Impacts of 18F-FDG PET/CT Parameters on Differential Diagnosis and Outcome of Patients with Primary Invasive Mucinous and Lepidic Predominant Adenocarcinoma of the Lung.

Objectives: The purpose of this study was to investigate whether 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters have a role in differentiating invasive mucinous lung adenocarcinoma (IMA) from lepidic predominant lung adenocarcinoma (LPA). Additionally, we compared the 18F-FDG-PET/CT features between survivors and non-survivors. Methods: Tumors were divided into 2 groups according to CT appearance: Group 1: nodular-type tumor; group 2: mass- or pneumonic-type tumor. Unilateral and bilateral multifocal diseases were detected. Clinicopathological characteristics and PET/CT findings were compared between IMAs and LPAs, as well as between survivors and non-survivors. Results: We included 43 patients with IMA and 14 with LPA. Tumor size (p=0.003), incidence of mass/pneumonic type (p=0.011), and bilateral lung involvement (p=0.049) were higher in IMAs than in LPAs. IMAs had more advanced T, M, and Tumor, Node, and Metastasis stages than in LPAs (p=0.048, p=0.049, and p=0.022, respectively). There was no statistically significant difference in maximum standardized uptake value (SUVmax) between the IMA and LPA (p=0.078). The SUV was significantly lower in the nodular group than in the mass/pneumonic-type group (p=0.0001). A total of 11 patients died, of whom SUVmax values were significantly higher in these patients (p=0.031). Male gender (p=0.0001), rate of stage III-IV (p=0.0001), T3-T4 (p=0.021), M1 stages (p=0.0001), multifocality (p=0.0001), and bilateral lung involvement (p=0.0001) were higher in non-survivor. Conclusions: Although CT images were useful for the differential diagnosis of LPAs and IMAs, SUVmax was not helpful for differentiation of these 2 groups. However, both 18F-FDG uptake and CT findings may play an important role in predicting prognosis in these patients.

After 30 Years of Remission, Recurrence With Renal Cell Carcinoma Metastasis Mimicking Pancreatic Neuroendocrine Tumor on 18F-FDG and 68Ga-DOTATATE PET/CT.

ABSTRACT: A 75-year-old man with a previous history of left nephrectomy for clear cell renal cell carcinoma in remission was underwent 68Ga-DOTATATE PET/CT imaging for evaluation of pancreatic body lesion. It showed a mass with intense 68Ga-DOTATATE uptake in the pancreatic corpus. During the follow-up of the patient who did not want to undergo surgery, 18F-FDG PET/CT scan was performed due to the increase in the size of the mass, and mild FDG uptake was detected in the pancreatic corpus lesion, and histopathological examination was confirmed as renal cell carcinoma metastasis.

Intratracheal Ectopic Thyroid Tissue Mimicking a Subglottic Mass in a Patient With Thyroid Follicular Carcinoma on SPECT/CT.

ABSTRACT: Intratracheal ectopic thyroid tissue is an extremely rare condition with limited cases reported in the literature. It can be asymptomatic or present with symptoms such as dysphagia, bleeding, dysphonia, dyspnea, and a sensation of a foreign body in the throat, depending on its localization. Due to its various clinical presentations, it poses a diagnostic dilemma. Herein, we aimed to present the contribution of thyroid scintigraphy and SPECT/CT to the diagnosis and management of a case with follicular carcinoma in the orthotopic thyroid gland as well as an ectopic intratracheal thyroid causing cough and airway obstruction mimicking a subglottic mass.

The role of different antioxidant pathways like AKT, SIRT-1, NRF2 and HO-1 in cardiac damage after subarachnoid hemorrhage.

AIM: The aim of this study was to explore the pathophysiological mechanism of subarachnoid haemorrhage (SAH) using cellular oxidative stress mechanisms and inflammation. MATERIAL AND METHODS: A total of 20 Wistar Albino rats were divided into two groups, namely sham and SAH. On day 0, 0.3 mL of saline in the sham group and 0.3 ml of autologous blood in the SAH group were applied in the cisterna magna of the animals. After scarification on the 7th day of the procedure, brain, blood and heart tissues were collected. In different tissues, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), creatin kinase MB (CKMB) and lactate dehydrogenase (LDH) levels were detected biochemically. AKT, sirtuin-1 (SIRT-1), NF-E2-related factor 2 (NRF2), heme oxygenase-1 (HO-1) genes and glutathione peroxidase-4 expression were examined genetically. Moreover, histopathological analyses were conducted both in heart and brain tissues. RESULTS: Enhanced TOS, OSI levels in all tissues and glial fibrillary acidic protein (GFAP) expressions in brain tissue and NFkß, IL-6 and Cox-1 expressions in heart tissues; it was observed that levels of TAS in blood and AKT, SIRT-1, NRF2 and HO-1 gene expressions in brain tissue were decreased. CONCLUSION: In the oxidative stress and inflammation situation that takes place following SAH, AKT, SIRT-1, NRF2 and HO-1 pathways, which are antioxidant mechanisms, are suppressed and GFAP, NFkß, IL-6, Cox-1 expressions, which trigger inflammation, are enhanced. Treatment of SAH necessitates studies on the inhibition or activation of such pathways.

Dapagliflozin prevents reproductive damage caused by acute systemic inflammation through antioxidant, anti-inflammatory, and antiapoptotic mechanisms.

Dapagliflozin (DPG) is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that has been suggested to possess anti-inflammatory properties in diabetes. The aim of this study is to evaluate the role of DPG administration in preventing lipopolysaccharide (LPS)-induced damage in the female genital system. Thirty-two female Wistar Albino rats were randomly allocated into four groups: control group, LPS group, LPS + DPG group and DPG group. At the end of the experimental phase, ovary, fallopian tube and uterus tissues were collected for histopathological, immunohistochemical, genetic and biochemical analyses. The findings showed that LPS caused histopathological changes characterized by marked hyperaemia, mild to moderate haemorrhage, oedema and neutrophil leucocyte infiltrations and degenerative and necrotic changes in the female genital tract. In addition, it decreased total antioxidant status (TAS), increased total oxidant status (TOS) and oxidative stress index (OSI) levels. LPS also increased the expressions of Cas-3, G-CSF and IL-1ß in the ovary, fallopian tubes and uterus immunohistochemically. While Claudin-1 expression decreased, NLRP3 and AQP4 gene expressions increased due to LPS. However, DPG treatment prevented all these changes. The results of this study indicate that, DPG can be used to prevent LPS-induced lesions in the female reproductive system.

The renoprotective effects of cannabidiol on lipopolysaccharide-induced systemic inflammation model of rats.

Sepsis-induced renal damage poses a significant threat, necessitating effective therapeutic strategies. Cannabidiol (CBD) has beneficial effects on tissues and their functions by exhibiting antioxidant and anti-inflammatory effects. This study investigates the potential protective effects of CBD in mitigating lipopolysaccharide (LPS)-induced renal injury in Wistar Albino rats. Thirty-two Wistar Albino rats were categorized into control, LPS (5 mg/kg i.p.), LPS + CBD, and CBD (5 mg/kg i.p.) groups. After the experiment, samples were collected for biochemical, genetic, histopathological, and immunohistochemical analyses. Oxidative stress markers as total oxidant status (TOS) and total antioxidant status (TAS), oxidative stress index (OSI), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), immune staining as tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), caspase-3, gene expressions as nuclear factor erythroid 2-related factor 2 (NRF2), C/EBP homologous protein (CHOP), caspase-9, glucose-regulating protein 78 (GRP78), B-cell leukemia/lymphoma 2 (Bcl2), and tissue histology have been examined. The LPS-exposed group exhibited significant renal abnormalities, mitigated by CBD intervention in the LPS + CBD group. CBD reduced immunoexpression scores for TNF-α, caspase-3, and IL-10. Biochemically, CBD induced a positive shift in the oxidative balance, increasing TAS, SOD, and GPx, while decreasing TOS, OSI, and MDA levels. Genetic analyses highlighted CBD's regulatory impact on NRF2, CHOP, caspase-9, GRP78, and Bcl2, providing molecular insights into its protective role against LPS-induced renal damage. This study underscores CBD as a promising protective agent against sepsis-induced renal damage. Our findings could provide valuable insights into potential therapeutic avenues for addressing renal complications in sepsis.

"Investigation of the potential cellular changes induced by magnesium sulfate and salubrinal in a lipopolysaccharide-induced chorioamnionitis model".

Chorioamnionitis is closely associated with preterm labor and poses a significant public health concern. In this pathological process where inflammation plays a key role, intracellular mechanisms such as endoplasmic reticulum stress are crucial. In this study, we aimed to explore the potential positive outcomes of the combined use of salubrinal (SLB) with magnesium (Mg) treatment in chorioamnionitis. Thirty pregnant rats were divided into 5 groups as: Control, LPS (1 mg/kg), LPS + SLB (1 mg/kg), LPS + Mg (Dhaka protocol), LPS + SLB + Mg. Rats were sacrificed 4 h after LPS administration, then placental and fetal brain tissues were collected. LPS administration enhanced the levels of tumor necrosis factor-alpha, vascular endothelial growth factor, caspase-3 immunoexpressions, BAX, eukaryotic initiation factor 2-alpha, s100, and glial fibrillary acidic protein expressions and lowered BCL2 expressions in the placenta or fetal brains. SLB and Mg treatments were observed to reverse all these findings, and the most significant positive effect was in the LPS + SLB + Mg group. The known anti-inflammatory activity of Mg, when used with SLB, preventing the transition to apoptosis and increasing antioxidant enzyme activity, as identified in this study, can contribute significantly to the literature. However, these results need to be supported by additional molecular studies.

Assessment and comparative study of diosgenin doses in alleviating experimental periodontitis.

BACKGROUND: This study was performed to determine the therapeutic effects of diosgenin (DG) which is a steroidal saponin, administered at different doses on alveolar bone loss (ABL) in rats with experimental periodontitis using immunohistochemical and cone-beam computed tomography (CBCT). METHODS: Thirty-two male Wistar rats divided into four equal groups: control (non-ligated), periodontitis (P), DG-48, and DG-96. Sutures were placed at the gingival margin of the lower first molars to induce experimental periodontitis. Then, 48 and 96 mg/kg of DG was administered to the study groups by oral gavage for 29 days. At day 30, the animals were sacrificed and ABL was determined via CBCT. The expression patterns of osteocalcin (OCN), alkaline phosphatase (ALP), type I collagen (Col-1), B cell lymphoma 2 (Bcl 2), Bcl 2-associated X protein (Bax), bone morphogenetic protein 2 (BMP-2), and receptor activator of NF κB ligand (RANKL) were examined immunohistochemically. RESULTS: Histopathologic examination showed all features of the advanced lesion in the P group. DG use decreased all these pathologic changes. It was observed that periodontitis pathology decreased as the dose increased. DG treatment increased the ALP, OCN, Bcl 2, Col-1, and BMP-2 levels in a dose-dependent manner, compared with the P group (p < 0.05). DG decreased the expression of RANKL and Bax in a dose-dependent manner (p < 0.05). ABL was significantly lower in the DG-48 and DG-96 groups than in the P group (p < 0.05). CONCLUSION: Collectively, our findings suggest that DG administration protects rats from periodontal tissue damage with a dose-dependent manner, provides an increase in markers of bone formation, decreases in Bax/Bcl-2 ratio and osteoclast activation.

Cannabidiol ameliorates lipopolysaccharide-induced cardiovascular toxicity by its antioxidant and anti-inflammatory activity via regulating IL-6, Hif1α, STAT3, eNOS pathway.

BACKGROUND: Systemic inflammation causes several organ damage by activating the intracellular signaling mechanisms. Heart and aorta tissues are the structures mostly affected by this situation. By examining underlying processes, this study sought to determine whether cannabidiol (CBD) may have protective effects against the cardiovascular damage brought on by lipopolysaccharide (LPS). MATERIALS AND METHODS: A total of 32 female rats were randomly allocated to one of four groups: control, lipopolysaccharide (LPS) (5 mg/kg, i.p., single dose), LPS + CBD (5 mg/kg, i.p., single dose), and CBD groups. The rats were killed six hours after receiving LPS, and tissues from the heart and aorta were taken. Histopathological and immunohistochemical analyzes were performed. Oxidative stress was evaluated biochemically by spectrophotometric method. Expression levels of genes were studied by RT-qPCR method. RESULTS: Histopathological analysis of the LPS group showed moderate hyperemia, hemorrhages, edema, inflammation, and myocardial cell damage. There was a slight to moderate increase in Cox-1, G-CSF, and IL-3 immunoexpressions, along with enhanced expressions of IL-6, Hif1α, and STAT3 genes, and decreased expressions of eNOS genes. Additionally, there were increased levels of TOS and decreased TAS levels observed biochemically. CBD treatment effectively reversed and improved all of these observed changes. CONCLUSIONS: CBD protects the heart and aorta against systemic inflammation through its antioxidant and anti-inflammatory activity via regulating IL-6, Hif1α, STAT3, and eNOS intracellular pathways.

The prophylactic and therapeutic effects of cannabidiol on lung injury secondary to cardiac ischemia model in rats via PERK/NRF2/CHOP/BCL2 pathway.

BACKGROUND: Inflammation and oxidative stress are key players in lung injury stemming from cardiac ischemia (LISCI). Cannabidiol (CBD) demonstrates tissue-protective properties through its antioxidant, anti-inflammatory, and anti-apoptotic characteristics. This study aims to assess the preventive (p-CBD) and therapeutic (t-CBD) effects of CBD on LISCI. METHODS: Forty male Wistar Albino rats were divided into four groups: control (CON), LISCI, p-CBD, and t-CBD. The left anterior descending coronary artery was ligated for 30 min of ischemia followed by 30 min of reperfusion. Lung tissues were then extracted for histopathological, immunohistochemical, genetic, and biochemical analyses. RESULTS: Histopathologically, marked hyperemia, increased septal tissue thickness, and inflammatory cell infiltrations were observed in the lung tissues of the LISCI group. Spectrophotometrically, total oxidant status and oxidative stress index levels were elevated, while total antioxidant status levels were decreased. Immunohistochemically, expressions of cyclooxygenase-1 (COX1), granulocyte colony-stimulating factor (GCSF), interleukin-6 (IL6) were increased. In genetic analyses, PERK and CHOP expressions were increased, whereas Nuclear factor erythroid 2-related factor 2 (NRF2) and B-cell leukemia/lymphoma 2 protein (BCL2) expressions were decreased. These parameters were alleviated by both prophylactic and therapeutic CBD treatment protocols. CONCLUSION: In LISCI-induced damage, both endoplasmic reticulum and mitochondrial stress, along with oxidative and inflammatory markers, were triggered, resulting in lung cell damage. However, both p-CBD and t-CBD treatments effectively reversed these mechanisms, normalizing all histopathological, biochemical, and PCR parameters.

When to Consider Invasive Lymph Node Staging in Non-Small-Cell Lung Cancer? A Novel Scoring System Utilising Metabolic Parameters in 18F-FDG PET/CT.

OBJECTIVE: The maximum standardised uptake value (SUVmax) is a widely utilised metric in positron emission tomography/computed tomography for clinically staging non-small-cell lung cancer (NSCLC), yet the reliability of SUVmax remains controversial. We herein aimed to assess the effectiveness of semi-quantitative parameters, encompassing size, SUVmax, metabolic tumour volume (MTV), total lesion glycolysis (TLG) and heterogeneity factor (HF), in evaluating both primary tumours and lymph nodes (LNs) on positron emission tomography/computed tomography. A novel scoring system was devised to appraise the role of semi-quantitative parameters and visually evaluate LNs for nodal staging. MATERIALS AND METHODS: Patients with pathological NSCLC, diagnosed between 2014 and 2019 and clinically staged I-III, were enrolled in the study. Patient demographics, including age, sex, tumour location, diameter, tumour-node-metastasis stage, as well as SUVmax, MTV, TLG and HF parameters of primary tumours and LNs, were documented. RESULTS: The analysis comprised 319 patients and 963 LNs. Patients had a mean age of 61.62 years, with 91.5% being male. Adenocarcinoma exhibited a histological association with LN metastasis (P=0.043). The study findings revealed that tumour size, SUVmax, MTV, TLG and HF did not significantly affect the detection of LN metastasis. Conversely, non-squamous cell carcinoma, LNs exhibiting higher FDG levels than the liver, LN size, SUVmax, MTV and TLG were identified as risk factors (P<0.0001). The identified cut-off values were 1.05cm for LN size, 4.055 for SUVmax, 1.805cm3 for MTV and 5.485 for TLG. The scoring system incorporated these parameters, and visual assessment indicated that a score of ≥3 increased the risk of metastasis by 14.33 times. CONCLUSION: We devised a novel scoring system and demonstrated that LNs with a score of ≥3 in patients with NSCLC have a high likelihood of metastasis. This innovative scoring system can serve as a valuable tool to mitigate excessive and extreme measures in the assessment of invasive pathological staging.

Superior In Vivo Wound-Healing Activity of Biosynthesized Silver Nanoparticles with Nepeta cataria (Catnip) on Excision Wound Model in Rat.

Silver nanoparticles were biosynthesized with Nepeta cataria plant extract. It was determined that the synthesized Nc-AgNPs gave a strong absorbance peak at 438 nm wavelength in the UV-vis spectrophotometer. SEM and TEM analyses of Nc-AgNPs showed that the synthesized nanoparticles had a spherical morphology. Based on XRD analysis, the average crystallite size of Nc-AgNPs was calculated at 15.74 nm. At the same time, EDS spectrum analysis exhibited dominant emission energy at 3 keV, indicative of Nc-AgNPs. Nc-AgNPs showed an inhibition zone of 12 nm in gram-negative Escherichia coli, 10 nm in gram-positive Enterococcus faecalis, and 11 nm in Staphylococcus aureus. Nc-AgNPs showed high antioxidant properties, with 63% at 5000 µg/mL. The wound-healing properties of Nc-AgNPs were evaluated in vivo in wound models created in a total of 20 Wistar albino male rats, divided into four groups. After 10 days of treatment, the highest wound closure rate was seen in the Nc-AgNP + Vaseline (Group IV) treatment group, at 94%. It was observed that Nc-AgNP + Vaseline nanoformulation significantly increased wound healing, similar to Silverdin®, and Vaseline alone supported healing but did not result in complete closure. Histopathological examination revealed an increase in mature Type 1 collagen in Group IV and positive control (Group II), with better collagen maturation in vehicle control (Group III) compared to negative control (Group I). Immunohistochemical analysis showed complete epithelialization in Group IV and Group II, with distinct cytokeratin expressions, while Group III exhibited mild expressions.

Is resveratrol really effective in kidney disease?: A different perspective than ever before.

BACKGROUND: Chronic kidney disease (CKD) is a global health problem and it is stated that the use of resveratrol supplement contributes to the protection of kidney health. In this study, it was aimed to evaluate the effect of resveratrol supplementation on kidney function, inflammation and histopathological findings in rats with experimental adenine-induced kidney damage. METHODS: Three different groups of 10 randomly selected rats were formed. The first group was the negative control group, the second group was the uremic control group (KDG), and the third group was the group in which uremia was created and resveratrol was applied (RG). Kidney damage was induced by administration of 200 mg/kg adenine. Resveratrol supplementation was administered at 20 mg/kg after kidney damage. Serum urea, creatinine, indoxyl sulfate (IS), p-cresol, glomerular filtration rate, C-reactive protein (CRP); interleukin (IL)-6 and tumor necrosis factor (TNF)-α gene expression levels and histopathological findings were evaluated. RESULTS: It was determined that resveratrol supplement applied after the formation of connective tissue in renal failure didn't have an improvement effect on the urine amount, kidney function and inflammatory parameters and histopathological changes (p > 0.05). Just, the increase in the CRP value of KDG (p < 0.05) was not observed in RG. CONCLUSION: The findings suggest that resveratrol administered after kidney damage with adenine has no effect on kidney disease.

L-carnitine protects the lung from radiation-induced damage in rats via the AMPK/SIRT1/TGF-1ß pathway.

Radiotherapy (RAD) is a common cancer treatment method, but it can have unintended lung side effects. L-carnitine (LCAR) is an amino acid with antioxidant and anti-inflammatory properties. This study aims to demonstrate the effects of LCAR against radiation-induced acute lung injury and to elucidate its possible protective molecular mechanisms. A total of 32 Wistar albino rats were separated into four groups: control, RAD (10 Gy once on 1st day), RAD + LCAR (intraperitoneally, 200 mg/kg/d, for 10 days), and LCAR. At the end of the experiment, the rats were euthanized, and the lung tissues were collected for histopathological, immunohistochemical, biochemical, and genetic analysis. Emphysema, pronounced hyperemia, increased total oxidant status, and increased caspase-3 and TNF-α immunostainings were all seen in the lung tissues of the RAD group. LCAR treatment reduced these negative effects. In addition, AMPK and SIRT1 gene expressions increased in the RAD + LCAR group compared to the RAD group, while TGF-1ß gene expression decreased. While RAD caused major damage to the lungs of rats, LCAR application reduced this damage through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. Specifically, LCAR reduced fibrosis while attenuating RAD-induced inflammation and oxidative stress via the AMPK/SIRT1/TGF-1ß pathway. Therefore, LCAR can be considered a supplement to reduce complications associated with RAD.

Efficacy of fennel (Foeniculum vulgare) and anise (Pimpinella anisum) essential oils as anaesthesics in common carp (Cyprinus carpio L. 1758).

In this study, the anaesthetic effects of fennel and anise essential oils were investigated on common carp. Fish (10 ± 0.45 g) were exposed to nine concentrations of essential oils (5, 10, 20, 50, 100, 200, 300, 400 and 500 mg L-1). Additionally, the histopathological effects on the fish tissues including gill, skin and hepatopancreas and physiological effects on some blood parameters (Na+, K+, Ca+2, Cl-, total plasma protein and glucose) of essential oils were investigated in carp. At the end of the experiment, fennel oil showed an anaesthetic effect at a concentration of 500 mg L-1 in carp (anaesthesia induction and recovery times were 308 and 472 s, respectively). Anise essential oil showed deep anaesthesia at a concentration of 100 mg L-1, but anaesthesia induction time was found to be very long (20 min). In addition, anise oil at concentrations above 100 mg L-1 caused 10% mortality in fish. Blood parameters except glucose level in both essential oils were unchanged during deep anaesthesia in carp. However, plasma glucose levels were found lower in fish anaesthetized with anise oil than control and fennel groups (P < 0.05). At the histopathological examination, no pathological findings were observed in any organ of fish in the fennel group. However, severe hyperemia and inflammatory cell infiltrations in gills, erosive lesions in the skin and slight inflammatory reactions in the skin were observed in the anise group. The present study demonstrated that fennel essential oil at 500 mg L-1 concentration can be used as an effective and safe anaesthetic in common carp, but anise essential oil is not suitable.

Serum testosterone levels and oxidative stress in type 1 diabetes, type 2 diabetes, and obesity.

INTRODUCTION: Obesity, type 1 diabetes mellitus (T1DM), and type 2 diabetes mellitus (T2DM) are metabolic diseases that continue to be a global problem. Testosterone levels in men are affected by several factors, including obesity and DM. Although the relationship between diabetes and testosterone is not fully understood, oxidative stress is thought to play a major role. The aim of this study was to compare serum testosterone levels and oxidative stress markers [total antioxidant status (TAS), total oxidant capacity (TOS), oxidative stress index (OSI), and ischaemic modified albumin (IMA)] among the control group and experimentally induced obese, T1DM, and T2DM rats. MATERIAL AND METHODS: The study included 28 male Sprague-Dawley rats divided into 4 groups: the obesity group were fed a high-fat diet (HFD), the T2DM group received a HFD plus a single dose of streptozocin (STZ), the T1DM group received only STZ, and there was a control group. Serum testosterone, TAS, TOS, OSI, and IMA were analysed. RESULTS: Serum testosterone levels were lower in the T1DM and T2DM groups compared to the control and obesity groups. The TOS levels were highest in the T2DM group, followed by the T1DM group, the obesity group, and finally the control group. No significant difference was found between the obesity group and the control group in terms of TOS levels. Regarding TAS levels, the order observed was control group > obesity group > T2DM > T1DM. Testosterone was positively correlated with TAS and negatively correlated with TOS and OSI. CONCLUSIONS: Increased oxidative stress in diabetes may be an important factor that decreases serum testosterone levels.

A novel insight into the neuroprotective effects of cannabidiol: maintained apelin/dopamine synthesis, NRF2 signaling, and AKT/CREB/BDNF gene expressions.

Neuroinflammation is a process associated with degeneration and loss of neurons in different parts of the brain. The most important damage mechanisms in its formation are oxidative stress and inflammation. This study aimed to investigate the protective effects of cannabidiol (CBD) against neuroinflammation through various mechanisms. Thirty­two female rats were randomly divided into 4 groups as control, lipopolysaccharide (LPS), LPS + CBD and CBD groups. After six hours following LPS administration, rats were sacrificed, brain and cerebellum tissues were obtained. Tissues were stained with hematoxylin­eosin for histopathological analysis. Apelin and tyrosine hydroxylase synthesis were determined immunohistochemically. Total oxidant status and total antioxidant status levels were measured, and an oxidative stress index was calculated. Protein kinase B (AKT), brain-derived neurotrophic factor (BDNF), cyclic­AMP response element­binding protein (CREB) and nuclear factor erythroid 2­related factor 2 (NRF2) mRNA expression levels were also determined. In the LPS group, hyperemia, degeneration, loss of neurons and gliosis were seen in all three tissues. Additionally, Purkinje cell loss in the cerebellum, as well as neuronal loss in the cerebral cortex and hippocampus, were found throughout the LPS group. The expressions of AKT, BDNF, CREB and NRF2, apelin and tyrosine hydroxylase synthesis all decreased significantly. CBD treatment reversed these changes and ameliorated oxidative stress parameters. CBD showed protective effects against neuroinflammation via regulating AKT, CREB, BDNF expressions, NRF2 signaling, apelin and tyrosine hydroxylase synthesis.

Inulin protects against the harmful effects of dietary emulsifiers on mice gut microbiome.

Background: The prevalence of inflammatory bowel diseases is increasing, especially in developing countries, with adoption of Western-style diet. This study aimed to investigate the effects of two emulsifiers including lecithin and carboxymethyl cellulose (CMC) on the gut microbiota, intestinal inflammation and the potential of inulin as a means to protect against the harmful effects of emulsifiers. Methods: In this study, male C57Bl/6 mice were divided into five groups (n:6/group) (control, CMC, lecithin, CMC+inulin, and lecithin+inulin). Lecithin and CMC were diluted in drinking water (1% w/v) and inulin was administered daily at 5 g/kg for 12 weeks. Histological examination of the ileum and colon, serum IL-10, IL-6, and fecal lipocalin-2 levels were analyzed. 16S rRNA gene V3-V4 region amplicon sequencing was performed on stool samples. Results: In the CMC and lecithin groups, shortening of the villus and a decrease in goblet cells were observed in the ileum and colon, whereas inulin reversed this effect. The lipocalin level, which was 9.7 ± 3.29 ng in the CMC group, decreased to 4.1 ± 2.98 ng with the administration of inulin. Bifidobacteria and Akkermansia were lower in the CMC group than the control, while they were higher in the CMC+inulin group. In conclusion, emulsifiers affect intestinal health negatively by disrupting the epithelial integrity and altering the composition of the microbiota. Inulin is protective on their harmful effects. In addition, it was found that CMC was more detrimental to microbiota composition than lecithin.

Nebivolol protects the liver against lipopolysaccharide-induced oxidative stress, inflammation, and endoplasmic reticulum-related apoptosis through Chop and Bip/GRP78 signaling.

This study aimed to examine the protective role of nebivolol (NEB) on liver tissue against the lipopolysaccharide (LPS)-induced sepsis model in rats by targeting endoplasmic reticulum (ER) stress-related binding immunoglobulin protein (Bip), CCAAT-enhancer-binding protein homologous protein (Chop) signaling pathways. Four groups, each comprising eight rats, were established: control, LPS, LPS + NEB, and NEB. Biochemical analyses included total oxidant status (TOS), serum aspartate transaminase (AST), and alanine aminotransferase (ALT) levels. Additionally, genetic assessments involved Chop and Bip/GRP78 mRNA expression levels, while histopathological examinations were conducted. Immunohistochemistry was used to determine interleukin-1 beta (IL-1 ß) and caspase-3 levels. The LPS group exhibited significantly higher AST, ALT, oxidative stress index, and TOS levels compared to the control group. Moreover, the LPS group demonstrated markedly increased Chop and Bip/GRP78 mRNA expression compared to the control group. Immunohistochemical analysis of the LPS group revealed significant upregulation in IL-1ß and caspase-3 expressions compared to the control group. Additionally, the LPS group showed significant hyperemia, mild hemorrhage, and inflammatory cell infiltrations. Comparatively, the LPS+NEB group exhibited a reversal of these alterations when compared to the LPS group. Collectively, our findings, suggest that NEB holds promise as a treatment in conditions where oxidative damage, inflammation, and ER stress-related apoptosis play significant roles in the pathogenesis.