The Effects of a Meldonium Pre-Treatment on the Course of the Faecal-Induced Sepsis in Rats

Sepsis is a life-threatening condition caused by the dysregulated and overwhelming response to infection, accompanied by an exaggerated pro-inflammatory state and lipid metabolism disturbance leading to sequential organ failure. Meldonium is an anti-ischemic and anti-inflammatory agent which negatively interferes with lipid metabolism by shifting energy production from fatty acid oxidation to glycolysis, as a less oxygen-demanding pathway. Thus, we investigated the effects of a four-week meldonium pre-treatment on faecal-induced sepsis in Sprague-Dawley male rats. Surprisingly, under septic conditions, meldonium increased animal mortality rate compared with the meldonium non-treated group. However, analysis of the tissue oxidative status did not provide support for the detrimental effects of meldonium, nor did the analysis of the tissue inflammatory status showing anti-inflammatory, anti-apoptotic, and anti-necrotic effects of meldonium. After performing tissue lipidomic analysis, we concluded that the potential cause of the meldonium harmful effect is to be found in the overall decreased lipid metabolism. The present study underlines the importance of uninterrupted energy production in sepsis, closely drawing attention to the possible harmful effects of lipid-mobilization impairment caused by certain therapeutics. This could lead to the much-needed revision of the existing guidelines in the clinical treatment of sepsis while paving the way for discovering new therapeutic approaches.     

Inhibitory Activities of Rare Ginsenoside Rg4 on Cecal Ligation and Puncture-Induced Sepsis

Sepsis is an uncontrolled response to inflammatory infection and is associated with high levels of mortality and morbidity. Rg4 is a rare ginsenoside mainly found in the leaves of Panax ginseng C. A. Meyer and the major protopanaxatriol-type ginsenoside of black ginseng. In this study, we determined whether Rg4 affects cecal ligation and puncture (CLP)-induced sepsis. Animals were separated into the following six groups: control group, CLP-operated group, CLP plus maslinic acid (MA), and CLP plus Rg4 (5, 10, or 15 mg/kg). Survival rate, body weight changes, inflammatory cytokines, and histological analyses were assessed. Human endothelial cells were activated with the high-mobility group box 1 (HMGB1) protein and Rg4. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used to assess inflammation and gene expression, respectively. After CLP surgery, the Rg4-administered group exhibited a higher survival rate and body weight compared with the untreated control group. Rg4 treatment reduced cytokine levels, including tumor necrosis factor (TNF)-α and interleukin (IL)-1β, as well as nitric oxide (NO) levels and renal inflammation. After Rg4 treatment of HMGB1-activated cells, the expressions of toll-like receptor (TLR) 4 and TNF-α were decreased, and the activation of phosphoinositide 3-kinase (PI3K)/AKT signaling increased cell viability. In summary, Rg4 inhibited inflammation and exhibited a protective effect against CLP-induced sepsis, thereby reinforcing cell survival against septic responses.     

Serial Change of Endotoxin Tolerance in a Polymicrobial Sepsis Model

Immune suppression is known to occur during sepsis. Endotoxin tolerance is considered a mechanism of immune suppression in sepsis. However, the timing and serial changes in endotoxin tolerance have not been fully investigated. In this study, we investigated serial changes in endotoxin tolerance in a polymicrobial sepsis model. Herein, we used a rat model of fecal slurry polymicrobial sepsis. After induction of sepsis, endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was measured at various time points (6 h, 12 h, 24 h, 48 h, 72 h, 5 days, and 7 days), through the measurement of TNF-α production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. At each time point, we checked for plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 levels. Moreover, we analyzed reactive oxygen species (ROS) as measured by 2′,7′-dichlorodihydrofluorescein, plasma lactate, serum alanine aminotransferase (ALT), and creatinine levels. Nuclear factor (NF)-κB, IL-1 receptor-associated kinase (IRAK)-M, and cleaved caspase 3 levels were measured in the spleen. Endotoxin tolerance, measured by TNF-α production stimulated through LPS in PBMCs and splenocytes, was induced early in the sepsis model, starting from 6 h after sepsis. It reached a nadir at 24 to 48 h after sepsis, and then started to recover. Endotoxin tolerance was more prominent in the severe sepsis model. Plasma cytokines peaked at time points ranging from 6 to 12 h after sepsis. ROS levels peaked at 12 h and then decreased. Lactate, ALT, and serum creatinine levels increased up to 24 to 48 h, and then decreased. Phosphorylated p65 and IRAK-M levels of spleen increased up to 12 to 24 h and then decreased. Apoptosis was prominent 48 h after sepsis, and then recovered. In the rat model of polymicrobial sepsis, endotoxin tolerance occurred earlier and started to recover from 24 to 48 h after sepsis.     

Exopolysaccharide Isolated from Lactobacillus plantarum L-14 Has Anti-Inflammatory Effects via the Toll-Like Receptor 4 Pathway in LPS-Induced RAW 264.7 Cells

Inflammation is a biological response of the immune system to defend the body from negative stimulation. However, the excessive inflammatory response can damage host tissues and pose serious threats. Exopolysaccharide (EPS), one of the postbiotics, is secreted from lactic acid bacteria. Although many studies have described the beneficial effects of EPS, such as its anti-inflammatory and anti-oxidant effects, its underlying mechanisms have remained to be poorly understood. Thus, we identified that EPS obtained from Lactobacillus plantarum L-14 was a homogeneous polysaccharide primarily comprised of glucose. To examine these anti-inflammatory effects, an inflammatory response was induced by lipopolysaccharide (LPS) administration to mouse macrophage RAW 264.7 cells that were pretreated with EPS. The anti-inflammatory effects of EPS were identified by analyzing the changes within inflammatory markers at the molecular level. We demonstrate here that EPS suppressed proinflammatory mediators, such as cyclooxygenase-2, interleukin-6, tumor necrosis factor-α, and interleukin-1β, and downregulated the expression of an inducible nitric oxide synthase known to lead to oxidative stress. It was also confirmed that EPS had anti-inflammatory effects by blocking the interaction of LPS with Toll-like receptor 4 (TLR4), as demonstrated by using the known TLR4 inhibitor TAK-242. In addition, we found that EPS itself could suppress the expression of TLR4. Consequently, our data suggest that EPS can be a potential target for the development of natural product-derived medicine for treating inflammatory diseases related to TLR4.     

中药对酒精性肝损伤的保护作用

长期大量饮酒导致的酒精性肝病是一类常见的危害人类健康的疾病,目前尚无确切的治疗方法。近年来,中草药在预防和治疗酒精性肝病方面的潜在疗效引起了人们的广泛关注。本文就近年来中草药在预防和治疗酒精性肝损伤方面的研究做一综述。     

Effects of Tyrosine and Tryptophan in Rats with Diet-Induced Obesity

Amino acids tyrosine (Tyr) and tryptophan (Trp) play a significant role in the regulation of energy metabolism, locomotor activity, and eating behavior. We studied the possibility of modulating these processes in obesity by increasing the pool of Tyr and Trp in the experimental diet. As a model of obesity, we used Wistar rats fed a diet with an excess specific energy value (HFCD) for 64 days. Trp led to a normalization of the rats’ body weight almost to the control level, but increased anxiety-like behavior and decreased long-term memory. The consumption of amino acids resulted in increased grip strength and impairment of short-term memory. The locomotor activity of animals decreased with age as a result of Tyr consumption, while Trp, on the contrary, prevented this. The Tyr supplementation led to the normalization of triglycerides and LDL. In the spleen cell lysates, amino acids suppressed the production of proinflammatory cytokines. The liver tissue morphology showed that the consumption of Tyr noticeably weakened the signs of fatty degeneration. The addition of Trp, on the contrary, led to an unfavorable effect, consisting of the appearance of a high number of large rounded fatty vacuoles. The data obtained indicate a more pronounced anti-inflammatory effect of Tyr as compared to Trp.     

The Dipeptidyl Peptidase-4 Inhibitor Linagliptin Ameliorates Endothelial Inflammation and Microvascular Thrombosis in a Sepsis Mouse Model

The pathophysiology of sepsis involves inflammation and hypercoagulability, which lead to microvascular thrombosis and compromised organ perfusion. Dipeptidyl peptidase (DPP)-4 inhibitors, e.g., linagliptin, are commonly used anti-diabetic drugs known to exert anti-inflammatory effects. However, whether these drugs confer an anti-thrombotic effect that preserves organ perfusion in sepsis remains to be investigated. In the present study, human umbilical vein endothelial cells (HUVECs) were treated with linagliptin to examine its anti-inflammatory and anti-thrombotic effects under tumor necrosis factor (TNF)-α treatment. To validate findings from in vitro experiments and provide in vivo evidence for the identified mechanism, a mouse model of lipopolysaccharide (LPS)-induced systemic inflammatory response syndrome was used, and pulmonary microcirculatory thrombosis was measured. In TNF-α-treated HUVECs and LPS-injected mice, linagliptin suppressed expressions of interleukin-1β (IL-1β) and intercellular adhesion molecule 1 (ICAM-1) via a nuclear factor-κB (NF-κB)–dependent pathway. Linagliptin attenuated tissue factor expression via the Akt/endothelial nitric oxide synthase pathway. In LPS-injected mice, linagliptin pretreatment significantly reduced thrombosis in the pulmonary microcirculation. These anti-inflammatory and anti-thrombotic effects were independent of blood glucose level. Together the present results suggest that linagliptin exerts protective effects against endothelial inflammation and microvascular thrombosis in a mouse model of sepsis.     

Quercetin Ameliorates Testicular Damage in Zucker Diabetic Fatty Rats through Its Antioxidant,Anti-Inflammatory and Anti-Apoptotic Properties

The aim of this study was to investigate the effects of quercetin (QUE) on the testicular architecture as well as markers of oxidative, inflammatory, and apoptotic profile of male gonads in Zucker diabetic fatty (ZDF) rats suffering from Type 2 diabetes mellitus in the absence or presence of obesity. QUE was administered orally at a dose of 20 mg/kg/day for 6 weeks. Morphometric analysis revealed that QUE treatment led to an improvement in testicular appearance, particularly in the case of Obese ZDF rats. Furthermore, a significant stabilization of the antioxidant capacity (p < 0.05), superoxide dismutase and catalase activity (p < 0.01), with a concomitant decrease in lipid peroxidation (p < 0.05) were observed in Obese ZDF animals exposed to QUE. Our data also indicate a significant decline in the levels of interleukin (IL)-1 (p < 0.05), IL-6 (p < 0.01) and tumor necrosis factor alpha (p < 0.001) following QUE supplementation to Obese ZDF rats in comparison with their respective control. Finally, a significant down-regulation of the pro-apoptotic BAX protein (p < 0.0001) was observed in Obese ZDF rats administered with QUE, while a significant Bcl-2 protein overexpression (p < 0.0001) was recorded in Lean ZDF animals when compared to their untreated control. As such, our results suggest that QUE is a potentially beneficial agent to reduce testicular damage in ZDF rats with Type 2 diabetes mellitus by decreasing oxidative stress, chronic inflammation, and excessive cell loss through apoptosis.     

Adaptation of Lipid Profiling in Depression Disease and Treatment: A Critical Review

Major depressive disorder (MDD), also called depression, is a serious disease that impairs the quality of life of patients and has a high incidence, affecting approximately 3.8% of the world population. Its diagnosis is very subjective and is not supported by measurable biomarkers mainly due to the lack of biochemical markers. Recently, disturbance of lipid profiling has been recognized in MDD, in animal models of MDD or in depressed patients, which may contribute to unravel the etiology of the disease and find putative new biomarkers, for a diagnosis or for monitoring the disease and therapeutics outcomes. In this review, we provide an overview of current knowledge of lipidomics analysis, both in animal models of MDD (at the brain and plasma level) and in humans (in plasma and serum). Furthermore, studies of lipidomics analyses after antidepressant treatment in rodents (in brain, plasma, and serum), in primates (in the brain) and in humans (in plasma) were reviewed and give evidence that antidepressants seem to counteract the modification seen in lipids in MDD, giving some evidence that certain altered lipid profiles could be useful MDD biomarkers for future precision medicine.     

Cardiac Lipid Metabolism Is Modulated by Casimiroa edulis and Crataegus pubescens Aqueous Extracts in High Fat and Fructose (HFF) Diet‐Fed Obese Rats

This study aim to evaluate the effect of Casimiroa edulis and Crataegus pubescens aqueous extracts on cardiac lipotoxicity in obese rats. Both extracts decrease cardiac hypertrophy and steatosis in high fat and fructose (HFF)‐diet‐fed obese rats. C. pubescens decreases the cardiac content of 16 and 18 carbon‐length fatty acids, whereas C. edulis extract does not alter the fatty acid profile. Regarding lipotoxic compounds, C. pubescens reduces the cardiac content of 16 and 18 carbon‐length ceramides and diacylglycerols, whereas C. edulis extract reduces ≥20 carbon‐length lipotoxic compounds. Both extracts down‐regulate fatty acid synthase (Fasn) and acetyl‐CoA carboxylase (Acaca) (lipogenesis), glyceril‐3‐phosphate acyltransferase (Gpat) (diacylglycerol synthesis) and serine palmitoyltransferase 1 (Spt1) (ceramide synthesis), and up‐regulate carnitine palmitoyltransferase 1 (Cpt1) and acyl‐CoA dehydrogenase (Acadm) (β‐oxidation), and the greatest effect is observed with C. pubescens. In addition, C. edulis exerts the greatest cardiac anti‐inflammatory activity, whereas C. pubescens shows the highest cardiac antioxidant activity. The cardioprotective effect of C. pubescens may be associated with its content of (?)‐epigallocatechin gallate, (+)‐catechin, chlorogenic acid, caffeic acid, and β‐campesterol, whereas the beneficial effect of C. edulis may be related to its high content of steroidal saponins and alkaloids. Therefore, these results demonstrate that both herbal aqueous extracts ameliorate cardiac lipotoxicity in HFF‐diet‐fed rats, and C. pubescens exerts a greater beneficial effect. Practical Applications: This study proposes the characterization of fatty acids and lipotoxic compounds (ceramides and diacylglycerols) of cardiac tissue in combination with the determination of the expression of specific genes related to lipid metabolism to identify the mechanisms associated with the cardioprotective effects of herbal extracts. The results obtained in this study demonstrate the cardioprotective potential of Casimiroa edulis and Crataegus pubescens aqueous extracts through the modulation of cardiac lipid metabolism in high fat and fructose diet fed obese rats. Therefore, these herbs can be used for the development of functional beverages or the extraction of bioactive compounds with cardioprotective effect.     

Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats

Metabolic syndrome is associated with an increased risk of colorectal cancer. This study investigated the impact of hypertension, a component of metabolic syndrome, on azoxymethane (AOM)-induced colorectal carcinogenesis using SHRSP/Izm (SHRSP) non-diabetic/hypertensive rats and SHRSP.Z-Lepr^fa/IzmDmcr (SHRSP-ZF) diabetic/hypertensive rats. Male 6-week-old SHRSP, SHRSP-ZF, and control non-diabetic/normotensive Wister Kyoto/Izm (WKY) rats were given 2 weekly intraperitoneal injections of AOM (20 mg/kg body weight). Two weeks after the last injection of AOM, the SHRSP and SHRSP-ZF rats became hypertensive compared to the control WKY rats. Serum levels of angiotensin-II, the active product of the renin-angiotensin system, were elevated in both SHRSP and SHRSP-ZF rats, but only the SHRSP-ZF rats developed insulin resistance, dyslipidemia, and hyperleptinemia and exhibited an increase in adipose tissue. The development of AOM-induced colonic preneoplastic lesions and aberrant crypts foci, was significantly accelerated in both SHRSP and SHRSP-ZF hypertensive rats, compared to WKY normotensive rats. Furthermore, induction of oxidative stress and exacerbation of inflammation were observed in the colonic mucosa and systemically in SHRSP and SHRSP-ZF rats. Our findings suggest that hypertension plays a role in the early stage of colorectal carcinogenesis by inducing oxidative stress and chronic inflammation, which might be associated with activation of the renin-angiotensin system.     

Ameliorative Effects of a Rhenium (V) Compound with Uracil-Derived Ligand Markers Associated with Hyperglycaemia-Induced Renal Dysfunction in Diet-Induced Prediabetic Rats

Kidney disease is characterised by the improper functioning of the kidney as a result of kidney damage caused by hyperglycaemia-induced oxidative stress. The moderate hyperglycaemia seen in prediabetes can be treated using a combination of metformin and lifestyle interventions (low-calorie diets and exercising). However, patients have been reported to over-rely on pharmacological interventions, thus decreasing the efficacy of metformin, which leads to the development of type 2 diabetes mellitus (T2DM). In this study, we investigated the effects of a rhenium (V) compound in ameliorating renal dysfunction in both the presence and absence of dietary modification. Kidney function parameters, such as fluid intake and urine output, glomerular filtration rate (GFR), kidney injury molecule (KIM 1), creatinine, urea, albumin and electrolytes, were measured after 12 weeks of treatment. After treatment with the rhenium (V) compound, kidney function was restored, as evidenced by increased GRF and reduced KIM 1, podocin and aldosterone. The rhenium (V) compound ameliorated kidney function by preventing hyperglycaemia-induced oxidative stress in the kidney in both the presence and absence of dietary modification.     

Hepatoprotective Effects of Albumin-Encapsulated Nanoparticles of a Curcumin Derivative COP-22 against Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Injury in Mice

Acute liver injury (ALI) is a severe syndrome and can further develop into acute liver failure (ALF) which can lead to high mortality and cause irreversible liver injuries in the clinic. Liver transplantation is the most common treatment; however, liver donors are lacking, and the progression of ALF is rapid. Nanoparticles can increase the bioavailability and the targeted accumulation of drugs in the liver, so as to significantly improve the therapeutic effect of ALI. Curcumin derivative COP-22 exhibits low cytotoxicity and effective anti-inflammatory activity; however, it has poor water solubility. In this study, COP-22-loaded bovine serum albumin (BSA) nanoparticles (22 NPs) were prepared and characterized. They exhibit effective hepatoprotective effects by inhibiting inflammation, oxidative stress, and apoptosis on Lipopolysaccharide/D-Galactosamine-induced acute liver injury of mice. The anti-inflammatory activity of 22 NPs is related to the regulation of the NF-κB signaling pathways; the antioxidant activity is related to the regulation of the Nrf2 signaling pathways; and the apoptosis activity is related to mitochondrial pathways, involving Bcl-2 family and Caspase-3 protein. These three cellular pathways are interrelated and affected each other. Moreover, 22 NPs could be passively targeted to accumulate in the liver through the retention effect and are more easily absorbed than 22.HCl salt in the liver.     

邻苯二甲酸单丁酯致小鼠肝脏和肾脏组织的氧化损伤

为了探究邻苯二甲酸单丁酯(MBP)对小鼠肝脏和肾脏的氧化损伤,将42只BALB/c小鼠随机分为7组,每组6只,分别为25mg·kg-1、50mg·kg-1、100mg·kg-1、200mg·kg-1的4个MBP染毒组、1个100mg·kg-1的邻苯二甲酸二丁酯(DBP)染毒组、1个空白对照组、1个溶剂对照组。染毒期间对小鼠的体征进行观察;14d后取其肝脏和肾脏组织,制作小鼠肝脏和肾脏组织的切片,对肝脏和肾脏的组织学形态进行观察;制作组织匀浆液用于检测肝脏和肾脏组织细胞的ROS、GSH、MDA的含量,以了解MBP对肝脏和肾脏组织的氧化损伤作用。结果显示:各剂量组小鼠肝细胞和肾小管上皮细胞均出现不同程度的细胞核固缩、细胞水肿、空泡样变、脂肪滴增大融合等症状;ROS和MDA的含量与MBP的染毒剂量呈正相关,GSH的含量与MBP的染毒剂量呈负相关;相同剂量的DBP与MBP染毒组相比,MBP染毒组的ROS和MDA含量较高、GSH含量较低。表明,MBP的暴露与小鼠肝脏和肾脏组织的氧化损伤存在直接联系。     

Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury

Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.     

The Effect of Low-Energy Laser-Driven Ultrashort Pulsed Electron Beam Irradiation on Erythropoiesis and Oxidative Stress in Rats

Anemia is a commonly observed consequence of whole-body exposure to a dose of X-ray or gamma irradiation of the order of the mean lethal dose in mammals, and it is an important factor for the determination of the survival of animals. The aim of this study was to unravel the effect of laser-driven ultrashort pulsed electron beam (UPEB) irradiation on the process of erythropoiesis and the redox state in the organism. Wistar rats were exposed to laser-driven UPEB irradiation, after which the level of oxidative stress and the activities of different antioxidant enzymes, as well as blood smears, bone marrow imprints and sections, erythroblastic islets, hemoglobin and hematocrit, hepatic iron, DNA, and erythropoietin levels, were assessed on the 1st, 3rd, 7th, 14th, and 28th days after irradiation. Despite the fact that laser-driven UPEB irradiation requires quite low doses and repetition rates to achieve the LD₅₀ in rats, our findings suggest that whole-body exposure with this new type of irradiation causes relatively mild anemia in rats, with subsequent fast recovery up to the 28th day. Moreover, this novel type of irradiation causes highly intense processes of oxidative stress, which, despite being relatively extinguished, did not reach the physiologically stable level even at the 28th day after irradiation due to the violations in the antioxidant system of the organism.     

The Effects of Silencing PTX3 on the Proteome of Human Endothelial Cells

The human long pentraxin PTX3 has complex regulatory roles at the crossroad of innate immunity, inflammation, and tissue repair. PTX3 can be produced by various cell types, including vascular endothelial cells (ECs), in response to pro-inflammatory cytokines or bacterial molecules. PTX3 has also been involved in the regulation of cardiovascular biology, even if ambiguous results have been so far provided in both preclinical and clinical research. In this study, we compared the proteomic profiles of human ECs (human umbilical vein ECs, HUVECs), focusing on differentially expressed proteins between the control and PTX3-silenced ECs. We identified 19 proteins that were more abundant in the proteome of control ECs and 23 proteins that were more expressed in PTX3-silenced cells. Among the latter, proteins with multifunctional roles in angiogenesis, oxidative stress, and inflammation were found, and were further validated by assessing their mRNAs with RT-qPCR. Nevertheless, the knock down of PTX3 did not affect in vitro angiogenesis. On the contrary, the lack of the protein induced an increase in pro-inflammatory markers and a shift to the more oxidative profile of PTX3-deficient ECs. Altogether, our results support the idea of a protective function for PTX3 in the control of endothelial homeostasis, and more generally, in cardiovascular biology.     

Effects of Lacosamide Treatment on Epileptogenesis,Neuronal Damage and Behavioral Comorbidities in a Rat Model of Temporal Lobe Epilepsy

Clinically, temporal lobe epilepsy (TLE) is the most prevalent type of partial epilepsy and often accompanied by various comorbidities. The present study aimed to evaluate the effects of chronic treatment with the antiepileptic drug (AED) lacosamide (LCM) on spontaneous motor seizures (SMS), behavioral comorbidities, oxidative stress, neuroinflammation, and neuronal damage in a model of TLE. Vehicle/LCM treatment (30 mg/kg, p.o.) was administered 3 h after the pilocarpine-induced status epilepticus (SE) and continued for up to 12 weeks in Wistar rats. Our study showed that LCM attenuated the number of SMS and corrected comorbid to epilepsy impaired motor activity, anxiety, memory, and alleviated depressive-like responses measured in the elevated plus maze, object recognition test, radial arm maze test, and sucrose preference test, respectively. This AED suppressed oxidative stress through increased superoxide dismutase activity and glutathione levels, and alleviated catalase activity and lipid peroxidation in the hippocampus. Lacosamide treatment after SE mitigated the increased levels of IL-1β and TNF-α in the hippocampus and exerted strong neuroprotection both in the dorsal and ventral hippocampus, basolateral amygdala, and partially in the piriform cortex. Our results suggest that the antioxidant, anti-inflammatory, and neuroprotective activity of LCM is an important prerequisite for its anticonvulsant and beneficial effects on SE-induced behavioral comorbidities.     

Opioids and Sepsis: Elucidating the Role of the Microbiome and microRNA-146

Sepsis has recently been defined as life-threatening organ dysfunction caused by the dysregulated host response to an ongoing or suspected infection. To date, sepsis continues to be a leading cause of morbidity and mortality amongst hospitalized patients. Many risk factors contribute to development of sepsis, including pain-relieving drugs like opioids, which are frequently prescribed post-operatively. In light of the opioid crisis, understanding the interactions between opioid use and the development of sepsis has become extremely relevant, as opioid use is associated with increased risk of infection. Given that the intestinal tract is a major site of origin of sepsis-causing microbes, there has been an increasing focus on how alterations in the gut microbiome may predispose towards sepsis and mediate immune dysregulation. MicroRNAs, in particular, have emerged as key modulators of the inflammatory response during sepsis by tempering the immune response, thereby mediating the interaction between host and microbiome. In this review, we elucidate contributing roles of microRNA 146 in modulating sepsis pathogenesis and end with a discussion of therapeutic targeting of the gut microbiome in controlling immune dysregulation in sepsis.     

The hypoglycemic effect of the kelp on diabetes mellitus model induced by alloxan in rats

Hypoglycemic effects and the use of kelp in diabetes mellitus (DM) model rats induced by alloxan were investigated. Sixty healthy male rats were used to establish DM models by injecting alloxan intraperitoneally. Kelp powder was added to the general forage for the rats. The levels of fasting blood glucose (FBG) were determined by an automatic blood glucose device. Electrochemiluminescence immunoassay was applied to determine the serum levels of insulin. The serum levels of malondialdehyde (MDA) were measured by thiobarbituric acid assay and nitric oxide (NO) by nitrate reductase assay. The activities of superoxide dismutase (SOD) were determined by xanthinoxidase assay and glutathione peroxidase (GSH-Px) by chemical colorimetry. The shape and structure of islet cells were observed with Hematine-Eosin staining, and the expression of superoxide dismutase (SOD) and inducible nitric oxide synthase (iNOS) in islet cells were detected by immunohistochemical assay. The results showed that the serum levels of insulin after treatment with kelp powder increased significantly compared to those in the DM-model group, while the FBG in the medium-high dose treated groups decreased significantly compared to those in the DM-model group (P < 0.05). The levels of MDA and NO in the kelp powder groups were lower than those in the DM-model group, while the activities of SOD and GSH-Px were higher than those in the DM-model group, of which a significant difference existed between the medium-high dose treated groups and the DM-model group (P < 0.05). The shape and structure of islet cells improved with the up-expressing SOD and down-expressing iNOS in the medium-high dose treated groups compared to those in the DM-model group (P < 0.05). There were no significant differences between the medium and high dose treated groups, all above indexes (P > 0.05). It is suggested that kelp might aid recovery of the the islet cell secreting function and reduce the level of FBG by an antioxidant effect.