The protective effect of Cloprostenol on ischemia/reperfusion injury in rat ovary: Histopathologic and immunohistochemically evaluation: An experimental study.

OBJECTiVES: This study investigates whether Cloprostenol, a synthetic prostaglandin analog, could protect against ischemia/reperfusion (IR) injury in rat ovaries. METHODS: Adult female rats were divided into four groups: Sham groups, ischemia (IS) groups, ischemia/reperfusion (IR) groups, and Cloprostenol-treated (CT) groups. The IR injury model was established by clamping the ovarian pedicle for a specified period, followed by reperfusion. The CT group received a pre-treatment of Cloprostenol before inducing ischemia. Ovarian tissues were collected for histological, and immunohistochemical examination. RESULTS: The IS group exhibited severe morphological damage to ovarian tissues, including disrupted tissue architecture and increased apoptosis (p < 0.001). In contrast, the CT group displayed significantly improved ovarian histology, with notable preservation of ovarian tissue and reduced apoptotic activity (p < 0.01). Immunohistochemical analysis revealed that the levels of 8-Hydroxy-2-deoxyguanosine (8-OHdG), Caspase 3, Cyclooxygenase 2 (COX-2), and Interleukin 1 beta (IL-1ß) staining, which were elevated in the IS and IR groups, were significantly diminished in the CT group (p < 0.05). CONCLUSiON: Cloprostenol administration before IR injury in rat ovaries demonstrated a remarkable protective effect by improving histological damage and reducing DNA damage inflammation. These results highlight the therapeutic potential of Cloprostenol in safeguarding ovarian health against IR.

Exploring altered free amino acids and metabolites: Insights into the metabolic landscape of preeclampsia.

INTRODUCTION: Preeclampsia (PE) is a complex disease that poses a risk for maternal and perinatal morbidity and mortality. This study aimed to investigate the role of maternal serum amino acids (AAs) levels in PE. MATERIALS AND METHODS: A total of 56 pregnant women (26 with PE and 30 controls) were included in the study. The participants had a confirmed gestational age between 24 and 37 weeks. The mean body mass index (BMI) for the PE group was 33.1 kg/m2, while the control group had a mean BMI of 29.6 kg/m2. AAs levels were quantified, and statistical analyses were performed to identify significant differences between the two groups. Receiver Operating Characteristic (ROC) curve analysis was employed the diagnostic potential of specific AAs. RESULTS: We observed significantly elevated levels of multiple AAs in the PE group, including citrulline, lysine, ethanolamine, ornithine and histidine. Citrulline exhibited exceptional predictive power for PE with 100.0% sensitivity and specificity at a cutoff of 7.79 µmol/L, reflected in an area under the curve (AUC) of 1.000. DISCUSSION: Our study highlights the crucial involvement of altered amino acid levels, specifically in the urea cycle, disruptions in lysine and ethanolamine metabolism in PE development. Exploring these changes may reveal new therapeutic targets, providing insights into the disease's molecular mechanisms. Understanding amino acid metabolism in PE not only informs therapeutic strategies but also holds the potential to revolutionize early diagnosis and intervention.

Exploring free amino acid profiles in Crimean-Congo hemorrhagic fever patients: Implications for disease progression.

This study investigated the intricate interplay between Crimean-Congo hemorrhagic fever virus infection and alterations in amino acid metabolism. The primary aim is to elucidate the impact of Crimean-Congo hemorrhagic fever (CCHF) on specific amino acid concentrations and identify potential metabolic markers associated with viral infection. One hundred ninety individuals participated in this study, comprising 115 CCHF patients, 30 CCHF negative patients, and 45 healthy controls. Liquid chromatography-tandem mass spectrometry techniques were employed to quantify amino acid concentrations. The amino acid metabolic profiles in CCHF patients exhibit substantial distinctions from those in the control group. Patients highlight distinct metabolic reprogramming, notably characterized by arginine, histidine, taurine, glutamic acid, and glutamine metabolism shifts. These changes have been associated with the underlying molecular mechanisms of the disease. Exploring novel therapeutic and diagnostic strategies addressing specific amino acids may offer potential means to mitigate the severity of the disease.

Exploring free amino acid profiles in CCHF patients: Implications for disease progression.

This study investigated the intricate interplay between Crimean-Congo hemorrhagic fever virus (CCHFV) infection and alterations in amino acid metabolism. Our primary aim is to elucidate the impact of Crimean-Congo hemorrhagic fever (CCHF) on specific amino acid concentrations and identify potential metabolic markers associated with viral infection. One hundred ninety individuals participated in this study, comprising 115 CCHF patients, 30 CCHF negative patients, and 45 healthy controls. Liquid chromatography-tandem mass spectrometry techniques were employed to quantify amino acid concentrations. The amino acid metabolic profiles in CCHF patients exhibit substantial distinctions from those in the control group. Patients highlight distinct metabolic reprogramming, notably characterized by arginine, histidine, taurine, glutamic acid, and glutamine metabolism shifts. These changes have been associated with the underlying molecular mechanisms of the disease. Exploring novel therapeutic and diagnostic strategies addressing specific amino acids may offer potential means to mitigate the severity of the disease.

Analysis of liver fibrosis equations as a potential role of predictive models in Crimean-Congo hemorrhagic fever.

Crimean-Congo Hemorrhagic Fever (CCHF) is a formidable global health concern, characterized by its rapid onset and high fatality rate. Distinguishing between patients at different stages remains challenging because of overlapping clinical features. This study aimed to evaluate the diagnostic efficacy of 14 hepatic fibrosis indices for distinguishing fatal cases and intensive care unit requirement (ICU) in CCHF. This study enrolled 194 patients with confirmed CCHF. Laboratory measurements were performed using auto analyzers. Indirect indicators of fibrosis were calculated for each patient based on previously described formulas. Time-dependent receiver operating characteristic (tdROC) curve analyses were employed to evaluate the predictive effects of hepatic fibrosis indices on both intensive care unit requirement and overall survival among patients. Regarding the tdROC analyses results, the highest area under the curve statistics were obtained for the baseline S-INDEX, KING, and GPRI scores (0.920, 0.913, and 0.909 respectively) in the estimation of ten-day survival, and the baseline KING, Goteborg University cirrhosis index (GUCI), and gamma-glutamyl transferase to platelet ratio index (GPRI) scores (0.783, 0.773, and 0.769 respectively) in the estimation of intensive care requirements for up to ten days. S-index and KING index emerged as early predictors of ten-day survival, while KING, GUCI, and GPRI indices demonstrated predictive capabilities for ICU admission on the first day. The identified indices have the potential to assist healthcare providers in making timely and informed decisions regarding patient management and treatment strategies. Further research and validation are warranted to solidify the role of these hepatic fibrosis indices in the clinical setting and enhance their broader applicability in the management of CCHF.

Dysregulated Leukotriene Metabolism in Patients with COVID-19.

This study aimed to examine the leukotriene metabolism during COVID-19. In total, 180 participants were included in this study, of which 60 were healthy controls, 60 required intensive care units (ICU), and 60 did not require intensive care (non-ICU). The serum levels of 5-lipoxygenase (5-LO), 5-LO activating protein (ALOX5AP), and cysteinyl leukotriene (CYSLT) were measured, and the mRNA expression levels of 5-LO, ALOX5AP, and cysteinyl leukotriene receptor 1 (CYSLTR1) were investigated. Compared with the control group, both the non-ICU and ICU groups had lower levels of 5-LO and mRNA expression. ICU patients had lower levels of 5-LO and mRNA expression than non-ICU patients. CYSLTR1 mRNA expression was highest in the ICU group, followed by the non-ICU group, and healthy controls had the lowest mRNA expression levels. CYSLT levels were higher in the control group than in the non-ICU and ICU groups. CYSLTR1 expression was higher in patients than in controls; therefore, selective leukotriene receptor blockers can be used as treatment options. CYSLTR1 expression was higher in the ICU group than in the non-ICU group. Furthermore, CYSLTR1 mRNA expression may be a promising biomarker of COVID-19 severity.

Maternal serum amino acid levels as predictors of premature rupture of membranes: A comprehensive analysis.

INTRODUCTION: The aim of this study is to investigate the association between altered maternal serum amino acids (AAs) levels and premature rupture of membranes (pPROM) in pregnant women. METHODS: We conducted a case-control study involving 60 pregnant women diagnosed with pPROM and 60 healthy pregnant women as controls. Amino acid levels were quantified using high-performance liquid chromatography. Receiver operating characteristic (ROC) curve analysis was performed to determine the predictive capability of specific AAs for pPROM. RESULTS: Our findings revealed that lysine, glycine, and glutamic acid levels were significantly elevated in the pPROM group compared with the control group. Lysine, with a threshold value exceeding 137.90 µmol/L, exhibited the highest predictive accuracy, with an area under the curve (AUC) of 0.796 (p < 0.001), sensitivity of 66.7 %, and specificity of 80.0 %. Glycine, with a cut-off value of >242.48 µmol/L, had an AUC of 0.789 (p < 0.001), sensitivity of 83.3 %, and specificity of 65.0 %. Glutamic acid, at a threshold of 111.40 µmol/L, demonstrated an AUC of 0.787 (p < 0.001), sensitivity of 88.3 %, and specificity of 65.0 %. These AAs could effectively predict the occurrence of pPROM. CONCLUSION: Elevated blood levels of lysine, glycine, and glutamic acid were found to be associated with pPROM. These AAs serve as potential predictive biomarkers for pPROM, with lysine showing the highest AUC and sensitivity. Identifying such biomarkers may contribute to the development of non-invasive diagnostic tools for pPROM risk assessment, enabling timely interventions and improved maternal and fetal outcomes.

Relationship between blood calcium level and post-milking teat canal closure in dairy cows.

The teat canal-one of the primary defense mechanisms of the udder-ensures the milk flow during milking in bovines and prevents pathogens from entering the udder by forming a barrier through the elastic muscle and keratin layers tightly closing the surrounding area. The current study investigated the effects of blood calcium status on teat closure in cows after milking. The study covered 200 healthy teats, of which 100 were from normocalcemic (NC) cows and 100 were from subclinical hypocalcemic (SCH) cows. Teat canal length (TCL) and width (TCW) were measured with ultrasonography at 0-min pre-milking and 15- and 30-min post-milking. Cylindrically shaped teat canal volume (TCV) was calculated by deriving from TCL and TCW. Time-dependent changes in teat canal closure and their relationships with blood calcium levels were analyzed. The results showed that the calcium level did not affect TCL, TCW, and TCV (P > 0.05) during the 15-min post-milking period. However, TCL (P < 0.001), TCW (P < 0.05), and TCV (P < 0.001) were lower in NC cows than in SCH cows at 30-min post-milking. At 15-min post-milking, no correlation existed between the teat canal closure (ΔTCL, ΔTCW, and ΔTCV) and the blood calcium level, while significant correlations were available between the teat canal closure and the blood calcium level {ΔTCL (r: - 0.288, P < 0.001), ΔTCW (r: - 0.260, P < 0.001), ΔTCV (r: - 0.150, P < 0.05)} at 30-min post-milking. The current study concluded that the blood calcium status significantly impacts the teat canal closure in bovines, and calcium status should be meticulously monitored with the mastitis control program to apply necessary strategic steps.

Validation of low-density lipoprotein cholesterol equations in pediatric population.

Several studies have shown a high prevalence of dyslipidemia in children. Since childhood lipid concentrations continue into adulthood, recognition of lipid abnormalities in the early period is crucial to prevent the development of future coronary heart disease (CHD). Low density lipoprotein cholesterol (LDL-C) is one of the most used parameters in the initiation and follow-up of treatment in patients with dyslipidemia. It is a well known fact that LDL-C lowering therapy reduces the risk of future CHD. Therefore, accurate determination of the LDL-C levels is so important for the management of lipid abnormalities. This study aimed to validate different LDL-C estimating equations in the Turkish population, composed of children and adolescents. A total of 3,908 children below 18 years old at Sivas Cumhuriyet University Hospital (Sivas, Turkey) were included in this study. LDL-C was directly measured by direct homogeneous assays, i.e., Roche, Beckman, Siemens and estimated by Friedewald's, Martin/Hopkins', extended Martin-Hopkins' and Sampson's formulas. The concordances between the estimations obtained by the formulas and the direct measurements were evaluated both overall and separately for the LDL-C, triglycerides (TG) and non-high-density lipoprotein cholesterol (non-HDL-C) sublevels. Linear regression analysis was performed and residual error plots were generated between each estimation and direct measurement method. Coefficient of determination (R 2) and mean absolute deviations were also evaluated. The overall concordance of Friedewald, Sampson, Martin-Hopkins and the extended Martin-Hopkins formula were 64.6%, 69.9%, 69.4%, and 84.3% for the Roche direct assay, 69.8%, 71.6%, 73.6% and 80.4% for the Siemens direct assay, 66.5%, 68.8%, 68.9% and 82.1% for the Beckman direct assay, respectively. The extended Martin-Hopkins formula had the highest concordance coefficient in both overall and all sublevels of LDL-C, non-HDL-C, and TG. When estimating the LDL-C categories, the highest underestimation degrees were obtained with the Friedewald formula. Our analysis, conducted in a large pediatric population, showed that the extended Martin-Hopkins equation gives more reliable results in estimation of LDL-C compared to other equations.

Protective and Therapeutic Effects of Bovine Amniotic Fluids Collected in Different Trimesters on the Epidural Fibrosis After Experimental Laminectomy in Rats.

BACKGROUND: The aim of this study was to investigate the protective and therapeutic effects of bovine amniotic fluid (BAF) on the inhibition of epidural fibrosis (EF) after experimental laminectomy. METHODS: Forty female Sprague Dawley rats were used. The amniotic fluids were collected from each trimester of a pregnant cow. The rats were divided into 5 groups. Whereas no laminectomy was applied to the control group, animals in the sham group underwent laminectomy. Laminectomy was performed in the animals in other groups and the operation area was closed by dripping 1 mL of BAF collected in 3 trimesters of pregnancy. Animals were killed 28 days after the operation. RESULTS: Compared with control, VEGF gene expression levels were downregulated approximately 5-fold in BAF-2. Whereas IL-6 was upregulated approximately 8-fold in the sham, it was downregulated 5-fold and 3-fold in BAF-1 and BAF-2, respectively. There was downregulation in BAF-2 and BAF-3 in terms of CD105 gene expression levels. TGFß1 was upregulated approximately 2-fold in the sham group and downregulated in BAF-1 and BAF-2. Although histopathologic alterations including EF grade and fibroblast cell density were found to increase in the sham group, all BAF treatment decreased those of alterations. The highest CD105 immunoreactivity was detected in the sham group. All BAF treatment markedly aggravated fibrosis via decreasing CD105 immunoreactivity. In terms of grading parameters, almost the closest grades to the control were determined in the BAF-2. BAF collected in the second trimester is most effective in healing of scar tissue and preventing fibrosis via decreasing microvessel and fibroblast densities. CONCLUSIONS: The results indicate that BAF may be used as a potential protective agent to prevent EF.

Assessment of semaphorin 3A and semaphorin 7A levels in primary Sjogren's syndrome.

Sjogren's syndrome (SS) is a chronic autoimmune connective tissue disease. Varying rates of system involvements may be seen in the course of the disease. Semaphorins has multifunctions in several physiological and pathological processes such as immune system regulation. The association of Semaphorin 3A (Sema3A) and Semaphorin 7A (Sema7A), which are immune semaphorins, with autoimmune diseases is interesting for researchers. We aimed to compare serum Sema3A and Sema7A levels between primary SS and control subjects, and investigated Sema3A and Sema7A levels in disease subgroups and associated system involvements. 50 consecutive primary SS patients and 40 healthy subjects followed in the Rheumatology clinic of Cumhuriyet University Medical Faculty between 2017 and 2018 were included in the study. Inclusion criteria of patients were diagnosis of primary SS according to the 2016 ACR/EULAR classification criteria. Serum Sema3A and Sema7A levels were measured by commercial ELISA kit. Both groups were similar in terms of age, gender, and body mass index. Serum Sema3A and Sema7A levels were significantly lower in SS than in the controls (p = 0.001 and p = 0.005, respectively). Serum Sema3A levels were significantly lower in patients with renal involvement than in patients without (p = 0.03). Sema3A and Sema7A may play a role in the etiopathogenesis of SS and may be a potential serological marker for the diagnosis of SS and may be a target for treatment.

Pulsed-wave Doppler ultrasonographical measurements of supra-mammary lymph nodes for diagnosis of bovine mastitis.

The aim of this study was to investigate the relationship between mastitis and supra-mammary lymph nodes in lactating cows in terms of Pulsed-wave (PW) Doppler ultrasonographical measurements. A total of 102 head cows in lactation period were divided into three groups. The cows in which all mammary lobes were California mastitis test (CMT)-negative (n = 27) formed the 1st group; those with CMT-positive mammary lobe (n = 43) formed the 2nd group and the cows with clinical mastitis in at least one mammary lobe (n = 32) formed the 3rd group. In PW Doppler ultrasonography, end-diastolic velocity, systolic peak velocity and time-averaged maximum velocity were measured at the most prominent artery of the lymph node. A quantitative scaling was performed by determining the pulsatile index and resistance index scales based on blood flow parameters. There was no statistically significant difference between the study groups in terms of PW Doppler ultrasonographical measurements of supra-mammary lymph nodes. In conclusion, the use of PW Doppler ultrasonographic data of the supra-mammary lymph nodes will not provide useful information about the current condition of mastitis in cows.

Post-mating diclofenac vs. carprofen treatment on serum progesterone levels and reproductive outcomes in Hungarian-Merino ewes during the non-breeding season.

The maternal recognition process is crucial for the establishment of healthy pregnancy. In this process, anti-luteolytic applications are one of the main reproductive strategies to manage the embryonic losses and maximize reproductive profitability in farm animals. The aim of this study was to investigate the efficacy of post-mating NSAID treatments on reproductive parameters (pregnancy rate, lambing rate, multiple birth rate, litter size) and serum progesterone levels in ewes stimulated with progesterone non-breeding season. For this purpose, two different experiments (diclofenac and carprofen) were conducted in the same ewe flock induced with short-term progestogen-based protocol in the non-breeding season for two consecutive years. In experiment 1 (n = 85), 42 ewes were injected with 2.5 mg/kg diclofenac on the 9th and 10th days post-mating, and the rest were not treated and served as control. In experiment 2 (n = 82), 40 ewes were injected with 1.4 mg/kg carprofen on the 9th days post-mating, and the rest were not treated as control. In both experiments, blood samples were collected from all ewes on days 9, 12 and 13 post-mating to measure serum progesterone levels. In both experiments, there were no differences both reproductive parameters and serum progesterone levels when compared to the control groups. It was concluded that post-mating diclofenac and carprofen treatments in the critical period have no significant effects on both reproductive parameters and serum progesterone levels in ewes in the non-breeding season.

Mitochondrial Homeostasis and Mast Cells in Experimental Hepatic Ischemia-Reperfusion Injury of Rats.

BACKGROUND: Ischemia-reperfusion injury is a histopathological event and is an important cause of morbidity and mortality after hepatobiliary surgery. We aimed to investigate the protective effect of uridine on hepatic ischemia-reperfusion injury in rats. METHODS: The animals were divided into 4 groups (n = 8): group I (control), group II: ischemia-reperfusion (30 minutes ischemia and 120 minutes reperfusion), group III: ischemia-reperfusion+uridine (at the beginning of reperfusion), and group IV: ischemia-reperfusion+uridine (5 minutes before ischemia-reperfusion). Uridine was administered a single dose of 30 mg/kg IV. The 3 elements of the hepatoduodenal ligament (hepatic artery, portal vein, and biliary tract) were obliterated for 30 minutes. Then hepatic reperfusion was achieved for 120 minutes. RESULTS: In the ischemia-reperfusion group, both liver tissues and serum chymase activity and high-temperature requirement A2 levels were higher. Severe central vein dilatation and congestion, widening sinusoidal range, diffuse necrotic hepatocytes and dense erythrocyte accumulation in sinusoids, and strongly inducible nitric oxide synthase expression were seen in the ischemia-reperfusion group. A clear improvement was seen in both uridine co-administration and pretreatment groups. CONCLUSION: Our results revealed that uridine limits the development of liver damage under conditions of ischemia-reperfusion, thus contributing to an increase in hepatocyte viability.

Metabolomic profiling in ankylosing spondylitis using time-of-flight mass spectrometry.

BACKGROUND & AIMS: Ankylosing spondylitis (AS) is an inflammatory disease associated with destructive changes in the skeleton and joints. The exact molecular mechanism of the disease has not been fully elucidated. This study aimed to determine metabolic differences between active AS patients and healthy controls to understand the molecular mechanism of AS. PATIENTS AND METHODS: The study included 38 subjects, comprising 18 patients with active AS and 20 healthy controls. Metabolic profiling of the plasma was performed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC Q-TOF/MS). Data acquisition, classification, and identification were achieved with the METLIN (https://metlin.scripps.edu/) database and XCMS (https://xcmsonline.scripps.edu). RESULTS: Significant alterations were identified in the unsaturated fatty acids (FA), linoleic acid, alpha-linolenic acid, FA degradation, and FA biosynthesis pathways. Down -regulations were observed in phosphatidylcholine (PC) (16:0/0:0), beta-d-Fructose, stearic acid, trimipramine N-Oxide and muconic acid, and up-regulation were detected in PC (18:2/0:0), 3-Methylindole, palmitic acid (PA), alpha-Tocotrienol, and beta-d-glucopyranoside in active AS patients compared to the healthy control subjects. CONCLUSION: Pathway analysis revealed that dysregulation in FA metabolism is associated with AS, and therefore, modulation of diet according to PA and PC may be potential therapeutic targets.

Validation of Friedewald, Martin-Hopkins and Sampson low-density lipoprotein cholesterol equations.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is an important biomarker for determining cardiovascular risk and regulating lipid lowering therapy. Therefore, the accurate estimation of LDL-C concentration is essential in cardiovascular disease diagnosis and prognosis. Sampson recently proposed a new formula for the estimation of LDL-C. However, little is known regarding the validation of this formula. OBJECTIVES: This study aimed to validate this new formula with other well-known formulas in Turkish population, composed of adults. METHODS: A total of 88,943 participants above 18 years old at Sivas Cumhuriyet University Hospital (Sivas, Turkey) were included to this study. LDL-C was directly measured by homogeneous assays, i.e., Roche, Beckman and Siemens and estimated by Friedewald's, Martin-Hopkins', extended Martin-Hopkins' and Sampson's formulas. The concordances between the estimations obtained by the formulas and the direct measurements were evaluated both in general and separately for the LDL-C, TG and non-HDL-C sublevels. Linear regression analysis was applied and residual error plots were generated between each estimation and direct measurement method. Coefficient of determination (R2) and mean absolute deviations were also calculated. RESULTS: The results showed that the extended Martin-Hopkins approach provided the most concordant results with the direct assays for LDL-C estimation. The results also showed that the highest concordances were obtained between the direct assays with the extended Martin-Hopkins formula calculated with the median statistics obtained from our own population. On the other hand, it was observed that the results of the methods may differ in different assays. The extended Martin-Hopkins approach, calculated from the median statistics of our population, gave the most concordant results in patients with "low LDL-C level (LDL-C levels < 70 mg/dL) or hypertriglyceridemia (TG levels ≥ 400 mg/dL)". CONCLUSIONS: Although the results of the formulas in different assays may vary, the extended Martin-Hopkins approach was the best one with the highest overall concordances. The validity of the Martin Hopkins' and Sampson's formulas has to be further investigated in different populations.

Dose related inhibitor effect of enrofloxacin on in vitro feline spontaneous myometrial contractility.

Enrofloxacin is one of the most widely used antibacterial drugs in feline medicine. This study investigated the effects of enrofloxacin on in vitro feline spontaneous myometrial contractility at different sexual stages. Uterine samples of the 20 queen cats at different sexual periods were placed in a tissue bath, and in vitro spontaneous stretch-induced myometrial contractions were recorded for 10 min. The tissue bath was adjusted for cumulative enrofloxacin concentrations of 0.25 mM, 0.50 mM, 1.00 mM, and 2.00 mM, respectively. Myometrial contractions were recorded for 10 min after each dose was adjusted in the tissue bath. It was observed that enrofloxacin caused a significant decrease in the peak amplitude and area under curve, while causing an increase the frequency of stretch-induced myometrial contractions in a dose dependent manner in vitro at all sexual stages. The current preliminary study concluded that enrofloxacin has an inhibitory effect on in vitro feline uterine myometrial activity at all sexual stages. It is recommended to take this medical effect into consideration and apply enrofloxacin and uterotonics together in treatment of uterine infections in feline medicine.

A novel therapeutic approach to NASH: Both polyethylene glycol 3350 and lactulose reduce hepatic inflammation in C57BL/6J mice.

BACKGROUND: The gut-liver axis is one of the most emphasized topics in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Intestinal microbiota dysbiosis has been shown to be a predictor of disease severity and progression to fatty liver disease. Therefore, research addressing gut-based therapies has become popular. OBJECTIVES: To investigate the effect of lactulose and polyethylene glycol 3350 (PEG 3350) in mice with induced obesity and NAFLD at a non-diarrheal dose. MATERIAL AND METHODS: Thirty-six C57BL/6J male mice were divided into 6 groups. The first 2 groups (n = 6 each) were used as an induced obesity model (group A) and NAFLD model (group B) for 8 weeks. The remaining 24 animals were categorized into control diet group, high-fat diet (HFD) group, HFD + lactulose group, and HFD + PEG 3350 group. Serum and liver tissue samples were obtained for biochemical and histopathological analyses, respectively. RESULTS: The HFD + lactulose treatment group displayed a significant decrease in liver weight (1.3 (1.3-1.4) kg compared to 1.8 (1.6-1.9) kg) and NAFLD activity score (NAS) (1.5 (1.0-3.0) compared to 5.0 (4.0-5.0), respectively; p = 0.0043, p = 0.0021) when compared with the HFD group. However, a decrease in body weight (35.0 (34.6-36.0) kg compared to 40.9 (34.7-41.9) kg) and hepatosteatosis (HS) rate (33.3% compared to 100.0%) were not statistically significant (p = 0.1796, p = 0.0606, respectively). The HFD + PEG 3350 treatment group showed a statistically significant decrease in body weight (32.4 (30.2-33.9) kg compared to 40.9 (34.7-41.9) kg), liver weight (1.5 (1.3-1.5) kg compared to 1.8 (1.6-1.9) kg), HS rate (16.7% compared to 100.0%) and NAS (0.5 (0.0-1.0) compared to 5.0 (4.0-5.0); p = 0.0086, p = 0.0086, p = 0.0151, and p = 0.0021, respectively) when compared with the HFD group. CONCLUSIONS: We demonstrated that non-diarrheal dose of lactulose and PEG 3350 reduced hepatic inflammation in mice with induced NAFLD. It was also observed that PEG 3350 decreased HS and body weight. We believe these mechanisms can be utilized as novel therapeutic approaches in NAFLD in prospective human studies.

Different threshold levels of circulating total and free 25-hydroxyvitamin D for the diagnosis of vitamin D deficiency in obese adolescents.

The total serum 25-hydroxyvitamin D [25(OH)DT] level is lower in obese individuals than in their nonobese peers, despite similar bone turnover markers and bone mineral density. This study aimed to investigate whether the threshold level of 25(OH)D for the diagnosis of vitamin D deficiency (VDD) in obese adolescents was lower than that in controls and to compare 25(OH)DT, free [25(OH)DF] and bioavailable [25(OH)DB] vitamin D with VDBP levels in obese individuals and their controls. A total of 173 adolescents (90 obese individuals and 83 controls) aged 12-18 years were included in the study. The metabolic and anthropometric parameters of the participants were recorded, the 25(OH)DT, 25(OH)DF, and VDBP levels were measured, and the 25(OH)DB levels were calculated. The cutoff values for VDD were estimated according to the level of 25(OH)D below which parathyroid hormone begins to rise. The obese subjects had lower 25(OH)DT (12.1 ± 5.8 vs. 16.4 ± 9.3 ng/mL, p < 0.001), 25(OH)DF (12.6 ± 4.2 vs. 16.7 ± 7.6 pg/mL, p < 0.001), 25(OH)DB [4.8 (2.3) vs. 6.1 (5.2) ng/mL, p = 0.012], and VDBP [112.2 (51.3) vs. 121.9 (95.5) µg/mL, p < 0.001] levels than the controls. The cutoff values for 25(OH)DT and 25(OH)DF levels for VDD were lower in the obese group than in the control group (9.4 vs. 14.1 ng/mL; 12.2 vs. 16.8 pg/mL, respectively).Conclusion: The vitamin D cutoff values for the diagnosis of VDD were different in the obese and control groups. Using the same cutoff value for VDD may cause overtreatment in obese adolescents. What is Known: • Vitamin D deficiency is more prevalent in obese children than nonobese controls, despite the same bone turnover markers and bone mineral density • The cutoff value of vitamin D level for the diagnosis of VDD is based on the PTH elevation What is New: • In obese adolescents, total and free vitamin D cutoff value for the diagnosis of VDD was lower than nonobese peers • Using the same cutoff value for vitamin D deficiency in both obese and nonobese adolescents may cause overtreatment.

Understanding the pathophysiological changes via untargeted metabolomics in COVID-19 patients.

Coronavirus disease 2019 (COVID-19) is an infectious respiratory disease caused by a new strain of the coronavirus. There is limited data on the pathogenesis and the cellular responses of COVID-19. In this study, we aimed to determine the variation of metabolites between healthy control and COVID-19 via the untargeted metabolomics method. Serum samples were obtained from 44 COVID-19 patients and 41 healthy controls. Untargeted metabolomics analyses were performed by the LC/Q-TOF/MS (liquid chromatography quadrupole time-of-flight mass spectrometry) method. Data acquisition, classification, and identification were achieved by the METLIN database and XCMS. Significant differences were determined between patients and healthy controls in terms of purine, glutamine, leukotriene D4 (LTD4), and glutathione metabolisms. Downregulations were determined in R-S lactoglutathione and glutamine. Upregulations were detected in hypoxanthine, inosine, and LTD4. Identified metabolites indicate roles for purine, glutamine, LTD4, and glutathione metabolisms in the pathogenesis of the COVID-19. The use of selective leukotriene D4 receptor antagonists, targeting purinergic signaling as a therapeutic approach and glutamine supplementation may decrease the severity and mortality of COVID-19.