Decreased Blood Levels Research Articles

Effects of saffron (Crocus sativus L. Iridaceae) on blood levels of sex hormones, sexual behavior and number of offspring in rats

This paper presents the results of the study of the effects of Azerbaijan-grown saffron (Сrocus sativus L. Iridaceae) on the blood level of follicle-stimulating hormone (FSH) and a number of offspring in female rats, as well as on the blood level of testosterone and sexual behavior in male rats. The findings revealed a decrease in blood levels of FSH in 12-month-old female rats as compared to the control group (comprising animals of the same age that did not receive the saffron extract), as they approximated the registered levels of 6-month-old female rats. Saffron increased the blood level of testosterone as compared to untreated controls, which did not receive saffron. Per os administration of saffron also resulted in a notable increase in the number of pups from female rats which had received the saffron extract prior to pairing with the intact males, as well as manifested stimulation of proceptive and receptive components of sexual behavior in male rats.

Does Vitamin D matter? The role of calcium homeostasis imbalance in clinical severity of psychiatric patients

IntroductionVitamin D modulates the biosynthesis of neurotransmitters and neurotrophic factors and it is involved in the modulation of inflammatory responses, with a potential impact on clinical status of patients with severe mental disorders. Moreover, available evidences report that decreased blood levels of Vitamin D are associated to a worse course of psychotic and affective disorders.ObjectivesWe assessed calcium homeostasis imbalance in a sample of inpatients and outpatients, referring to the Department of Psychiatry of University of Campania “Luigi Vanvitelli” in order to explore levels of Calcium, PTH and Vitamin D and their influence in clinical severity among this different subgroups.MethodsAll patients were administered The Brief Psychiatric Rating Scale (BPRS) to assess different domains of psychopathology. Vitamin D, Calcium and PTH levels were assessed in all patients. An-ad hoc schedule was administered for socio-demographic and clinical characteristics.ResultsThe total sample consisted of 152 patients (75 males and 77 females with 47.3 ± 14.4 age at admission, 74 inpatients and 78 outpatients). Patients with lower level of Vitamin D are more likely to present higher number of relapses (p<0.05) and to be inpatients (<0.01). Finally, serum levels of Vitamin D were negatively correlated with all the BPRS subscales (p < 0.01).ConclusionsLower levels of Vitamin D correlate with a worse clinical outcome of patients with different psychiatric diagnosis. Our results highlight the importance to routinely assess PTH, Vit D and calcium levels, especially in inpatients. Moreover, Vitamin D may represent a valid add-on treatment for these patients.DisclosureNo significant relationships.

The influence of bariatric (metabolic) surgery on blood polyunsaturated fatty acids: A systematic review.

Bariatric, also termed metabolic, surgery is an increasingly common treatment for severe and complex obesity. It decreases macronutrient intake, influences nutrient absorption and modifies gastrointestinal physiology with the aim of reducing adiposity, improving metabolism and reducing disease risk. Bariatric surgery has been shown to result in micronutrient deficiencies. Whether it results in deficiencies of essential fatty acids (EFAs) and their bioactive polyunsaturated fatty acid (PUFA) derivatives is not clear. The aim of this systematic review is to identify whether there are effects of bariatric surgery on the blood levels of EFAs and other PUFAs. A database search was conducted up to November 2020 using Medline, Embase and Cinahl databases, using relevant search terms identified by a PICO protocol. Only human studies reporting on PUFAs in a blood pool, published in the English language and available in full text were included. The Cochrane tool for assessing risk of bias was used and data were extracted. Fifteen papers from fourteen studies with relevant data were identified for inclusion. Studies differed according to surgical intervention, duration, measured timepoints, sample size and PUFAs reported. Both increases and decreases in selected PUFAs were reported in different studies. For the EFAs linoleic acid and α-linolenic acid and for the longer-chain omega-3 PUFA eicosapentaenoic acid, bariatric surgery is associated with a transient decline in status (to about 6 months post-surgery) with a later return to pre-surgery levels. All studies had some risk of bias and most studies were of small size. There is a decrease in blood levels of both EFAs and of eicosapentaenoic acid in the months following bariatric surgery. This may partly counter the desired effects of the surgery on blood lipids, insulin sensitivity and inflammation. Nutritional strategies (e.g. use of modified formulas or of supplements) may be able to correct the decrease in those PUFAs. Nevertheless, the observed decrease in PUFAs is transient.

The Effect of Saffron (<i>Crocus sativus L. Iridaceae</i>) Orally Administration on Blood Level of Sex Hormones in Rats

Modern medicine is currently marked by an increased interest in herbal pharmaceutical drugs traditionally applied in folk medicine in a significant number of diseases. In this regard, saffron (<i>Crocus sativus L. Iridaceae</i>) is of particular importance. This paper presents the results of study of the effects of Azerbaijan-grown saffron on blood level of follicle-stimulating hormone (FSH) in female rats, as well as on blood level of testosterone in male rats. In the blood serums of animals, using hormonal test systems for enzyme immunoassay, FSH and testosterone levels were determined. The findings revealed a decrease in blood levels of FSH in 12-month-old female rats as compared to the control group (comprising animals of the same age which did not receive the saffron extract), as they approximated the registered levels of 6-month-old female rats. Saffron increased the blood level of testosterone as compared to untreated controls, which did not receive saffron. Saffron’s unique medicinal properties largely owe to the diversity of biologically active substances it contains The effects of saffron treatment observed in the course of this study could be explained by the direct impact of saffron and its components on the sex glands and the central nervous system. Findings of diverse pharmacological effects of the saffron extract open new horizons for the development of scientifically corroborated recommendations for application in practical medicine.

Роль нейротрофического фактора мозга (BDNF) в физической активности (обзор)

The review focuses on one of the brain-derived neurotrophic factors (BDNF) and its role in human physical activity. BDNF is a protein found in many areas of the brain including, e.g., the hippocampal cortex. The paper provides evidence that BDNF is instrumental in the development (e. g., in cell differentiation, cell migration to a specific location, growth of dendrites, synaptogenesis), survival and maintenance of neuron activity. The paper describes the mechanisms of BDNF synthesis. It is shown that this neurotrophic factor is present in microglial cells, lymphocytes, monocytes, and skeletal muscle cells. It can also cross the blood-brain barrier. It is a critical component in the origin of long-term potentiation-related changes in synapses. BDNF helps maintain high levels of concentration and attention and may play a role in protecting the brain from damage. Decreased blood levels of BDNF in newborns may increase the risk of developing ASD, ADHD, post-traumatic stress disorder, and bipolar disorder. Learning and memory processes are associated with structural changes in dendritic spines in the hippocampus, cortex, and amygdala, and BDNF modulates the number and structure of dendritic spines both during the development and in the adult brain. Physical activity increases the level of BDNF in several ways. One of these mechanisms is associated with lactate, which appears as a result of human physical activity, and is also the most important signaling molecule. The higher the lactate level, the higher the BDNF level. The improvement in cognitive function after physical activity has also been attributed to high serum levels of BDNF.

N-3 PUFA ameliorated bone loss induced by postmenopausal depression following exposure to chronic mild stress and maternal separation by regulating neuronal processes

Depression induced by chronic mild stress (CMS) reduced bone mass in ovariectomized (OVX) rats, and maternal separation (MS) during early life aggravated depression-induced bone mass destruction. N-3 polyunsaturated fatty acids (PUFA) have been shown to improve bone mass and depression, but the bone-protecting effects of n-3 PUFA were unclear in CMS+MS-induced depression models. The purpose of this study was to determine whether n-3 PUFA improved CMS+MS-induced postmenopausal bone loss via its antidepressant-like action. Rats were fed diets containing 0% of total energy intake (en %) of n-3 PUFA during lifetime or 1 en % n-3 PUFA during pre-weaning or post-weaning periods, or their entire lifetimes and were allocated to CMS or CMS+MS groups after OVX. Lifetime supply of n-3 PUFA enhanced bone mass and microarchitecture, and expression of runt-related transcription factor 2, while decreasing blood levels of amino-terminal cross-linked telopeptide of type 1 collagen and the expression of receptor activator of nuclear factor kappa Β ligand/osteoprotegerin, activating transcription factor 4, and adrenergic receptor β2. Lifetime supply of n-3 PUFA decreased levels of adrenocorticotropic hormone and corticosterone and the expression of corticotropin-releasing factor in the brain but increased expression of the glucocorticoid receptor, serotonin-2C receptor, cAMP response element-binding protein (CREB), and calmodulin kinase IV and serotonin levels. Supply of n-3 PUFA during the pre-and post-weaning periods had beneficial effects on the brain but not on the bones. Lifetime supply of n-3 PUFA ameliorated bone loss induced by chronic stress by regulating hypothalamic-pituitary-adrenal axis activity and serotonin-CREB signaling.

Moringa Leaf Powder (Moringa oleifera) Decrease of Inflammation Plasma Cytokine of Pregnant Rats with Diabetes Mellitus

BACKGROUND: Preeclampsia is a major obstetric problem worldwide, especially in developing countries that can cause maternal and fetal morbidity and mortality that affect 2–10% of pregnancies worldwide. More than 4 million pregnant women each year develop preeclampsia and cause 15–20% of maternal deaths worldwide. There are several high-risk factors associated with preeclampsia. Diabetes mellitus is one of the risk factors for preeclampsia. Preeclampsia has been shown to have higher levels of Th1 (pro-inflammatory) products and lower levels of Th2 (anti-inflammatory) products compared to normal pregnancy in blood serum. Interleukin (IL) 1, IL-2, IL-8, tumor necrosis factor (TNF)-alpha, and interferon gamma are Th1 cytokines or pro-inflammatory cytokines that can induce inflammatory reactions and are associated with pregnancy complications such as repeated abortion, preterm labor, rupture of membranes. preeclampsia, and stunted fetal growth. In contrast, Th2 cytokines such as transforming growth factor-β (TGF-β), IL-4, IL-5, IL6, and IL-10 are associated with normal pregnancy. AIM: This study aims to prove the effect of giving Moringa leaf powder (M. oleifera) to decrease blood levels, , so this study will answer the effect of Moringa oleifera leaf powder on blood level of IL-6, IL-10, TNF-α and TGF-β METHODS: A total of 30 rats were checked for sugar levels on day 4 after being induced by alloxan for 18 days to see if the rats were already in a hyperglycemic state. Then, they were divided into six groups, each group contained five pregnant white rats. Group 1 was the negative group (without being given alloxan), Group 2 was positive (given alloxan 150 mg/day/kg BW), and Groups 3, 4, 5, and 6 were given alloxan 150 mg/day/kg BW and each given a dose of 100 Moringa leaf powder; 200, 400, and 800 mg/day/kg body weight. After alloxan was induced and given a dose of Moringa leaf powder according to each group, blood samples were taken to separate the serum and continued with the ELISA method to calculate the levels of IL-6, IL-10, TNF-α, and TGF-β. RESULTS: The administration of Moringa leaf powder at a dose of 800 mg/day/kg BW was able to increase the levels of IL-10 in the positive control Group 4 by 7.211 mIU/ml and reduced levels of IL-6 in the 8th dose group by giving Moringa leaf powder as much as 800 mg/day/kg body weight by 2.112 mIU/ml, was able to increase TGF-β levels in the dose Group 4 by giving Moringa leaf powder as much as 800 mg/day/kg BW, amounted to 1049.066 mIU/ml, and decreased TNF-α levels in the dose Group 4 by giving Moringa leaf powder as much as 800 mg/day/kg BW mIU/ml. CONCLUSION:The administration of Moringa leaf powder was able to increase the levels of IL-10 in the positive control Group, reduced levels of IL-6, was able to increase TGF-β levels, and decreased TNF-α levels.

Assessment of the Nephroprotective Properties of the Erythropoietin Mimetic Peptide and Infliximab in Kidney Ischemia-Reperfusion Injury in Rats.

Chronic kidney disease (CKD) or acute kidney injury (AKI) causes impaired kidney function, leading to cognitive impairment, neuropathy, and cerebrovascular disease. Due to kidney damage, toxinsstay in thebloodrather thanleavingthebodythrough the urine, and brain function is affected by kidney-brain interaction. The present study aimed to investigate the protective effects of erythropoietin mimetic peptide (pHBSP) and infliximab on ischemic renal reperfusion injury. The experiment was performed on 70 white male Wistar laboratory rats which received recombinant erythropoietin, pHBSP, and infliximab. Under anesthesia, traumatic vascular clamps were applied to the left renal pedicle for 40 min, and nephrectomy was performed on the right. Functional tests and laboratory tests were performed 5 min and 24 h after the reperfusion. Thereafter, 24 h after the surgery, the plasma creatinine and urea levels in the sham-operated animals were obtained at 45.9±0.8 mmol/L and 6.7±0.2 mmol/L, respectively. Plasma creatinine and urea levels in the control group animals were 102.63±3.6 mmol/L and 21.80±1.29 mmol/L, respectively. The administration of pHBSP and infliximab to the animals with ischemia-reperfusion kidney injury has a pronounced nephroprotective effect, as compared to erythropoietin. There was a significant decrease in blood levels of creatinine and urea, improvement of microcirculation in the kidney, normalization of glomerular filtration rate, and fractional sodium excretion. The results of the study demonstrated pointed to the prospects of pHBSP and infliximab administration in ischemia-reperfusion kidney injury and justified the feasibility of further research in this field.

Betaine supplementation to rats alleviates disturbances induced by high-fat diet: pleiotropic effects in model of type 2 diabetes.

Betaine is a biologically active compound exerting beneficial effects in the organism, however, the exact mechanisms underlying its action are not fully elucidated. The present study aimed to explore, whether betaine alleviates disorders induced by feeding rats a high-fat diet (HFD). Rats were divided into 3 groups: control, fed an HFD and fed an HFD and receiving betaine (2% water solution for 8 weeks). Betaine improved glucose tolerance, decreased blood levels of non-esterified fatty acids and prevented lipid accumulation in the skeletal muscle of rats on an HFD. Betaine reduced activities of blood alanine aminotransferase, blood levels of bilirubin and hepatic lipid content. Expression of fatty acid synthase in the liver and the skeletal muscle was decreased in response to feeding an HFD, and this effect was deepened by betaine in the muscle tissue. Hepatic and muscular expression of genes related to insulin signaling were unchanged in HFD-fed rats. Lipolysis stimulated by epinephrine (an adrenergic receptor agonist), forskolin (an activator of adenylate cyclase), dibutyryl-cAMP (an activator of protein kinase A) and DPCPX (an adenosine A1 receptor antagonist) was diminished in the adipocytes of rats fed an HFD, however, this effect was alleviated by betaine. Moreover, blood leptin levels in HFD-fed rats were elevated, whereas leptinemia have normalized by betaine supplementation. Betaine prevented the increase in expression of N-methyl D-aspartate receptors in the hippocampus and in the cerebral cortex. These results indicate that betaine positively affects the insulin-sensitive tissues: liver (hepatoprotective effects), skeletal muscle (reduced lipid accumulation) and adipose tissue (a rise in lipolysis), which is associated with improved insulin sensitivity. Betaine-induced prevention of hyperleptinemia indicates restoration of leptin action, and changes in the brain reveal neuroprotective properties. Our results show that betaine induces positive changes in HFD-fed rats, its action is pleiotropic and involves different tissues.

Clinical characteristics and genetic analysis of neonatal intrahepatic cholestasis caused by citrin deficiency in comparison with idiopathic neonatal cholestasis.

To compare the clinical and genetic characteristics of patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and idiopathic neonatal cholestasis (INC). The clinical data of 30 patients with NICCD and 30 patients with INC admitted in Children's Hospital of Chongqing Medical University during September 2012 and December 2017 were retrospectively analyzed. The clinical manifestations, biochemical indicators and genetic characteristics were compared between two groups. Patients in both groups presented similar clinical manifestations, however the chubby face and clay-colored stool were more common in NICCD patients (both <0.01). Comparing with INC group, NICCD group showed significantly decreased blood levels of glucose, prealbumin, albumin, total protein, fibrinogen, and aminotransferases (<0.05 or <0.01), while significantly increased blood levels of indirect bilirubin, total bile acid, alkaline phosphatase, lactic dehydrogenase, ammonium, alpha fetoprotein, and markers of coagulation function (<0.05 or <0.01). In addition, NICCD patients showed remarkably increased blood levels of citrulline, methionine, tyrosine, arginine, and threonine; as well as significantly increased urine levels of 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvic acid and phenyllactic acid, while those indicators in INC patients were normal (all <0.01). All the patients with NICCD had mutation including 8 homozygotes, 9 compound heterozygotes, and 13 single heterozygotes. Among all mutations, c.851_854del was most common (53.19%), c.1196T>A and c.919G>T were two novel mutations. The manifestations of chubby face and clay-colored stool may provide clue for early diagnosis of NICCD along with the elevated biochemical parameters, such as ammonium, alpha-fetal protein, citrulline in blood and 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvic acid, phenyllactic acid in urine. Target gene trapping and high-throughput sequencing have the key values in diagnosis and differential diagnosis of NICCD.

The role of zinc in the prevention and treatment of nonalcoholic fatty liver disease

The zinc element is an essential nutrient for human health. Zinc is involved in the glucose, lipid, and protein metabolism and antioxidant processes in biological pathways. Zinc deficiency can lead to several chronic liver diseases. Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases where zinc deficiency plays a critical role in pathogenesis. Human and animal studies showed that both NAFLD risk factors (i.e., insulin resistance, diabetes mellitus, dyslipidemia, obesity, hypertension) and NAFLD itself are associated with decreased blood levels of zinc. Additionally, endoplasmic reticulum stress and inflammation due to unfolded protein response, inadequate dietary zinc intake, and decreased zinc absorption from the gastrointestinal tract can result in zinc deficiency leading to NAFLD. Herein, we reviewed the mechanistic links between zinc deficiency and NAFLD development and the role of zinc in the prevention and treatment of NAFLD.

Comparison of Bone Mineral Density and Markers of Bone Turnover in Osteoporotic Women after 6-Month Treatment with Alendronate or Bazedoxifene: A Randomized Controlled Trial.

BackgroundIn a randomized controlled trial, we compared the bone mineral densities (BMDs) and blood markers of bone turnover during short-term treatment of osteoporotic women with bisphosphonate alendronate or bazedoxifene, a selective estrogen receptor modulator.MethodsTen and eleven patients were randomized to the alendronate and bazedoxifene groups, respectively. BMDs were measured before and after 6 months of treatment. Blood tests were used to measure the levels of osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX), vitamin D3, and parathyroid hormone pretreatment and after 3 and 6 months of treatment. The variables were compared statistically.ResultsThe alendronate group showed decreases in blood levels of both OC and CTX during the study period (P<0.001 and P=0.002, respectively), while the bazedoxifene group had a decrease only in OC levels (P=0.012). After 6 months of treatment, BMDs significantly increased in the alendronate group at multiple bone sites, including the L1–4 lumbar vertebrae, femur trochanter, and total femur. However, there was no significant increase in BMD in the bazedoxifene group. BMDs were not significantly different between the 2 groups.ConclusionsPatients treated with alendronate showed more rapid suppression of markers of bone turnover and higher BMD than those treated with bazedoxifene during a short-term regime. Considering the effects and complications of each medication, the relationship between bone turnover rate and bone quality will need to be investigated in future studies.

Impact of CytoSorb on kinetics of vancomycin and bivalirudin in critically ill patients.

CytoSorb is a promising tool to treat severe inflammatory status with multiple mechanisms in the acute care setting. Its effect on drugs is, however, poorly documented in vivo, although removal of small molecules might translate into decreased blood levels of life-saving medications. The aim of this study was to assess the impact of CytoSorb on vancomycin and bivalirudin clearance in a large population of critically ill patients. We performed a single-center analysis of CytoSorb treatments performed between January 2018 and March 2019 in critically ill patients admitted to our intensive care unit. A total of 109 CytoSorb treatments were performed in 89 patients. A decrease in lactate dehydrogenase (P=.007), troponin T (P=.022), and creatine phosphokinase (P=.013) was reported during treatment. Vancomycin dose required significant adjustments during treatment (P<.001), but no significant change was necessary after the first 3days. Similarly, the requirements of bivalirudin significantly changed over days (P<.001), but no dose adjustment was needed after the first 3days of treatment. No differences in terms of vancomycin and bivalirudin dose need was observed between patients on extracorporeal membrane oxygenation and those who were not (P=.6 and P=.6, respectively), between patients with and without continuous veno-venous hemofiltration (P=.9 and P=.9, respectively), and between CytoSorb responders or not (P=.4 and P=.7, respectively). CytoSorb is effective in mitigating the systemic inflammatory response and safe with respect to vancomycin and bivalirudin administration. These preliminary data further support the use of CytoSorb as adjunct therapy in critically ill patients.

Effect of vortioxetine on proinflammatory cytokine levels in patients with heart failure and comorbid depression

IntroductionSeveral studies have shown impaired cytokine status in both patients with depression and chronic heart failure (HF).Objectivesto study the effect of vortioxetine on the level of pro-inflammatory cytokines: interleukin -1β (IL-1β) and interleukin - 6 (IL-6).Methodsthere were examined 80 patients with HF with reduced ejection fraction (HFrEF) of ischemic genesis with functional class (FC) II-III (NYHA), 37 patients were without depression, 43 - with mild or moderate depressive disorders. Those with mild or moderate depressive disorders were divided into 2 subgroups: 21 patients received psychotherapy, 22 patients, in addition to psychotherapy, were prescribed vortioxetine at a dose of 10 mg / day in the morning after meals. The control group consisted of 20 healthy individuals. The level of cytokines in the blood was determined by ELISA method.ResultsPatients with CHF have an increase in levels of pro-inflammatory cytokines. Thus, the concentration in the serum of IL-1β was 2.3 times higher than the same indicator in the control group: (56.45 ± 4.17) pg / ml, against (24.71 ± 4.21) pg / ml p &lt;0.001). Depression caused an additional increase in the levels of IL-1β by 13.5% (p &lt;0.05) and IL-6 - by 17.3% (p &lt;0.01). Additional administration of vortioxetine caused a more rapid decrease in blood levels of both IL-1β (HR 0.87 [95% CI 0.72-0.97; p = 0.034]) and IL-6 (HR 0.81 [95% CI 0.68-0.93; p = 0.029]).ConclusionsThus, vortioxetine causes a decrease in the concentration of pro-inflammatory cytokines IL-1β and IL-6 in patients with HF and comorbid depression.DisclosureNo significant relationships.

The role of Vit D and parathyroid hormone in clinical severity of patients with bipolar disorder

IntroductionVitamin D modulates the biosynthesis of neurotransmitters and neurotrophic factors, thus influencing mood and its alterations. Decreased blood levels of Vitamin D are involved in many psychiatric disorders, in particular, affective disorders. As regards bipolar disorder (BD), an association between vitamin D deficiency and severity of illness has been found.ObjectivesIn this observational study, we assessed calcium homeostasis imbalance in a sample of patients with BD; in particular, we explored whether serum levels of PTH, Vitamin D and calcium influence the clinical presentation of BD and its symptom severity.MethodsAll patients were administered with validated assessment instruments to assess psychopathology, affective temperaments and global functioning. Vitamin D and PTH levels were assessed in all patients. An-ad hoc schedule was administered for socio-demographic and clinical characteristics.ResultsThe total sample consisted of 199 patients (females: 51%; mean age: 47.1 ± 13.2 years). Levels of serum PTH were directly correlated with the total number of hospitalizations (p&lt; 0.01), and of depressive (p&lt; 0.0001), manic (p&lt; 0.001) and hypomanic episodes (p&lt; 0.01). Serum levels of Vitamin D were positively associated with age at first psychiatric contact and were inversely correlated with the total number of depressive episodes (p&lt; 0.05) and cyclothymic temperament (p&lt; 0.05).ConclusionsIncreased levels of PTH and Vit D correlate with a worse clinical outcome of patients with BD. Our results highlight the importance to routinely assess PTH, Vit D and calcium levels in BD patients. Moreover, vitamin D may represent a valid add-on treatment for these patients.DisclosureNo significant relationships.

Herbal medicine WangShiBaoChiWan improves gastrointestinal health in mice via modulation of intestinal tight junctions and gut microbiota and inhibition of inflammation

WangShiBoChiWan (WSBCW) is a commonly used Chinese herbal medicine for the treatment of functional gastrointestinal disorders. However, its preclinical efficacy and the mechanisms of action have not been adequately studied. The goals of this study were to evaluate the effects of WSBCW on gastrointestinal health and modulation of related biomarkers. Female C57BL mice were randomly assigned into one of the experimental groups consisting of the control, drug controls, and WSBCW at 40, 120, and 360 mg/kg BW. Whole gut transit, small intestinal motility, and intestinal barrier permeability were determined. The castor oil-induced diarrhea mouse model was used to determine the effect of WSBCW on the diarrhea type of irritable bowel syndrome (IBS-D). WSBCW increased whole gut transit and intestinal motility, improved intestinal permeability in healthy animals and alleviated diarrhea symptoms in IBS-D mice. WSBCW upregulated intestinal junction proteins, increased the abundance of Bifidobacterium genus, Desulfovibrio genus and inhibited Bacteroides fragillis group in the gut microbiota, increased intestinal villi lengths, and decreased blood levels of inflammatory cytokines. Our study provided preclinical evidence to verify the effectiveness of WSBCW in gastrointestinal health and elucidate mechanistic insights. The results warrant further investigations to evaluate the therapeutic efficacy of WSBCW on gastrointestinal disorders, such as IBS and IBD.

The altered expression of neurofilament in mouse models and patients with spinal muscular atrophy.

ObjectivesTo investigate the levels of neurofilaments (NFs) in transgenic mice and patients with spinal muscular atrophy (SMA), and to evaluate their efficacy as a biomarker in SMA.MethodsThe levels of NF mRNA transcripts were measured by quantitative real‐time PCR in spinal cord from SMA mice. Blood levels of NF heavy chain (NfH) from mice and patients were measured by an in‐house ELISA method. The response of NFs to therapeutic intervention was analysed in severe SMA mice treated with morpholino antisense oligonucleotides.ResultsSignificant changes in NF transcript and protein in spinal cord and protein levels in blood were detected in SMA mice with severe or mild phenotypes, at different time points. A decrease in blood levels of NfH after antisense oligonucleotide treatment was only transient in the mice, despite the persistent benefit on the disease phenotype. A drastic reduction of over 90% in blood levels of NfF was observed in both control and SMA mice during early postnatal development. In contrast, blood levels of NfH were found to be decreased in older SMA children with chronic disease progression.InterpretationOur results show that blood NfH levels are informative in indicating disease onset and response to antisense oligonucleotides treatment in SMA mice, and indicate their potential as a peripheral marker reflecting the pathological status in central nervous system. In older patients with chronic SMA, however, the lower NfH levels may limit their application as biomarker, highlighting the need to continue to pursue additional biomarkers for this group of patients.

Association of neonatal blood levels of brain-derived neurotrophic factor with development of autism spectrum disorder: a systematic review and meta-analysis.

Our goal was to evaluate the association between neonatal blood brain-derived neurotrophic factor (BDNF) level and autism spectrum disorder (ASD) diagnosis later in life. MEDLINE and Web of Science databases were searched from inception until September 16, 2020. Reference lists of all relevant articles also were reviewed. Mean blood BDNF concentrations, standard deviations, sample sizes, and other data needed for calculation of effect sizes were extracted by two independent investigators. The quality of the included studies was appraised using the Newcastle-Ottawa Scale for case-control studies. Data were pooled using the random-effects model. Five case-control studies involving 1341 cases and 3395 controls were included in the meta-analysis. The meta-analysis of all included studies showed no significant difference in blood BDNF levels between neonates diagnosed with ASD later in life and healthy controls [standardized mean difference (SMD) = 0.261; 95% confidence interval (CI) - 0.052 to 0.573; P = 0.102], with high level of heterogeneity (Q = 64.346; I2 = 93.784; P < 0.001). A subgroup analysis by assay type showed decreased blood BDNF levels in ASDs compared to controls (SMD = - 0.070; 95% CI - 0.114 to - 0.026; P = 0.002), with high level of homogeneity (Q = 0.894; I2 = 0.000; P = 0.827). No evidence of publication bias was observed. Neonates diagnosed with ASD later in life have decreased blood levels of BDNF measured by double-antibody immunoassay. More studies are warranted to facilitate a more robust conclusion.

N-3 PUFA improved post-menopausal depression induced by maternal separation and chronic mild stress through serotonergic pathway in rats—effect associated with lipid mediators

Early life maternal separation (MS) increases the vulnerability to depression in rats with chronic mild stress (CMS). N-3 polyunsaturated fatty acids (PUFA) improved depressive behaviors in rats with acute stress; however, their effects on rats with MS+CMS were not apparent. The purpose of the present study was to investigate the hypothesis that lifetime n-3 PUFA supplementation improves post-menopausal depression through the serotonergic and glutamatergic pathways while modulating n-3 PUFA-derived metabolites. Female rats were fed diets of either 0% n-3 PUFA during lifetime or 1% energy n-3 PUFA during pre-weaning, post-weaning, or lifetime periods. Rats were allocated to non-MS or MS groups and underwent CMS after ovariectomy. N-3 PUFA increased brain n-3 PUFA-derived endocannabinoid/oxylipin levels, and reversed depressive behaviors. N-3 PUFA decreased blood levels of adrenocorticotropic hormone and corticosterone, and brain expressions of corticotropin-releasing factor and miRNA-218, which increased the expression of the glucocorticoid receptor. N-3 PUFA decreased the expression of tumor necrosis factor-α, interleukin (IL)-6, IL-1β, and prostaglandin E2, while increased the expression of miRNA-155. N-3 PUFA also increased brainstem serotonin levels and hippocampal expression of the serotonin-1A receptor, cAMP response element-binding protein (CREB), phospho-CREB, and brain-derived neurotrophic factor. However, n-3 PUFA did not affect brain expression of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subtype 1, N-methyl-D-aspartate receptor subtype 2B, or miRNA-132. Moreover, n-3 PUFA exposure during lifetime caused greater effects than pre- and post-weaning periods. The present study suggested that n-3 PUFA improved depressive behaviors through serotonergic pathway while modulating the metabolites of n-3 PUFA in post-menopausal depressed rats with chronic stress.

АКТИВАЦІЯ ФАГОЦИТАРНОЇ ЛАНКИ ІМУНІТЕТУ ПРИ ЗАСТОСУВАННІ ПРИРОДНОГО ГЕПАТОПРОТЕКТОРУ В КОМПЛЕКСНОМУ ЛІКУВАННІ ХВОРИХ НА ТУБЕРКУЛЬОЗ ЛЕГЕНЬ З ПОБІЧНИМИ РЕАКЦІЯМИ НА МЕДИКАМЕНТИ

Various types of adverse reactions to medications often occur during the treatment of diseases that require the simultaneous administration of several drugs. Methods. To study the effect of the natural hepatoprotector Hepatomunil on immunological and biochemical blood parameters, there was a clinical and laboratory examination of 20 adult patients with pulmonary tuberculosis with a deviation from the norm of at least one blood test of the liver or kidneys function during antituberculosis treatment. Biochemical and immunological research methods were used. The drug Hepatomunil was prescribed in the second month of standard four-component anti-tuberculosis therapy for 20 days. Results. There was a significant decrease in blood levels of cytolytic enzymes AST and ALT after the course of treatment with Hepatomunil which showed an effective hepatoprotective action. The phagocytic number of blood granulocytes increased significantly from (6.3 ± 0.6) units up to (11.2 ± 2.1) units; and the one of blood monocytes did from (6.8 ± 0.7) units up to (11.1 ± 1.7) units also. The drug had no effect on the studied parameters of cellular immunity (CD3+19–, CD4+8–, CD4–8+, CD3–16+, CD3–19+). Conclusions. The drug Hepatomunil demonstrated not only pronounced hepatoprotective, but also immunomodulatory properties when used in the complex therapy of patients with pulmonary tuberculosis. It stimulated the blood phagocytes function by restoring their ingesting capacity (with an increase of the phagocytic number), which is very important in the treatment of patients with chronic lung diseases with infectious agents involved, which are destroyed better when the phagocytic function of blood cells is activated. Key words: immunomodulator, hepatoprotector, hepatotoxic reactions, phagocytosis, pulmonary tuberculosis