences the inflammatory response. Overall, administration of ethanol extract from mangosteen rind at doses of 250 mg/kg, 500 mg/kg, and 1,000 mg/kg cause subchronic toxicity effects on the heart histopathology of Wistar rats, marked by inflammation.

Salidroside enhances NO bioavailability and modulates arginine metabolism to alleviate pulmonary arterial hypertension

BackgroundSalidroside (SAL), derived from Rhodiola, shows protective effects in pulmonary arterial hypertension (PAH) models, but its mechanisms are not fully elucidated.ObjectivesInvestigate the therapeutic effects and the mechanism of SAL on PAH.MethodsMonocrotaline was used to establish a PAH rat model. SAL’s impact on oxidative stress and inflammatory responses in lung tissues was analyzed using immunohistochemistry, ELISA, and Western blot. Untargeted metabolomics explored SAL’s metabolic regulatory mechanisms.ResultsSAL significantly reduced mean pulmonary artery pressure, right ventricular hypertrophy, collagen deposition, and fibrosis in the PAH rats. It enhanced antioxidant enzyme levels, reduced inflammatory cytokines, and improved NO bioavailability by upregulating endothelial nitric oxide synthase (eNOS), soluble guanylate cyclase (sGC), cyclic guanosine monophosphate (cGMP), and protein kinase G (PKG) and decreases the expression of endothelin-1 (ET-1). Metabolomics indicated SAL restored metabolic balance in PAH rats, particularly in arginine metabolism.ConclusionsSAL alleviates PAH by modulating arginine metabolism, enhancing NO synthesis, and improving pulmonary vascular remodeling.

Chronic ethanol exposure decreases H3K27me3 in the Il6 promoter region of macrophages and generates persistent dysfunction on neutrophils during fungal infection.

The aim of this study was to investigate the effects of ethanol exposure on epigenetic markers in bone marrow (BM) and their impact on inflammatory response during Aspergillus fumigatus infection. Chronic ethanol exposure decreased H3K27me3 enrichment in the Il6 promoter region while increased H3K4me3 enrichment in Tnf. Chimeric mice were generated by transplanting BM from mice exposed to ethanol or water. Infection of ethanol-chimeric mice culminated in higher clinical scores, although there was no effect on mortality. However, previous chronic exposure to ethanol affects persistently the inflammatory response in lung tissue, demonstrated by increased lung damage, neutrophil accumulation and IL-6, TNF and CXCL2 production in ethanol-chimeric mice, resulting in a decreased neutrophil infiltration into the alveolar space. Neutrophil killing and phagocytosis were also significantly lower. Moreover, BM derived macrophages (BMDM) from ethanol-chimeric mice stimulated with A. fumigatus conidia exhibited higher levels of TNF, CXCL2 and IL-6 release and a higher killing activity. The Il6 promoter of BMDM from ethanol-chimeric mice exhibited a reduction in H3K27me3 enrichment, a finding also observed in BM donors exposed to ethanol. These evidences demonstrate that prior chronic alcohol exposure of bone-marrow modify immune effector cells functions impairing the inflammatory response during A. fumigatus infection. These findings highlight the persistent impact of chronic ethanol exposure on infectious disease outcomes.

Cardiac alterations induced by Heloderma horridum horridum venom in rats: An experimental study with ECG analysis using a linear regression algorithm

Envenomation by reptile venom, particularly from lizards, poses significant health risks and can lead to physiological and cardiovascular changes. The venom of Heloderma horridum horridum, endemic to Colima, Mexico, was tested on Wistar rats. Electrocardiographic (ECG) data were collected pre-treatment and at 5-min intervals for 1 h post-envenomation. A specially designed computational linear regression algorithm (LRA) was used for the segmentation analysis of the ECG data to improve the detection of fiducial points (P, Q, R, S, and T) in ECG waves. Additionally, heart tissue was analyzed for macroscopic and microscopic changes. The results revealed significant electrocardiographic alterations, including pacemaker migration, junctional extrasystoles, and intraventricular conduction aberrations. By applying a linear regression algorithm, the study compensated for noise and anomalies in the isoelectric line in an ECG signal, improving the detection of P and T waves and the QRS complex with an efficiency of 97.5%. Cardiac enzyme evaluation indicated no statistically significant differences between the control and experimental groups. Macroscopic and microscopic examination revealed no apparent signs of damage or inflammatory responses in heart tissues. This study enhances our understanding of the cardiovascular impact of Heloderma venom, suggesting a greater influence on changes in conduction and arrhythmias than on direct cardiac damage to the myocardium.

The protective effect of benfotiamine on gastric ulcers in male rats: an experimental study.

Gastric ulcers are a common gastrointestinal disorder associated with significant morbidity and mortality. It can also increase the risk of gastric cancer. This study aimed to investigate the effect of benfotiamine on experimentally-induced gastric ulcers in male rats. In this study, 30 Wistar male rats were divided randomly into six groups: control (normal), indomethacin, omeprazole, and treatment groups, including 50, 100, and 200mg/kg of benfotiamine. Gastric ulcer was induced by indomethacin gavage. Omeprazole and different therapeutic doses of benfotiamine were administered for three days. Twenty-four hours after the last treatment, the rats were euthanized, and samples were collected.The results demonstrated that 100 and 200mg/kg of benfotiamine treatment significantly improved indomethacin-induced gastric tissue damage. Moreover, benfotiamine at 100 and 200mg/kg effectively attenuated the levels of pro-inflammatory cytokines IL-6 and TNF-α and oxidative stress markers MDA and ROS while increasing the antioxidant GSH. These findings suggest that benfotiamine's gastroprotective effects are mediated through its antioxidant and anti-inflammatory properties, which help mitigate the tissue damage and inflammatory response associated with indomethacin-induced gastric ulcers.However, further research is needed to elucidate the precise molecular mechanisms underlying these beneficial effects and to evaluate the potential therapeutic application of benfotiamine in clinical settings.

Vitamin E and GPX4 cooperatively protect treg cells from ferroptosis and alleviate intestinal inflammatory damage in necrotizing enterocolitis

BackgroundThe notable decline in the number of Tregs within Necrotizing enterocolitis (NEC) intestinal tissues，contribute to excessive inflammation and necrosis, yet the precise underlying factors remain enigmatic. Ferroptosis, a novel cell death stemming from a disrupted lipid redox metabolism, is the focus of this investigation. Specifically, this study delves into the ferroptosis of Treg cells in the context of NEC and observes the protective effects exerted by vitamin E intervention, which aims to mitigate ferroptosis of Treg cells. MethodsTo investigate the reduction of Treg cells in NEC intestine, we analyzed its association with ferroptosis from multiple angles. We constructed a mouse with a specific knockout of Gpx4 in Treg cells, aiming to examine the impact of Treg cell ferroptosis on NEC intestinal injury and localized inflammation. Ultimately, we employed vitamin E treatment to mitigate ferroptosis in NEC intestine's Treg cells, monitoring the subsequent amelioration in intestinal inflammatory damage. ResultsThe diminution of Treg cells in NEC is attributed to ferroptosis stemming from diminished GPX4 expression. Gpx4-deficient Treg cells exhibit impaired immunosuppressive function and are susceptible to ferroptosis. This ferroptosis of Treg cells exacerbates intestinal damage and inflammatory response in NEC. Notably, Vitamin E can inhibit the ferroptosis of Treg cells, subsequently alleviating intestinal damage and inflammation in NEC. Additionally, Vitamin E bolsters the anti-lipid peroxidation capability of Treg cells by upregulating the expression of GPX4. ConclusionIn the context of NEC, the ferroptosis of Treg cells represents a significant factor contributing to intestinal tissue damage and an exaggerated inflammatory response. GPX4 is pivotal for the viability and functionality of Treg cells. Vitamin E exhibits the capability to mitigate the ferroptosis of Treg cells, thereby enhancing their number and function, which plays a crucial role in mitigating intestinal tissue damage and inflammatory response in NEC.

Integration of levofloxacin-loaded spanlastics and prednisolone into a buccal mucoadhesive sponge for combating severe pneumonia: In-vitro/ex-vivo assessment, qRT-PCR analysis, and quantification of the HMGB-1/NF-қB signaling pathway

Pneumonia induced by Klebsiella pneumoniae (K. pneumoniae) is a grave pathological state that bears profound implications for morbidity and mortality rates. It is marked by an exaggerated inflammatory response in the lung tissue, resulting in lung damage. Accordingly, combining Levofloxacin hemihydrate (LV) with Prednisolone (PD) could potentially reduce the inflammatory response associated with severe pneumonia and save patients’ lives. Therefore, this study aimed to develop LV-loaded spanlastics (SPs)/PD buccal mucoadhesive sponge for the treatment of severe pneumonia. For LV SPs fabrication and optimization, a full 32 factorial design was utilized to examine the impact of the type of edge activator (EA) and Span 60: EA ratio on vesicle size (VS) and encapsulation efficiency percent (EE%). The optimum formula was determined by recording the minimum VS and maximum EE%. It was then tested microbiologically, followed by integration into a mucoadhesive sponge with the addition of PD, forming LV SPs/PD sponge that was evaluated via in-vivo study. The optimum LV SPs was formulation 3 (F3), which was fabricated using Tween 80 as an EA with a Span 60: EA ratio of 80:20. F3 exhibited an EE% of 92.40 ± 0.01 %, a VS of 248.60 ± 2.05 nm, highly elastic spherically shaped nanovesicles with a controlled release profile, and enhanced drug permeation. The minimum inhibitory concentration (MIC) of F3 was reduced by a factor of 8 compared to Levoxin®. Moreover, F3 revealed superiority over Levoxin® by 10, 20, and 10 percentage points increase in downregulating gyrA, gyrB, and parC gene expression in K. pneumoniae, respectively. The LV SPs/PD sponge revealed a spongy structure with well-defined pores. It had a surface pH of 6.93 ± 0.06, a swelling index of 3.52 ± 0.35, an ex-vivo mucoadhesion residence time of 3.01 ± 0.61 h, and a drug content of 97.39 ± 1.82 % for LV and 98.06 ± 1.34 % for PD. As well, the release pattern of the LV SPs/PD sponge was significantly slower than that of the F3 for LV and the Epicopred® for PD. The in-vivo study of the LV SPs/PD sponge demonstrated a prevalence effect in restoring the typical lung histology in rats. Additionally, it returns high mobility group box (HMGB)-1 and nuclear factor-kappa B (NF-қB) biomarkers to their normal levels, surpassing the effects observed with Levoxin®/Epicopred®. Collectively, the LV SPs/PD sponge might hold great potential as a promising treatment approach for the management of severe pneumonia.

Oculomotor nerve palsy caused by imidacloprid at initial diagnosis: A case report.

Amid the pervasive deployment of imidacloprid, the incidence of poisoning from this compound has risen markedly. Those afflicted with imidacloprid poisoning typically exhibit symptoms ranging from headaches, dizziness, nausea, and abdominal pain, to impaired consciousness and breathlessness, yet instances of ocular paralysis induced by this toxin have not previously been documented. When the pesticide spray inadvertently made contact with the patient's eyes, they were seared with a burning sensation and discomfort. Subsequent to this incident, on the second day, the individual began to experience diplopia in the right eye and found it arduous to elevate his eyelids, indicating a challenge in achieving full extension. Based on the medical history, symptoms, and signs, the patient was diagnosed with oculomotor nerve palsy caused by imidacloprid. The treatment involved intravenous dexamethasone to reduce inflammatory response in the eye tissue; oral pantoprazole enteric-coated tablets to suppress acid production and protect the stomach; Xuesaitong administered intravenously to improve blood supply to the eye and promote metabolism of toxins; vitamin C, cobamamide, and vitamin B1 for nerve nutrition and antioxidant effects; local application of tobramycin-dexamethasone eye drops for anti-inflammatory purposes; and repeated flushing of the conjunctival sac with saline. Finally, the patient improved and was discharged. After active treatment, the patient finally improved diplopia and ptosis. This report marks the first documentation of oculomotor nerve palsy induced by imidacloprid, featuring diplopia, and blepharoptosis without substantial limitation of ocular motility. Following therapeutic intervention, the patient showed marked improvement and was discharged from the hospital, providing a point of reference for the treatment of analogous cases in future clinical practice. It also serves as a reminder for the public to take appropriate precautions when using imidacloprid.

Accumulated inflammation and fibrosis participate in atrazine induced ovary toxicity in mice

Atrazine is a widely used herbicide in agricultural production. Previous studies have shown that atrazine affects hormone secretion and oocyte maturation in female reproduction. However, the specific mechanism by which atrazine affects ovarian function remains unclear. In this study, using a mouse gastric lavage model, we report that four weeks of atrazine exposure affects body growth, interferes with the estrous cycle, and increases the number of atretic follicles in mice. The expression levels of follicle development related factors StAR, BMP15, and AMH decreased. Metabolomic analysis revealed that atrazine activates an inflammatory response in ovarian tissue. Further studies confirmed that the expression levels of TNF-α, IL-6, and NF-κB increased in the ovaries of mice exposed to atrazine. Additionally, α-smooth muscle actin (α-SMA) accumulated in ovarian tissue, and transforming growth factor-β (TGF-β) signaling was activated, indicating the occurrence of tissue fibrosis. Moreover, mice exposed to atrazine produced fewer oocytes and exhibited reduced embryonic development. Furthermore, mice exposed to atrazine exhibited altered gut microbiota abundance and a disrupted colon barrier. Collectively, these findings suggest that atrazine exposure induces ovarian inflammation and fibrosis, disrupts ovarian homeostasis, and impairs follicle maturation, ultimately reducing oocyte quality.

L-Carnitine Ameliorates Amiodarone-Mediated Alveolar Damage: Oxidative Stress Parameters, Inflammatory Markers, Histological and Ultrastructural Insights.

The aim of this study was to assess L-carnitine's effects on adult male rats' lung damage brought on by amiodarone, which is a potent antiarrhythmic with limited clinical efficacy due to potentially life-threatening amiodarone-induced lung damage. Because of the resemblance among the structural abnormalities in rats' lungs that follows amiodarone medication and pulmonary toxicity in human beings, this animal model may be an appropriate example for this disease entity. Amiodarone produced pulmonary toxicity in twenty-four healthy male albino rats (150-180 g) over a period of 6 weeks. Four groups of six rats each were established: control, sham, amiodarone, and L-carnitine plus amiodarone. Histological, ultrastructural, oxidative stress, and inflammatory markers were determined during a 6-week exposure experiment. Amiodarone-induced lung damage in rats may be brought on due to oxidative stress producing significant pulmonary cytotoxicity, as evidenced by the disruption of the mitochondrial structure, severe fibrosis, and inflammatory response of the lung tissue. Lungs already exposed to such harmful effects may be partially protected by the antioxidant L-carnitine. Biochemical markers of lung damage brought on by amiodarone include lung tissue levels of the enzyme's catalase, superoxide dismutase, and reduced glutathione. The levels of lipid peroxides in lung tissue measured as malondialdehyde increased significantly upon exposure to amiodarone. In addition, the levels of tumor necrosis factor alpha were significantly elevated in response to amiodarone. The effect of L-carnitine on amiodarone-induced pulmonary toxicity was studied in rats. It is interesting to note that the intake of L-carnitine in rats treated with amiodarone partially restored the biochemical and histopathological alterations brought on by amiodarone to their original levels. Tumor necrosis factor alpha levels were significantly reduced upon L-carnitine exposure. These results suggest that L-carnitine can be used to treat amiodarone-induced pulmonary dysfunction.

The protective effects of orexin B in neuropathic pain by suppressing inflammatory response

Chronic pain induced by pathological insults to the sensorimotor system is a typical form of neuropathic pain (NP), and the underlying mechanism is complex. Currently, there are no successful therapeutic interventions for NP. Orexin B is a neuropeptide with a wide range of biological functions. However, the pharmacological function of orexin B in chronic neuropathic pain has been less studied. Here, we aim to examine the neuroprotective effects of orexin B in chronic constriction injury (CCI)- induced NP. Firstly, we found that orexin type 2 receptor (OX2R) but not orexin type 1 receptor (OX1R) was reduced in the spinal cord (SC) of CCI-treated rats. Mechanical withdrawal threshold and thermal withdrawal latency assays display that administration of orexin B clearly ameliorated CCI-evoked neuropathic pain dose-dependently. Notably, orexin B treatment also effectively prevented microglia activation by reducing the levels of IBA1. Additionally, orexin B was also found to suppress the inflammatory response in the SC tissue by reducing the levels of IL-6, TNF-α, iNOS, and COX-2 as well as the production of NO and PGE2 in CCI-treated rats. Furthermore, orexin B administration attenuated oxidative stress (OS) by increasing the activity of SOD and the levels of GSH. Mechanically, orexin B prevented activation of JNK/NF-κB signaling in the SC of CCI-treated rats. Based on these findings, we conclude that orexin B might have a promising role in ameliorating CCI-evoked neuropathic pain through the inhibition of microglial activation and inflammatory response.

Leveraging Hypotension Prediction Index to Forecast LPS-Induced Acute Lung Injury and Inflammation in a Porcine Model: Exploring the Role of Hypoxia-Inducible Factor in Circulatory Shock.

Acute respiratory distress syndrome (ARDS) is a critical illness in critically unwell patients, characterized by refractory hypoxemia and shock. This study evaluates an early detection tool and investigates the relationship between hypoxia and circulatory shock in ARDS, to improve diagnostic precision and therapy customization. We used a porcine model, inducing ARDS with mechanical ventilation and intratracheal plus intravenous lipopolysaccharide (LPS) injection. Hemodynamic changes were monitored using an Acumen IQ sensor and a ForeSight Elite sensor connected to the HemoSphere platform. We evaluated tissue damage, inflammatory response, and hypoxia-inducible factor (HIF) alterations using enzyme-linked immunosorbent assay and immunohistochemistry. The results showed severe hypotension and increased heart rates post-LPS exposure, with a notable rise in the hypotension prediction index (HPI) during acute lung injury (p = 0.024). Tissue oxygen saturation dropped considerably in the right brain region. Interestingly, post-injury HIF-2α levels were lower at the end of the experiment. Our findings imply that the HPI can effectively predict ARDS-related hypotension. HIF expression levels may serve as possible markers of rapid ARDS progression. Further research should be conducted on the clinical value of this novel approach in critical care, as well as the relationship between the HIF pathway and ARDS-associated hypotension.

Mechanisms of colon toxicity induced by long-term perfluorooctanoic acid exposure in mice

Perfluorooctanoic acid (PFOA), a persistent organic pollutant known for its chemical stability, is widely dispersed in the environment, posing significant health risks to mammals through various exposure routes such as ingestion, inhalation, and dermal contact. In this study, mice were exposed to PFOA (0, 0.2, 2 mg/L) through drinking water for 180 days to investigate its toxic effects on the colon. We identified differentially expressed genes through RNA sequencing and validated the impact of PFOA on the expression of these genes in colon tissue. Our findings revealed that long-term exposure to PFOA caused inflammatory bowel disease (IBD)-like damage to the mouse colon. We found PFOA could induce damage to the intestinal barrier. Inhibition of the Wnt signaling pathway following PFOA exposure results in impaired stem cell function in the colon of mice. Furthermore, PFOA activated the PPAR signaling pathway, disrupting cellular lipid metabolism in colon tissues. Additionally, PFOA induced inflammatory responses in colon tissue, facilitating NLR family, pyrin domain containing 3 (NLRP3) inflammasome activation and cell apoptosis. This study offers a thorough understanding of the mechanisms responsible for the damage to mouse colon tissue resulting from long-term exposure to PFOA.

Effect of peri-implant soft-tissue phenotype on peri-implant health

Dental implant is a commonly used therapeutic option for reconstruction of edentulous space. Adequate peri-implant soft tissue is crucial for preventing biological and esthetic complications. Peri-implant soft-tissue phenotypes including supracrestal tissue height, mucosa thickness and keratinized mucosa width could reflect the quality and quantity of peri-implant soft tissue. Different soft-tissue phenotypes might impact the stability of implant restoration through altering the tissue remodeling or inflammatory response. This review will discuss the influence of peri-implant soft-tissue phenotypes on tissue remodeling and inflammatory response after implant placement.