TNF-alpha Levels Research Articles

Effectiveness of Nigella sativa Addition against TNF-Alpha in Stage III and IV Breast Cancer Undergoing Doxorubicin and Cyclophosphamide Chemotherapy at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia

Background: Breast cancer is a malignancy caused by the continuous uncontrolled growth of the component cells of the ducts or lobules of the breast gland. Globally, breast cancer is the second leading cause of death in women. Nigella sativa contains substances thymoquinone. Thymoquinone can inhibit the progression of cancer through anti-inflammatory, anti-oxidant mechanisms, inhibit proliferation, trigger apoptosis, and prevent angiogenesis. Chronic inflammation in breast cancer is mediated by one of them is TNF-alpha tumors. Elevated levels of TNF-α have a significant association with poor prognosis and progression of breast cancer. This study aims to determine the effectiveness of the additional Nigella sativa in declining TNF-α levels in breast cancer patients at Dr. Mohammad Hoesin General Hospital Palembang.
 Methods: This research used a randomized, open clinical trial design, which was carried out at the internal medicine hematology-oncology medical polyclinic and the surgical oncology polyclinic of Dr. Mohammad Hoesin General Hospital Palembang from January 2023 to October 2023. Data processing for data analysis used SPSS version 26 for Windows.
 Results: There were 36 research subjects followed during the study period and received Doxorubicin chemotherapy and cyclophosphamide (AC), which were divided into treatment groups of 18 people (chemotherapy with the addition of Nigella sativa @600 mg 2x2 capsule/ day and a control group of 18 people. A TNF-alpha examination was carried out before and after to assess the comparison before and after. From the results, it was found that TNF-alpha levels in the treatment group showed a decrease in TNF-alpha with a p-value <0.001.
 Conclusion: The addition of Nigella sativa has the effect of reducing TNF-alpha in breast cancer patients receiving AC chemotherapy at Dr. Mohammad Hoesin General Hospital, Palembang.

Effects of photobiomodulation in the experimental acetic acid-induced colitis: comparison between male and female.

Ulcerative colitis (UC) is an important chronic and multifactorial disease, which alters the colon mucosal with a significant impact on life quality affecting both men and women. The difference between genders causes changes in the inflammatory processes, modulating the development of several diseases. The available drugs to treat UC exhibit limited outcomes and side effects; thus, new therapies are needed. Photobiomodulation (PBM) emerges as potential treatment by modulating the inflammatory process without side effects and low costs. The aim of this study was to evaluate the effects of PBM in acetic acid-induced UC comparing the responses between male and females. For this purpose, male and female Wistar rats (36) were submitted to induction of UC by rectal administration of 10% acetic acid (colitis group) and treated or not with PBM (colitis-PBM group) (LED, 660nm, 100 mW, 150s) in three points: right side and left of the ventral surface and in the external anal region. Non-manipulated rats were used as control (basal group). We investigated the disease activity index (DAI score), myeloperoxidase enzyme activity (MPO) and release of cytokines in the intestine homogenates, and histological analysis. PBM reduces DAI score, MPO activity, and mast cell degranulation while increased mucous production in both females and males. Moreover, PBM reduced histopathological score as well as the levels of IL-6 and IL-4 in the bowel only in males. We also showed reduced levels of IL-1beta and TNF-alpha after PBM in both males and females, while the levels of IL-10 and IFN-gamma were increased. In conclusion, despite our study has shown some differences between males and females, PBM attenuated the biomarkers of UC in both genders constituting a potential combined treatment that is non-invasive and low cost.

Olfactory receptor 2 signaling drives experimental abdominal aortic aneurysm formation

Abstract Background Abdominal aortic aneurysms (AAA) are defined as enlargement above 3cm or 50% of its original diameter. Therapeutic options are limited to surgical and endovascular treatment, while no pharmacological interventions are available. Chronic inflammation of the vessel wall and in particularly macrophage infiltration has been associated with disease progression, leading to extensive tissue remodeling, yet the underlying mechanisms are incompletely understood. A recent study has shown extra-nasal expression of the olfactory receptor 2 (OLFR2) on vascular macrophages, in which activation induced a pro-atherogenic response. The role of macrophage OLFR2 signaling in AAA, however, is unknown. Methods & Results To determine whether the OLFR2 ortholog OR6A2 is expressed in human AAA, we performed in silico micro-array analysis of human AAA tissue. OR6A2 was shown to be specifically upregulated in AAA tissue with thrombus formation compared to healthy control tissue. We confirmed OR6A2 expression on macrophages by immunofluorescence. To determine OLFR2 expression among vascular immune cells in mice, we induced AAA formation by porcine pancreas (PPE) infusion into the infrarenal aorta of C57BL6/J (WT) mice and performed spectral cytometry utilizing a 26-marker panel at baseline, day 7 and day 28. OLFR2 expression peaked at day 7 and decreased to baseline levels at day 28 particularly on pro-inflammatory monocytes, mixed resident / migratory-like macrophages and pro-inflammatory macrophages, while OLFR2 was not detectable on tissue resident-like macrophages. To assess a functional role of OLFR2 in AAA formation, we induced AAA in OLFR2-deficient (KO) mice and WT controls by PPE. Ultrasound analysis of the abdominal aorta revealed protection from AAA formation in KO mice. Histological analysis showed significantly reduced macrophage while increased smooth muscle cell content in aortic sections of KO mice compared to WT controls. This was accompanied by higher collagen content in KO mice. Additionally, plasma levels of the pro-inflammatory cytokines TNF-alpha and Interferon-gamma were significantly reduced in KO mice 28 days post PPE. Bulk transcriptome analysis corroborated these findings and indicated increased pathways associated with vascular smooth muscle cell contractility while decreased leukocyte activation in KO aortas. Conclusion We show that OLFR2 deficiency in mice attenuates abdominal aortic aneurysm development, aortic remodeling and pro-inflammatory response. OLFR2 might thus present a novel target for drug-based AAA therapies.

High-intensity interval training ameliorates spatial and recognition memory impairments, reduces hippocampal TNF-alpha levels, and amyloid-beta peptide load in male hypothyroid rats

Thyroid hormones are critical for healthy brain functions at every stage of life. Hypothyroidism can cause severe cognitive dysfunction in patients who do not receive adequate treatment. Although thyroid hormone replacement alleviates cognitive decline in hypothyroid patients, there are studies showing that there is no complete recovery. The aim of this study was to investigate the effects of high-intensity interval training (HIIT) in hypothyroid rats on spatial and recognition memory, neuroinflammation, amyloid-beta load and compare these effects with T3 replacement. Hypothyroidism was induced and maintained by administration of 6-n-propyl-2-thiouracil (PTU) with their drinking water to 6-weeks-old male Sprague–Dawley rats for 7 weeks. The animals exercised in the treadmill according to the HIIT protocol for four weeks. T3 was injected intraperitoneally daily during the last two weeks of the study. All animals performed in the elevated plus maze test, Morris water maze test, novel object recognition test, and rotarod motor performance test in the last week of the study and then the animals were sacrificed. Amyloid beta (1−42) and TNFα levels were measured in the prefrontal cortex and hippocampus by ELISA. Anxiety-like behaviors did not significantly differ between groups. T3 replacement with or without HIIT increased motor performance in PTU-treated rats. HIIT and/or T3 replacement increased the exercise performance. HIIT and/or T3 replacement alleviated spatial and recognition memory impairments and normalized TNFα and amyloid-beta levels in the hippocampus in hypothyroid rats. In summary, regular physical exercise may have potential benefits in preserving cognitive functions in hypothyroid patients.

CAR-NK Specific Targeting of Clonal Tcrvβ Chain to Treat T-Cell Non-Hodgkin's Lymphoma

Background T-cell Non-Hodgkin Lymphoma (T-NHL) is a diverse group of aggressive malignancies which are minimally researched and have poorer patient outcomes than those with B-cell NHL (Stuver et. al., 2022, Foss et. al., 2011). Therapies are characterized by pan T cell cytotoxicity, poor response rates and the requirement for multiple levels of treatments resulting in toxicity and suppression of the immune system that can lead to life threatening infections (Bellei et. Al., 2018). Clinical trials are considered a first line option for advanced disease, speaking to the lack of viable treatment options. One possible target for T cells is the T-cell receptor (TCR). TCRs possess tremendous diversity owing to diverse variable β chain (Vβ) (n=48) and α chain (Vα) (n=46) gene segments, that recombine with D and J gene segments to form a functional TCR. T Multiplexed PCR of the TCR gene has been used to identify the presence of a distinct malignant clone and facilitate diagnosis of T-NHL (Savage et. al., 2008). Thus, the Vβ chains represent a therapeutic target that discriminates the clonally expanded malignant T cells from the vast majority of healthy T-cells. Lucero et. al. (2023), showed specific targeting of T cell receptor Vβ chains, for T-NHL patients with an expanded TCRVβ clone using a naked antibody approach. Similar modalities have used BiTE and CAR-T. One downside of the naked antibody and BiTE approach (Paul et. Al., 2021) is that they require patients to have functional effector NK and CD8 T cells, and these cells are often not present in advanced T-NHL diseases. The expanded Vβ chain could also be targeted by CAR-T cell therapy; however, this approach is hampered by concerns of toxicity and poor autologous T cell quality due to the patients' disease (Marofi et. al., 2021). Therefore, we propose CAR-NK cell therapy utilizing the TCRVβ chain (Fig 1A) for patients with advanced T-NHL against the clonally expanded TCRVβ which will allow for an off the shelf approach that bypasses the need for autologous effector cells. Methods To show proof of concept, TCRVβ13 CAR-NK cells were manufactured from an NK-92 cell line, HaNK, which expresses a high affinity CD16 V158 FcγRIIIa receptor (Jochems, et. al., 2016). CAR transduction was confirmed via flow cytometry. Along with the CAR, NK/T-cell lymphoma cell lines, EL4 (mouse) and Jurkat (human), were transduced through a lentiviral vector containing a plasmid to express our Vβ of interest, Vβ13 (EL4-V13 and Jurkat-V13, respectively) (Lucero, 2023). We performed In vitro cytotoxicity co-culture assays on NK/T-cell lymphoma cell lines, EL4-V13 and Jurkat-V13, to confirm functional activity in CAR-HaNK cells compared to wild type HaNK cells at three different effector to target ratios. From the in vitro cytotoxicity assay, assays on supernatants from each of the co-cultures for changes of the cytokines INF-gamma and TNF-alpha levels to assess functional NK activity are in progress. Results The in vitro co-culture cytotoxicity assays showed increased cytotoxicity of the TCRVβ CAR-HaNK cells in comparison to HaNK cells in the presence of the TCRVβ for both EL-4-V13 and Jurkat-V13 cell lines. Targeting of the EL-4 cell line without the transduced TCRVβ showed similar percent cytotoxicity in CAR-HaNK cells and HaNK cells, while EL-4-V13 cell line showed significant increase in cytotoxicity when co-cultured with CAR-NK cells in comparison to the HaNK cells. In the 1:1 co-culture of either CAR-HaNK or HaNK cells with EL-4-V13 there was a 27% increase in cytotoxicity in the CAR-NK in comparison to the HaNK cells (P<0.0001), the 5:1 showed 71% increase in CAR-NK (P<0.0001), and the 10:1 showed an 80.5% increase in CAR-HaNK (P<0.0001) (Fig 1B). Similarly, in the human cell line Jurkat-V13, co-cultures with CAR-HaNK cells showed an increase in cytotoxicity in the 1:1 of 30% (P=0.0169), the 5:1 of 37% (P=0.0074), and 10:1 of 57.7% (P<0.0001) when comparing to HaNK cells (Fig 1B). Conclusions The goal of these preclinical studies is to leverage advances in CAR development with the efficacy of targeting TCRVβ as a direct and safe therapeutic option for patients with T-NHL. If successful, this will propel both cell-directed therapies and a novel target to a disease characterized by few efficacious, durable and safe therapies.

The protective effect of Lemon Peel Essential Oil on Pancreas and Brain Oxidative Stress and Inflammation induced by Streptozotocin-Nicotinamide in rats: Behavioral and Biochemical Evidences

The objective of this study is to investigate the effects of Moroccan lemon peel essential oil (LPEO) on various aspects such as anti-hyperglycemic, anti-inflammatory, antioxidant, and anxiolytic activities in diabetic rats. The animals were divided into five groups: normal control group, diabetic control group, diabetic group treated with metformin (300mg/kg), and two diabetic groups treated with LPEO at doses of 0.6ml/kg and 1.2ml/kg, respectively. T2DM was induced in the rats by administering intraperitoneal injections of Streptozotocin and Nicotinamide. Treatment with LPEO or metformin was initiated immediately after confirming the presence of hyperglycemia and continued for a duration of four weeks. Anxiety-related behavior in the rats was assessed using two behavioral tests. 24 hours after conducting the behavioral tests, all rats were anesthetized, and blood samples were taken for the analysis of lipid parameters. The pancreas and brain were dissected to assess TNF-alpha, SOD, and MDA levels. Treatments with LPEO contributed significantly to the preservation of lipid profile and reduction of the atherosclerosis index in diabetic rats (p<.05). Additionally, there was a notable decrease in MDA and TNF-α concentration in the pancreas and brain of diabetic rats treated with LPEO associated with a remarkable increase in SOD activity in the pancreas and brain compared to diabetic control group (p<.05). Lastly, both LPEO and metformin treatments demonstrated significant improvements in anxiety-related behavior in this rat model (p<.05). These positive effects could potentially be attributed to the potent antioxidant and anti-inflammatory activities of both treatments.

Molecular Characterisation of Blood Microbiome in Patients with Ankylosing Spondylitis and Healthy Controls.

In human and animal studies, ankylosing spondylitis (AS) has been increasingly linked to changes in the microbial inhabitants in the human body (microbiome). These studies have primarily now concentrated on the microbial communities that live in the gastrointestinal tract. However, evidence suggests that various molecular techniques can be used to detect microbial DNA in blood circulation. This DNA might be an unknown reservoir of biomarkers with the potential to track alterations in the microbiomes of remote locations, such as the gut. To this end, we compared the presence and identity of microbial DNA in blood samples taken from ankylosing spondylitis patients to healthy control subjects by amplifying and sequencing the bacterial 16S rRNA variable region four. The study's design is a case study based on the presence and identity of bacterial DNA in the blood of Ankylosing spondylitis (AS) patients (n = 10) and healthy control subjects (n = 10) was investigated by amplifying and sequencing the bacterial 16S rRNA gene. Blood concentrations of the cytokines TNF alpha, IL-17A, and IL-23 were determined by the Human Magnetic Luminex Screening, and data were analysed using an Unpaired T-test. Using PCR amplification, 8 of 10 AS patients (80%) and 8 of 10 healthy control samples (80%) had microbial 16S rRNA in their blood. At the phylum level, Proteobacteria (Control = 48.5%, AS = 52%), Firmicutes (Control = 27.8%, AS = 26.1%), Actinobacteria (Control = 15.4%, AS = 10.7%), and Bacteroidetes (Control = 6.5%, AS = 10%) dominated the blood microbiome. A two-tailed Mann-Whitney test found that Ankylosing Spondylitis was associated with significantly elevated Bacteroides (P < 0.05), Prevotella (P < 0.001), and Micrococcus (P < 0.01), and significantly reduced levels of Corynebacterium 1 (P < 0.001), Gemella (P < 0.01), and Alloprevotella (P < 0.05), compared to healthy controls. Additionally, it was shown that the presence of the Prevotella genus was highly positively correlated with higher levels of TNF-alpha (P < 0.05; r = 0.8) in AS patients' blood. This article reveals that a blood microbiome exists in healthy individuals and identifies particular taxa modulated in disease. These blood-derived signatures indicate that this field needs more research and may be helpful as disease biomarkers.

Behavioral Effects and Analgesic Profile of Hemoglobin-Derived Valorphin and Its Synthetic Analog in Rodents.

Valorphin (V1) is a naturally occurring peptide derived from hemoglobin that has been found to have an affinity for opioid receptors and exhibits antinociceptive and anticonvulsant activity. Some of its synthetic analogs containing an aminophosphonate moiety show structure-dependent potent antinociceptive effects. This study aimed to reveal a detailed picture of the antinociceptive mechanisms and behavioral effects of V1 and its recently synthesized phosphopeptide analog V2p in rodents using a range of methods. The studied peptides significantly reduced acute (mean V1-9.0, V2p-5.8 vs. controls-54.1 s) and inflammatory (mean V1-57.9 and V2p-53.3 vs. controls-107.6 s) nociceptive pain in the formalin test, as well as carrageenan-induced hyperalgesia (mean V1-184.7 and V2p-107.3 vs. controls-61.8 g) in the paw pressure test. These effects are mediated by activation of opioid receptors with a predominance of kappa in V1 antinociception and by delta, kappa, and mu receptors in V2p-induced antinociception. Both peptides did not change the levels of TNF-alpha and IL-1-beta in blood serum. V1 induces depression-like behavior, and V2p shows a tendency toward anxiolysis and short-term impairment of motor coordination without affecting exploratory behavior. The results characterize valorphin and its derivative as promising analgesics that exert their effects both centrally and peripherally, without causing severe behavioral changes in experimental animals. These encouraging data are a foundation for future studies focusing on the effects of hemorphins after long-term treatment.

Plasma Levels of Organochlorine Pesticides and Tumor Necrosis Factor-Alpha: A Potential Risk Factor for Developing Acquired Aplastic Anemia in the North Indian Population.

Background Pesticide exposure might have a contributory role in the development ofacquired aplastic anemia (AA). However, the precise mechanisms of pesticide-induced AA remain unknown. In this case-control study, we conducted a comparative analysis of plasma levels of organochlorine pesticides (OCP) and tumor necrosis factor-alpha (TNF-alpha) between Indian patients diagnosed with AA and an age- and sex-matched control group. Methods This is an observational case-controlstudy conducted at a tertiary care hospital in North India. In this study, 90 subjects were included, out of which 45 were diagnosed with AA according to the criteria of the International Agranulocytosis and Aplastic Anemia Study. Cases were compared with 45 controls. A trained interviewer gave all study subjects a questionnaire to collect data regarding demographic details, exposure to pesticides, and clinical history.Physical examinationand routine laboratory investigations of each subject were performed. Both cases and controls were tested for their plasma levels of organochlorines as per established protocol by gas chromatography-mass spectrometry. TNF-alpha level was measured by enzyme-linked immunosorbent assay in each subject. Results There was a significant increase in plasma levels of delta hexachlorocyclohexane(delta HCH) (p = 0.02) and heptachlor (p = 0.00) in patients with AA as compared to controls. We observed nonsignificant trends towards higher levels of beta HCH (p = 0.643), aldrin (p = 0.399), and p,p'-Dichlorodiphenyltrichloroethane (p,p'-DDT) (p = 0.453) in patients with AA when compared to the controls. There were significantly higherTNF-alpha levels (p = 0.024) in cases as compared to the controls. Conclusion Our study concludes that patients with AA exhibited higher levels ofdelta-HCH, heptachlor, andTNF-alpha in comparison to the control group. There is a significant positive correlation of TNF alpha with OCPs (alpha HCH, lindane, delta HCH, heptachlor, aldrin, p,p'- DDD, and methoxychlor pesticides). These organochlorines may have accumulated in the fatty tissue of bone marrow because of their lipophilic nature. This suggests that they might have served as a neoantigen to trigger an increase in TNF-alpha production, which may have led to disrupted bone marrow function through cell-mediated immunity, leading to AA.

Association Between Perceived Stress and Salivary Biomarkers of Allostatic Load Among Gender Minorities in Chennai: An Observational Cross-Sectional Study.

Background Transgender individuals in India experience immense psychosocial stressors, stigma, and violence. In response to stress, the body exhibits adaptive responses that necessitate the production of organic chemicals ensuing in the detection of blood serum and saliva.There are currently no laboratory tests that are confirmatory for the diagnosis of stress and facilitate necessary treatment to be carried out in a timely manner. Thus, potential salivary biomarkers could be a helpful tool in overseeing the efficacy of pharmacological treatment prescribed by a psychiatrist. Aim This study aimed to assess the correlation between perceived stress and salivary stress biomarker levels in transgender and gender nonconforming (TGNC) individuals in Chennai, India. Methodology Twenty-two TGNC individuals and 22 age-matched controls in Chennai were administered the Perceived Stress Scale-10 questionnaire. Following this, their saliva samples were collected using the passive drool technique and subjected to sandwich enzyme-linked immunosorbent assay (ELISA) technique for measuring salivary cortisol, salivary tumor necrosis factor-alpha (TNF-alpha), and salivary C-reactive protein (CRP). Independent t-test was used to compare salivary stress biomarker levels between the TGNC and age-matched control groups. Pearson's correlation test was done to correlate perceived stress and salivary stress biomarker levels in the TGNC group. Results Significant difference was seen between the TGNC and control groups with respect to salivary cortisol and salivary TNF-alpha levels, with the levels being higher in the TGNC group. A significant positive correlation was seen between perceived stress and salivary cortisol and between perceived stress and salivary TNF-alpha levels. Conclusion There is a significant correlation between perceived stress and salivary biomarkers of stress among TGNC people in Chennai.

Comparison of Efficacy and Safety Between Video- Assisted Thoracoscopic Surgery and Traditional Thoracotomy in the Treatment of Esophageal Cancer

Objective: To compare the therapeutic effect of video-assisted thoracoscopic surgery and traditional thoracotomy in patients with esophageal cancer. Methods: 60 patients with esophageal cancer who were treated from February 2022 to February 2023 were randomly divided into groups. Video-assisted thoracoscopic surgery was included in group A, and thoracotomy was included in group B. The curative effects of esophageal cancer surgery were compared. Results: All surgical indexes in group A were better than those in group B (P &lt; 0.05); interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) levels in group A were lower than those in group B (P &lt; 0.05); the postoperative SF-36 score in group A was higher than that in group B (P &lt; 0.05); the postoperative complication rate in group A was lower than that in group B (P &lt; 0.05). Conclusion: Video-assisted thoracoscopic treatment for patients with esophageal cancer can reduce postoperative inflammatory response and reduce surgical trauma, which is safe and efficient.

An Experimental Rat Model Study: Is There Any Effect of Syringic Acid on Ischemia-Reperfusion Injury in Priapism?

Purpose The purpose of this research is to examine the impact of syringic acid on ischemia-reperfusion injury in cavernosal tissue, utilizing a rat model of induced priapism. Materials and methods A total of 24 rats were allocated into three groups. Group 1 was designated as the control group, while Group 2 underwent ischemia-reperfusion injury assessment using the priapism model. Group 3 underwent the same procedures as Group 2, with the addition of intraperitoneal administration of syringic acid (100 mg/kg) 60 min after priapism initiation. All rats underwent penectomy, and sufficient blood samples were collected. Histopathological assessment of penile cavernosal tissue involved grading tissue damage, inflammation, vasocongestion, desquamation, and edema on a scale of 0-3 (0: normal, 1: mild,2: moderate, 3: severe). Result Significant differences were observed among the three groups in terms of IL-1 beta and TNF-alpha levels (p=0.001 and p<0.001, respectively).IL-1 beta and TNF-alpha levels in Group 2 were found to be significantly higher than Group 3 (p=0.003 and p=0.004).There was also a significant difference among the three groups in terms of median MDA levels (p<0.001). Furthermore, the median MDA level in Group 2 was found to be significantly higher than that in Group 3 (p<0.001). While significant differences were observed among the three groups in terms of median SOD and GSH-px levels, no significant difference was found among the groups in terms of median PC levels (p=0.004, p= 0.048, and p=0.159,respectively). In direct microscopic examination, a significant improvement in pathological scores was noted in Group 3 compared to Group 2 (p<0.001). Conclusion Syringic acid demonstrated protective properties against ischemia-reperfusion injury caused by priapism in cavernosal tissue.

Serum Inflammatory Cytokine Levels in Herpes Zoster Patients and Their Association with Postherpetic Neuralgia: A Prospective Study.

BACKGROUND This study aimed to investigate the serum levels of inflammatory cytokines in patients with herpes zoster (HZ) and to assess their correlation with the development of postherpetic neuralgia (PHN). Understanding this relationship may offer insight into the mechanisms of PHN and provide avenues for targeted treatment. MATERIAL AND METHODS We selected 169 patients diagnosed with HZ and 43 healthy controls (HCs) for the study. Serum levels of inflammatory cytokines were measured in all participants. Pain severity was evaluated using the visual analog scale (VAS). Based on follow-up data, the 169 HZ patients were categorized into 2 groups: those who developed PHN (HZ-PHN) and those who did not (HZ-Con). We then analyzed the differences in cytokine levels and their correlation with PHN development. RESULTS Compared to the HCs group, HZ patients exhibited a significant decrease in TNF-a levels and an increase in IL-10 levels (P<0.05, P<0.01). The VAS score was negatively correlated with TNF-alpha levels and positively correlated with IL-10 levels in HZ patients (r=-0.3081, P<0.01; r=0.5619, P<0.01). Distinctive levels of TNF-alpha, IL-6, IL-8, and IL-10 were observed among different pain groups (P<0.05, P<0.01). The HZ-PHN group showed lower TNF-alpha and higher IL-10 levels compared to the HZ-Con group (P<0.05, P<0.01). IL-10 level was identified as an independent risk factor for PHN, with a sensitivity and specificity of 76.4% and 54.3%, respectively. CONCLUSIONS Abnormal levels of inflammatory cytokines are present in HZ patients, and the IL-10 level may serve as a valuable indicator for predicting the risk of developing PHN.

PPARG stimulation restored lung mRNA expression of core clock, inflammation- and metabolism-related genes disrupted by reversed feeding in male mice.

The circadian rhythm system regulates lung function as well as local and systemic inflammations. The alteration of this rhythm might be induced by a change in the eating rhythm. Peroxisome proliferator-activated receptor gamma (PPARG) is a key molecule involved in circadian rhythm regulation, lung functions, and metabolic processes. We described the effect of the PPARG agonist pioglitazone (PZ) on the diurnal mRNA expression profile of core circadian clock genes (Arntl, Clock, Nr1d1, Cry1, Cry2, Per1, and Per2) and metabolism- and inflammation-related genes (Nfe2l2, Pparg, Rela, and Cxcl5) in the male murine lung disrupted by reversed feeding (RF). In mice, RF disrupted the diurnal expression pattern of core clock genes. It decreased Nfe2l2 and Pparg and increased Rela and Cxcl5 expression in lung tissue. There were elevated levels of IL-6, TNF-alpha, total cells, macrophages, and lymphocyte counts in bronchoalveolar lavage (BAL) with a significant increase in vascular congestion and cellular infiltrates in male mouse lung tissue. Administration of PZ regained the diurnal clock gene expression, increased Nfe2l2 and Pparg expression, and reduced Rela, Cxcl5 expression and IL-6, TNF-alpha, and cellularity in BAL. PZ administration at 7 p.m. was more efficient than at 7 a.m.

Curcumin in vitro Neuroprotective Effects Are Mediated by p62/keap-1/Nrf2 and PI3K/AKT Signaling Pathway and Autophagy Inhibition.

Oxidative stress and autophagy are potential mechanisms associated with cerebral ischemia/reperfusion injury (IRI) and is usually linked to inflammatory responses and apoptosis. Curcumin has recently been demonstrated to exhibit anti-inflammatory, anti-oxidant, anti-apoptotic and autophagy regulation properties. However, mechanism of curcumin on IRI-induced oxidative stress and autophagy remains not well understood. We evaluated the protective effects and potential mechanisms of curcumin on cerebral microvascular endothelial cells (bEnd.3) and neuronal cells (HT22) against oxygen glucose deprivation/reoxygenation (OGD/R) in vitro models that mimic in vivo cerebral IRI. The cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) activity assays revealed that curcumin attenuated the OGD/R-induced injury in a dose-specific manner. OGD/R induced elevated levels of inflammatory cytokines TNF-alpha, IL-6 as well as IL-1beta, and these effects were notably reduced by curcumin. OGD/R-mediated apoptosis was suppressed by curcumin via upregulating B-cell lymphoma-2 (Bcl-2) and downregulating Bcl-associated X (Bax), cleaved-caspase3 and TUNEL apoptosis marker. Additionally, curcumin increased superoxide dismutase (SOD) and glutathione (GSH), but suppressed malondialdehyde (MDA) and reactive oxygen species (ROS) content. Curcumin inhibited the levels of autophagic biomarkers such as LC3 II/LC3 I and Beclin1. Particularly, curcumin induced p62 accumulation and its interactions with keap1 and promoted NF-E2-related factor 2 (Nrf2) translocation to nucleus, accompanied by increased NADPH quinone dehydrogenase (Nqo1) and heme oxygenase 1 (HO-1). Treatment of curcumin increased phosphorylation-phosphatidylinositol 3 kinase (p-PI3K) and p-protein kinase B (p-AKT). The autophagy inhibitor 3-methyladenine (3-MA) activated the keap-1/Nrf2 and PI3K/AKT pathways. This study highlights the neuroprotective effects of curcumin on cerebral IRI.

Serum level of certain cytokines associated with psoriasis progression in Iraqi patients

Introduction and Aim: Psoriasis is a skin ailment that typically affects the scalp, lower back, knees, elbows, and results in flaky skin patches. The purpose of this study was to compare cytokines, leptin, and adiponectin levels, as well as several physiological characteristics, in psoriasis patients with and without treatment to levels in healthy people in Iraq. Materials and Methods: The study included 310 subjects, males and females aged (25-65) years. The patients were attending a dermatology consultant at Al-Yarmouk Teaching Hospital in Baghdad. Blood samples were collected by venipuncture from all individuals. The Sandwich ELISA was used to estimate serum levels of IL-2, IL-8, IL-22, TNF-alpha, IFN-gamma, ADP and Leptin. Results: Patients with psoriasis had considerably decreased lymphocyte and RBC counts while having significantly higher neutrophil, platelet, NLR, and PLR counts. WBC mean values in females and males among control groups were 7.16 ± 3.09x 103/µl and 8.6 ±3.62 x103/µl respectively. In psoriasis patients the WBC counts varied from 3.69 x103/µl to 12.8 x103/µl with a mean of 7.27 x 103/µl in female patients and from 6.47 x 103/µl to 13.62 x103/µl in males. Serum levels of cytokines, leptin and adiponectin were significantly higher in Group I patients, while in Group II it was almost like levels in the control group. Conclusion: Smoking is a risk factor for psoriasis. Lymphocytes, erythrocytes, and hemoglobin levels are decreased in patients with psoriasis, while platelets and cytokines are elevated, signifying a relationship between these immunological parameters and development and severity of psoriasis disease.

Effects of Different Ozone Doses Added to the Antibiotic Treatment on Cytokine Levels in Experimental Sepsis Model

We aimed to examine the changes caused by ozone therapy added to the antibiotic treatment on proinflammatory and anti-inflammatory cytokine levels in an experimental sepsis model formed with E. coli endotoxin. Rats were divided into 6 groups of 10 rats. Sepsis was formed by dosing 5 groups of rats with intraperitoneal E. coli endotoxin injection. For the first 3 groups, 0.6 mg/kg, 0.9 mg/kg, and 1.1 mg/kg doses of ozone therapy were added to the antibiotic treatment and group-4 only received antibiotic treatment. Group-5 was not treated. Group-6 received intraperitoneal serum physiologic injection simultaneously with the other groups. All treatments were sustained for 5 days. IL-1, IL-10, and TNF-alpha levels were detected in blood serum taken from rats sacrificed on day 6. It was seen that IL-1, TNF-alpha levels are significantly lower than the levels in other groups that received ozone therapy. In the comparisons amongst the groups receiving ozone therapy, it was observed that IL-1 levels do not have a significant difference and TNF-alpha levels are significantly lower in the two groups receiving lower doses than the group receiving a higher dose. There were no significant differences detected between groups at serum levels of IL-10 which is an anti-inflammatory cytokine. It was concluded that ozone added to the antibiotic treatment in sepsis could have a positive effect on survival rates by suppressing inflammatory process.

Abstract P2115: (2R,6R)-Hydroxynorketamine Prevents Myocardial Ischemia Reperfusion Injury By Regulating Immune And Inflammatory Response

Background: The ketamine metabolite 2R,6R-hydroxynorketamine (HNK) has recently attracted increasing attention by its potential as a novel fast-acting antidepressant candidate to treat depression. HNK has anti-inflammatory properties which contribute to its protective effects against ischemia and reperfusion (I/R) injury. However, whether HNK produces beneficial effects on myocardial I/R injury has not been elucidated yet. Here we tested the hypothesis that HNK might protects the heart from myocardial I/R injury by limiting myocardial inflammation. Methods and Results: Twelve male C57BL/6J mice (8-10 weeks old, 20-25 g) were used to produce acute myocardial I/R (30 min/24 h) by micro-surgery. Mice were divided into four groups: Sham, HNK+Sham, I/R, HNK+I/R. A single-dose of HNK (30 mg/kg) was intraperitoneally injected one hour before the I/R. Echocardiographic imaging and TTC staining showed that HKN administration before myocardial I/R increased fraction shortening by 26.5% and limited infarct size by 40% compared to I/R alone. Proteomics analysis showed HNK caused 81 proteins down-regulated and 18 proteins up-regulated in the left ventricle after I/R (HNK+I/R vs . I/R). The gene name of the top 5 down-regulated proteins are Ighg2b, Igkv17-121, Igkc, Igtp and Cd68. The go enrichment analysis showed that HNK in the I/R group could modulate immune response via downregulating signal transducer and activation of transcription 1 and 2 (STAT1 and STAT2) and type 1 interferon pathway. The KEGG enrichment analysis showed that HNK affected antigen processing and presentation via down-regulating beta-2-microglobulin, TAPBP and TAP1/2. Cytokine analysis showed that HNK attenuated the increased tissue levels of TNF-alpha, IL-1 beta, CTnI and BNP induced by I/R. HNK also significantly decreased I/R induced-neutrophil infiltration, apoptosis and oxidative stress in the myocardium as detected by Ly6G staining, tunel staining and DHE probe staining. Conclusion: We demonstrated for the first time the administration of HNK regulates immune response through STAT1 and STAT2 and type 1 interferon pathway in the heart, leading to the cardioprotection against I/R injury. The use of HNK may become an immunomodulatory therapy for the ischemic heart disease.

Correlation between H. pylori infection and serum levels of inflammatory markers: A retrospective study

Infection with Helicobacter pylori (H. pylori) is a significant issue that affects gastrointestinal health on a global scale. It has been related to several severe side effects, including gastritis, peptic ulcers, and stomach cancer. Identifying reliable biomarkers for early detection and monitoring of H. pylori infections is crucial for improving patient outcomes. Our study aimed to analyze laboratory variables as potential biomarkers for detecting and evaluating H. pylori infections. To achieve this, we conducted retrospective research using information from 500 patients with and without H—pylori infection. C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), vitamin D3 levels, alanine transaminase (ALT), and aspartate transaminase (AST) were among the laboratory variables we gathered and examined. Descriptive statistics and correlation analyses were used in our study. The findings of our study imply that CRP and IL-6 levels show potential as markers of the inflammatory response brought on by H. pylori infection. Additionally, we found that vitamin D3 deficiency may influence how infected patients' immune systems react to this pathogen. However, none of the characteristics under research or the TNF-alpha levels we found were significantly correlated with H. pylori infection. The conclusions drawn from our study offer important information on potential biomarkers for identifying and keeping track of H. pylori infections. We can ultimately improve patient outcomes and lessen the burden of sickness this pathogen brings by enhancing the detection and evaluation of H. pylori infections. More research is required to confirm.

Mice prenatally exposed to valproic acid do not show autism-related disorders when fed with polyunsaturated fatty acid-enriched diets

Dietary supplementations with n-3 polyunsaturated fatty acid (PUFA) have been explored in autism spectrum disorder (ASD) but their efficiency and potential in ameliorating cardinal symptoms of the disease remain elusive. Here, we compared a n-3 long-chain (LC) PUFA dietary supplementation (n-3 supp) obtained from fatty fish with a n-3 PUFA precursor diet (n-3 bal) obtained from plant oils in the valproic acid (VPA, 450 mg/kg at E12.5) ASD mouse model starting from embryonic life, throughout lactation and until adulthood. Maternal and offspring behaviors were investigated as well as several VPA-induced ASD biological features: cerebellar Purkinje cell (PC) number, inflammatory markers, gut microbiota, and peripheral and brain PUFA composition. Developmental milestones were delayed in the n-3 supp group compared to the n-3 bal group in both sexes. Whatever the diet, VPA-exposed offspring did not show ASD characteristic alterations in social behavior, stereotypies, PC number, or gut microbiota dysbiosis while global activity, gait, peripheral and brain PUFA levels as well as cerebellar TNF-alpha levels were differentially altered by diet and treatment according to sex. The current study provides evidence of beneficial effects of n-3 PUFA based diets, including one without LCPUFAs, on preventing several behavioral and cellular symptoms related to ASD.