mohammad sharifzadeh

MicroRNAs expressions that are known as Posttranscriptional repressors of gene expression in animals and plants have an important role in diabetic consequences and pathogenesis. This research aimed to investigate the expression of miR-34a, miR-126, and miR-125a-5p levels for diagnosis of diabetes, and the effect of α-L-guluronic acidand β-D-mannuronic acid supplementation on expression patterns of these MicroRNAs in diabetic rats.

Total MicroRNAs levels were measured by Quantitative reverse transcription polymerase chain reaction (qRT-PCR) method. Body weight, fasting insulin level, food intake and Vitamin D level in four groups were also assessed after 4 weeks.

The analyses illustrate marked declines in expression of miR-126 (p=0.009) and miR-125a-5p (p=0.019) levels in the control diabetic group when compared to the control healthy group. Expression levels of miR-126 (p=0.026) and miR-125a-5p (p=0.041) were upregulated considerably in diabetic rats after treatment with β-D-mannuronic acid and α-L-guluronic acid, respectively.

These results suggest that use of miR-126 and 125a-5p is a sensible criterion for diagnosing diabetes. β-D-mannuronic acid is also considered a new therapeutic agent to correct disturbances in the MicroRNAs profile of diabetic rats.

Sleep disorders are common in industrialized and developing societies. This study aimed to investigate the sleep-inducing potential of Carthamus tinctorius L. (safflower) fractions and purified components on insomnia based on Iranian traditional medicine references.

The methanol extract of safflower petals and the hexane, ethyl acetate, and methanol fractions were prepared. Additionally, a Carthamus red pigment fraction was obtained through alkaline extraction (with sodium carbonate) and acidic precipitation (with citric acid). The red pigment fraction was further isolated using semi-preparative high-performance liquid chromatography. The hypnotic activity of these fractions and purified compounds was assessed using the pentobarbital-induced loss of righting reflex test.

Both the ethyl acetate and red pigment fractions at 200 mg/kg demonstrated significant hypnotic activity compared to the control group. In contrast, hexane and methanol fractions showed no significant effects at 200 mg/kg. The hypnotic effect of the red pigment fraction was dose-dependent (100, 150, 200 mg/kg). Purification resulted in three major compounds: EEE (1), EZE (2), and EZZ (3), isomers of N1, N5, N10-tri-p-coumaroylspermidine, which exhibited significant hypnotic activity at 15 mg/kg, antagonized by flumazenil (2 mg/kg).

Our findings suggest that safflower extract exhibits a dose-dependent hypnotic effect, with tri-p-coumaroylspermidine identified as the primary active compound. This activity is at least partly linked to gamma-aminobutyric acid (GABA) receptors. However, further investigation is needed to elucidate the underlying mechanism and potential side effects.

Urtica pilulifera L. seed (UPS) is a Persian traditional medicine prescription that positively affects female infertility.

This study aimed to evaluate the beneficial effects of UPS on a diminished ovarian reserve (DOR) model induced by cyclophosphamide in Balb/c mice.

A single intraperitoneal (75 mg/kg) of cyclophosphamide was administered to establish a DOR model. 25 female Balb/c mice (6-8 wk, 25 ± 2 gr) were randomly divided into 5 groups (n = 5/each), including control (normal saline), model (DOR), DOR+50, DOR+100, and DOR+200 (mg/kg UPS, gavage) groups for 14 days. The levels of follicle-stimulating hormone, luteinizing hormone, estradiol, malondialdehyde, superoxide dismutases, apoptosis, and histopathological alterations were analyzed. Gas chromatography-mass spectrometry analysis performed to identify the phytochemicals of the UPS.

It was observed that the UPS extract reduced malondialdehyde concentration and apoptosis in the DOR model as well as enhanced superoxide dismutases activity in the ovaries in a dose-dependent manner. Moreover, it exerted a modulatory effect on steroidal hormones such as follicle-stimulating hormone, luteinizing hormone, and estradiol. The histopathological analysis revealed the therapeutic potential of the UPS extract. The main chemical components of UPS were linoleic acid (59.25%), n-hexadecanoic acid (10.36%), and oleic acid (8.29%).

The results indicated that the UPS extract has therapeutic potential in the DOR model. This potential is attributed to the reduction of oxidative stress, modulation of apoptosis, and regulation of steroidal hormones that may be associated with the observed beneficial effects of fatty acids on fertility improvement

Pseudomonas aeruginosa is an important pathogen in healthcare settings that poses significant challenges due to its ability to rapidly develop antibiotic resistance. Its propensity to form biofilms and adapt to host defenses makes it even more difficult to treat, leading to prolonged and debilitating illnesses. So, it is vital to prioritize efforts to develop new strategies for treating infections caused by this pathogen. In the present work, morphological and biological characteristics of vB_PaeS_TUMS_P6 (P6), a lytic phage against P. aeruginosa, belonging to the genus Luzseptimavirus were fully described.

P. aeruginosa ATCC 27853 was used for propagation and biological characterization of P6. Its morphology was assessed using transmission electron microscopy (TEM). Adsorption rate assay, one-step growth curve analysis and time-kill experiment were analyzed. Host Range of P6, as well as pH and thermal stability were also determined.

The results showed that it was of classic podovirus morphology and had a short latent period. It could kill bacteria at multiplicity of infection as low as 0.01 and also infect some multidrug-resistant clinical isolates. Stability data suggested that P6 remained stable in various temperatures and pH levels, which is a beneficial characteristic for phage therapy in different situations.

This study presents promising data supporting the future use of P6 as a candidate for phage therapy.

In Traditional Persian Medicine (TPM) saffron is used as an accompaniment agent “Mobadreq” in poly herbal formulations. According to TPM texts, “Mobadreq” is a substance (or drug) which facilitates access of drugs or food to the whole body or specific organs. This study investigated the effect of oral co-administration of Crocus sativus L. (saffron) on the absorption and some pharmacokinetic parameters of acetaminophen in rats. Two groups of Rats (n=6) were treated by 1: acetaminophen 10 mg/kg along with Crocus sativus 4 mg/kg (test group) and 2: 10 mg/kg acetaminophen (control). The plasma concentrations of acetaminophen after oral administration (at 0, 5, 10, 15, 20, 40, 60, 90, and 120 min) were monitored by an HPLC-UV method. Results indicated that the plasma concentration of acetaminophen in the test group was reached to the maximum concentration (Cmax) faster than control group. As a result, at 5 to 40 minutes after drug gavage, the concentration of acetaminophen in both groups was significantly different.  It was also found that co-administration of acetaminophen and saffron significantly increased acetaminophen’s area under concentration curve (AUC0-60) in compare to the acetaminophen alone (p<0.025). These results suggested that saffron could increase absorption rate of acetaminophen. Consequently, saffron can be considered and introduced as an enhancer of absorption rate and efficacy of acetaminophen and other drugs at least by oral route although the drug interactions with this herb should be considered.

Several vaccine-induced thrombotic thrombocytopenia syndrome (VITTS) cases have been reported after the ChAdOx1 nCov-19 vaccination. The current study systematically reviewed the reported post-ChAdOx1 nCoV-19 vaccination thrombotic thrombocytopenia cases. Their laboratory and clinical features, as well as the diagnostic and therapeutic measures, were investigated. Online databases were searched until 25 August 2021. Studies reporting post-ChAdOx1 nCov-19 vaccination thrombotic thrombocytopenia syndrome (TTS) were included. Overall, 167 cases (21-77 years old) from 53 publications were included showing a female dominance of 1.75 times. About 85% of the cases exhibited the primary symptoms within the first two weeks post-vaccination. Headache was the most common initial symptom (>44.2%), and hemorrhage/thrombotic problems (22.46%), as well as discoordination/weakness/numbness/ hemiparesis/cyanotic toes (19.6%), were the most prevalent uncommon initial symptoms. Prothrombin time (PT), D-dimers, and C-reactive protein were the most remarkable increased laboratory parameters in 50.6%, 99.1%, and 55.6% of cases, respectively. In comparison, platelet and fibrinogen were the most remarkable decreased laboratory parameters in 92.7% and 50.5% of cases, respectively. Most VITT cases presented with cerebral venous thrombosis/cerebral venous sinus thrombosis, supraventricular tachycardia, transverse sinus/cerebral thrombosis, pulmonary embolism, and cerebral hemorrhage. Anti-PF4 antibody measurement through immunoassays and functional assays were positive in 86.2% and 73% of cases, respectively. About 31% of the cases died. Early diagnosis and proper therapeutic measures are important in ChAdOx1 nCov-19 vaccine-induced VITTS patients. Therefore, experts are recommended to know the corresponding clinical and laboratory features, as well as diagnostic methods. Elucidation of the pathophysiologic mechanism of ChAdOx1 nCov-19 vaccine-induced TTS deserves further investigation.

 Paeonia daurica ssp. macrophylla (PD) (Paeoniaceae) is a perennial plant, growing in Iran. In Persian medicine, another species, Paeonia officinalis “Oode-saleeb” has been used especially for treating epilepsy and brain disorders. This study aimed to evaluate the sedative and hypnotic activity and the acute toxicity of P. daurica root extracts in mice. 

 Sedative and hypnotic effects of the aqueous extract, total hydro alcoholic 80% extract, and its fractions, hexane, chloroform, and methanol were examined by the righting reflex method. Plant samples (50, 100, and 200 mg/kg) and vehicle (10 mL/kg) were injected intraperitoneally (i.p.) 30 minutes before sodium thiopental injection (40 mg/kg, i.p.) in groups of seven mice. The time taken before losing the righting reflex and the time taken to regain the righting reflex were recorded as the onset of sleep and sleep duration, respectively. The findings of the study indicated that, with the exception of the chloroform fraction and the total hydroalcoholic extract administered at the dose of 50 mg/kg, all the samples demonstrated a reduction in sleep onset time produced by sodium thiopental. Furthermore, chloroform (200 mg/kg) was the most effective sample on sleep duration compared to diazepam (3 mg/kg) (p<0.001). 

 Results of this study demonstrated that Paeonia daurica root can be used as a sedative and hypnotic complementary drug.

This study aimed to assess the antinociceptive activity of extracts and fractions of Paeonia daurica subsp. macrophylla in BALB/c mice. Various doses of hydro-alcoholic extract (HE), hexane fraction (F-hexane), methanol (F-MeOH), and chloroform (F-CHCl3), as well as aqueous extracts (AE), were evaluated by a well-known model, a formalin-induced pain test in mice. All extracts, piroxicam 0.1 mg/kg, and negative control groups were administered 30 minutes before formalin injection. Flinching, licking, and biting reflexes were measured as painful factors compared with controls at intervals of 0 to 5 minutes, 0 to 15, and 0 to 60 minutes after formalin injection. The acute oral toxicity test of total ethanolic and aqueous extracts showed no signs of toxic effect up to a dose of 5000 mg/kg. In the formalin test at a time interval of 0 to 5 minutes, there was no significant difference between the results of the study groups. In the range of 0 to 15 minutes, the effect of AE (1 g/kg), HE (2, 3 g/kg), and F-hexane (1 g/kg) was significantly higher than the positive control group (p<0.01). In the time interval of 0 to 60 minutes as the total time of the experiment, the effect of AE (0.25 g/kg), AE (0.5, 1 g/kg), HE (2, 3 g/kg), F-hexane (1 g/kg) were significantly different than the positive control group. It can be concluded that extract of P. daurica ssp. macrophylla might be helpful in the treatment of pain in humans.

Vitamin K2 refers to a series of naphthoquinone derivatives, which have a variety of physiological and pharmacological functions for the human body. The most important type of vitamin K2 is menaquinone-7 (MK-7), an expensive raw material with no local manufacturers in Iran.

Since there was no report on the yield of MK-7 produced by the currently available Bacillus subtilis natto species in Iran, this study aims to optimize the culture condition for the production of MK-7 using this Bacillus species.

The base medium (BM) for MK-7 production contained glycerol (6.3%), soybean peptone (3%), and yeast extract (0.51%). The selected factors for optimizing the MK-7 production included the incubation temperature (30, 37, and 40°C) and incubation time (72, 96, and 120hr) with/without the addition of K2HPO4 to the fermentation medium. Three sets of experiments with six modes in each set were designed based on these parameters. MK-7 content was analyzed by the HPLC method.

Two experiments showed the highest MK-7 production yields of 0.319 and 0.3158 mg/L. The culture condition for both of these yields was as follows:120 hours incubation time in the presence of K2HPO4. However, the incubation temperature was different in these two experiments. The incubation temperature of 30°C resulted in 0.319 mg/L MK-7 concentration, and 37°C yielded 0.3158 mg/L.

B. subtilis natto (IBRC-M 11153) is suitable to be used as a basic platform for the mutation and production of a high-producer species. Optimizing the culture conditions using the wild-type species is not beneficial in increasing the production ability of the bacterium. It is necessary to use different methods for enhancing the production yield of MK-7 to lower the cost of microbial production and make the industrial process economic.

This corrects the article “Brain targeted delivery of rapamycin using transferrin decorated nanostructured lipid carriers published in 2022: Volume 12, Issue 1, Pages 21-32 (doi: 10.34172/bi.2021.23389). The original version of this article contained an error in Fig. 3. The confocal images for cellular uptake of coumarin-6 loaded bare NLCs (B-NLC), and transferrin decorated NLCs (Tf-NLC) after 2 hours incubation was mixed up and two different resolutions of the same specimen mistakenly named and reported unintentionally. This has now been corrected in the PDF and HTML versions of the article. Here the correct images are reported as below:

The Coronavirus disease 2019 (COVID-19) pandemic has affected more than 269 million worldwide, with more than five million deaths as of early December 2021. The main concerns in this pandemic include the asymptomatic nature of COVID-19, leading to the infection of many healthy people, the infectious nature of the pathogen, and its high spreading rate. The disease features have highlighted the importance of controlling this pandemic via vaccines. There has been a worldwide race to produce better, more protective, and efficacious vaccines. Simultaneously, different new variants of the virus are emerging. Therefore, there is a concern about the efficacy of the vaccines against new variants. The platform used for COVID-19 vaccine development needs to be flexible enough to enable the manufacturer to react suitably to new virus variants. We performed a comprehensive search in the online databases of PubMed, Scopus, Google Scholar, clinicaltrials.gov, WHO, ICTRP, and Cochrane until December 10th, 2021. There are 331 candidate vaccines in clinical development, with 194 in the preclinical stage and 137 in different clinical phases. Eleven platforms have been used for the development of COVID-19 vaccines, including inactivated/live attenuated virus, protein subunit, virus-like particle (VLP), non-replicating/replicating viral vectors (VVnr or VVr), VVr or VVnr plus antigen-presenting cell, bacterial antigenspore expression vector, DNA, and RNA. The VLP-based vaccine platform is a safe, highly immunogenic, and flexible platform for developing vaccines. This review focuses on VLP-based vaccine platforms and explicitly discusses the six VLP-based COVID-19 vaccines in clinical trial phases.

Recent studies showed that rapamycin, as a mammalian target of rapamycin (mTOR) inhibitor, could have beneficial therapeutic effects for the central nervous system (CNS) related diseases. However, the immunosuppressive effect of rapamycin as an adverse effect, the low water solubility, and the rapid in vivo degradation along with the blood-brain barrier-related challenges restricted the clinical use of this drug for brain diseases. To overcome these drawbacks, a transferrin (Tf) decorated nanostructured lipid carrier (NLC) containing rapamycin was designed and developed.

Rapamycin-loaded cationic and bare NLCs were prepared using solvent diffusion and sonication method and well characterized. The optimum cationic NLCs were physically decorated with Tf. For in vitro study, the MTT assay and intracellular uptake of nanoparticles on U-87 MG glioblastoma cells were assessed. The animal biodistribution of nanoparticles was evaluated by fluorescent optical imaging. Finally, the in vivo effect of NLCs on the immune system was also studied.

Spherical NLCs with small particle sizes ranging from 120 to 150 nm and high entrapment efficiency of more than 90%, showed ≥80% cell viability. More importantly, Tf-decorated NLCs in comparison with bare NLCs, showed a significantly higher cellular uptake (97% vs 60%) after 2 hours incubation and further an appropriate brain accumulation with lower uptake in untargeted tissue in mice. Surprisingly, rapamycin-loaded NLCs exhibited no immunosuppressive effect.

Our findings proposed that the designed Tf-decorated NLCs could be considered as a safe and efficient carrier for targeted brain delivery of rapamycin which may have an important value in the clinic for the treatment of neurological disorders.

The purpose of this study was to evaluate the effects of ATRA (all trans retinoic acid), vitamin D3, and their combination on circulating levels of miR (MicroRNA) -125a-5p, miR-126, and miR-34ain diabetic rats.

Total miRNA was extracted from plasma samples. miRNA expression profiles of 30 rats in five groups were analyzed after 4-week intervention. The expression levels of miRNAs were measured using qRT-PCR.

We analyzed the expression of miR-126, miR-125a-5p, and miR-34a in serum among all five groups (p=0.268). The levels of miRNA-126 (p=0.004) and miR-125a-5p (p=0.014) showed a significant difference among our experimental groups. The circulating levels of miR-126 decreased in DC (Diabetic control) group compared to the HC (Healthy control) group (p=0.009). In addition, vitamin D3+ATRA supplementation increased miR-126 expression (p=0.014). Moreover, the levels of miR-125a-5p decreased in the DC group compared to the HC group (p=0.019).

The expression of miR-126 and miR-125a-5p decreased in diabetic rats. Also, vitamin D3+ATRA can be considered a new therapeutic agent that can elevate miR-126 expression and prevent diabetes-related cardiovascular complications.

Excessive exposure to the sources of fluoride in drinking water, oral care products, and food is a widespread problem. Fluoride is associated with impairment in child intelligence development. It causes DNA damage, oxidative stress, and mitochondrial dysfunction, mainly due to the production of reactive oxygen species (ROS). It has been postulated that the use of antioxidants such as astaxanthin, may alleviate fluoride’s adverse effects. This study assessed the effects of fluoride on cellular ROS content and rat’s learning and memory ability and investigated the protective potency of astaxanthin with emphasis on the role of glutamate using the Morris Water Maze test, glutamate concentration determination, and western blot techniques. The fluoride treatment of cells results in an increment of cellular ROS, whereas astaxanthin inhibits lipid peroxidation. Fluoride significantly decreases the cellular glutamate uptake and glutamate transporter, protein level, possibly due to the disruption of mitochondrial energy metabolism and defect of the transporter recycle, respectively. The in-vivo study indicated that the treatment of rats with fluoride led to a loss of learning, while astaxanthin improved memory dysfunction. Measurement of ROS and glutamate levels of rat brain hippocampus showed that fluoride increased the ROS but decreased the glutamate. On the other hand, the utilization of astaxanthin decreased the brain ROS content and increased the glutamate level. It seems that fluoride disrupts the normal function of neurons via increment of ROS production and decrement of glutamate level, whereas astaxanthin has neuroprotective potency due to the ROS scavenging ability.

Eryngium caeruleum (Apiacea) is native to the northern forests of Iran. The anti-diabetic effect of other species of the genus Eryngium has already been reported in previous studies. In this study, the anti-diabetic effect of this extract on animal blood lipid factors was investigated. Hydroalcoholic extract was obtained from different parts of the plant, including roots, leaves, and aerial branches with fruits were prepared by maceration with 70% ethanol. Oral acute toxicity of the extracts was assayed in different doses of 2000, 4000, and 8000 mg/kg in rats. To induce diabetes in the studied animals, 60-70 mg/kg of streptozotocin (STZ) was injected intraperitoneally (IP). For the purpose of this study, 72 male Wistar rats were randomly divided into different groups of normal, diabetic, and positive controls (metformin 500 mg/kg) as well as 9 diabetic groups that orally received 200, 400, and 800 mg/kg of extracts. The effects of the treatment with extracts for a 14-day period were investigated on weight, blood glucose, and lipid profile. By comparing the control groups with the groups of hydroalcoholic extracts of E. caeruleum showed that the most effective sample on weight gain and also on reducing blood glucose was the group receiving 800 mg/kg of the aerial branches extract (P < 0.01 and P < 0.001, respectively) after 14 days. As well, the most effective sample on lowering the blood lipid factors was the hydroalcoholic extract of the root of E. coareleum with a dose of 200 mg/kg, which showed a significant effect on lowering total cholesterol in diabetic rats compared to the diabetic controls (P < 0.05). Hydroalcoholic extract of leaves with 200 mg/kg also showed a better effect on lowering the LDL and VLDL levels compared to the diabetic control group (P < 0.001). The results of pancreatic histology in the samples showed that the extracts of the aerial branch and root (800 mg/kg) had significant effects on the regeneration of the islets of Langerhans compared to the diabetic control group. In conclusion, E. caeruleum could significantly improve glycemic and lipid profiles in diabetic rats.

Considering that hemorrhagic stroke patients are at higher risk for bleeding, administration of higher doses of melatonin with a controversial coagulation profile is a serious concern. 

This study aimed to investigate the possible effects of high doses of melatonin on bleeding parameters and blood hemostasis in hemorrhagic stroke patients. 

This study is a randomized, double-blind, prospective, controlled trial. Confirmed hemorrhagic stroke patients were divided into two groups. Participants were randomly assigned into the melatonin group (30 mg daily via gastric tube gavage for 5 consecutive days) or the control group. Each patient was monitored for 5 days, and 2 blood samples were taken and the effect of the intervention on coagulation factors and blood hemostasis were investigated. 

In total, 30 patients were randomly assigned to melatonin (n=15) or control groups (n=15). there was no significant difference between the two groups in demographic and clinical characteristics. There was a significant decline in prothrombin time (PT) and fibrinogen levels in the melatonin group (p=0.011 & p<0.001, respectively). P-values for VII and VWB factors showed a significant increment in these two factors in the melatonin group after the intervention (p=0.035 & p=0.002, respectively). No significant changes in serum levels of D-dimer factor, APACHE II, and GCS scores were evident in the two groups after the intervention (p>0.05). 

Considering the favorable changes in coagulation parameters observed in this study, it could be concluded that melatonin can have both procoagulant and antithrombin properties.

Malnutrition is an acute or a chronic condition resulting from an imbalance in the intake, both in the form of undernutrition and over nutrition, leading to changes in the composition or reduced function of the body. Bio-social conditions and acute or chronic diseases are the most important factors affecting nutrition. It has been suggested that awareness of the prevalence and severity of malnutrition in hospitalized patients can be used by managers to understand the causes, health care system requirements, and health plans.

Medical records of 483 patients from 11 different wards of Shariati general hospital were assessed to evaluate the quality of nutritional assessment and the rate of referral to nutrition experts by physicians. This study consisted of two phases: evaluation of initial nutritional assessment and assessing the accuracy of malnutrition screening forms completion.

Our study showed no initial nutritional assessment for 34% of the patients. Assessment of the accuracy of malnutrition screening showed that there was a considerable error in the reporting of BMI (66%), weight loss (51%), appetite loss (50%), and severity of the patient’s situation (39%). Also, the rate of referral to a nutritionist was 0% and 1% in the first and second phases of the study, respectively.

The present study showed that the quality of nutritional screening and subsequent referral to nutrition experts for professional nutritional assessment is negligible in Shariati hospital, Tehran, Iran.

Dementia is a disease in which memory, thinking, and cognitive skills are impaired, with Alzheimer’s being the most common type of dementia. Brassica nigra is useful for eliminating memory loss in traditional Persian medicine. This study aims to examine the effect of B. nigra fixed oil (BNO) on the changes in memory caused by β-amyloid.

This research was conducted on 42 Wistar rats divided into 7 groups (n=6) including 1) control (received vehicle), 2) the group receiving BNO (925 and 462.5 mg/kg), 4) sham group 5) Alzheimer group (receiving 50 ng/µl/side β-amyloid in CA1 area of hippocampus) and 2 groups receiving β-amyloid along with two different doses of BNO. The daily gavage of BNO was done 2 to 21 days post amyloid injection. The spatial memory was evaluated in Morris water maze from day 21 to 26.

The results of this study revealed that the gavage of BNO (925 mg/kg) to rats receiving β-amyloid, as compared to those receiving β-amyloid alone, significantly decreased the traveled distance and the required time for finding hidden platform on the training days and increased the time of presence in the target quadrant on the test days. The analysis of BNO with GC-MS revealed that Erucic acid (24.79%) and 11-Eicosenoic acid (17.23%) had the highest content in the BNO.

Regarding the presence of unsaturated fatty acids, it is likely that the consumption of BNO can play an important role in the prevention of memory degradation which warrants further clinical studies.

Although mechanical ventilation is frequently a life‑saving therapy, its use can result in unwanted side effects. It has been well documented that the choice of sedating agent may influence the duration of mechanical ventilation. Melatonin is a sedative and analgesic agent without any respiratory depressant effect which makes it an attractive adjuvant for sedation in the intubated patients. The aim of this study is to evaluate the effect of melatonin on the duration of mechanical ventilation in patients with hemorrhagic stroke.

Forty adult intubated patients with hemorrhagic stroke, who were admitted to the Intensive Care Unit (ICU) within 24 h of onset, were enrolled in this randomized double‑blind study. Subjects in the melatonin group received 30 mg of melatonin every night throughout the nasogastric tube. Length of ICU stay, mortality, and duration of mechanical ventilation were recorded for all patients.

The duration of mechanical ventilation and length of ICU stay were shorter in patients who received melatonin in comparison with the control group, and this difference was statistically significant for the length of ICU stay and marginally significant for the duration of mechanical ventilation. Although not statistically significant, the mortality rate of the control group was 30%, almost double that of the study group (15%).

Melatonin possesses hypnotic, analgesic, anti‑inflammatory, and anti‑oxidative properties that distinguish it as an attractive adjuvant in patients under mechanical ventilation. In conclusion, the administration of melatonin may facilitate the weaning process through decreasing the consumption of sedatives with respiratory depressant properties as well as preventing ventilator‑associated lung injury

Polygonatum orientale, an herbaceous and perennial plant from family Asparagaceae, is native to the forests of northern Iran. The hypoglycemic effects of other species of the Polygonatum have been proven.

The aim of this study was to evaluate the hypoglycemic effect of P. orientale rhizome extract and its effects on the antioxidant enzymes in the plasma of the normal and streptozocin induced diabetic rats.

30 male rats were divided into 6 groups; healthy control, negative control, positive control (metformin, 500 mg/kg) and three groups of diabetic rats (200, 400 and 800 mg/kg) that received the ethanolic (70%) extract orally. After 28 days effects of the extract on blood glucose, superoxide dismutase (SOD) and catalase enzymes, as well as total antioxidant capacity of the plasma (by FRAP test) were investigated.

According to the results, the percentage of reduction in blood glucose in the groups of 400 (2%) and 800 (25%) mg/kg compared to the diabetic control group was significantly different, (P<0.05) and (P<0.001), respectively. The difference in blood glucose levels between 400 and 800 mg/kg and metformin was not significant (P>0.05). Also, 200 and 400 mg/kg of the extract reduced the amount of SOD in the plasma comparable to the normal group.

It can be concluded that the ethanolic extract of rhizome of P. orientale exhibits a significant hypoglycemic effect that may be related to the presence of steroids, flavonoids and polysaccharides.

Increasing the number of students in universities, simultaneously limiting allocation of funds to them, and maintaining the highest efficiency level in education and research are of paramount importance. There are several methods to assess the efficiency of universities, and one of the most widely used of which is data envelopment analysis (DEA). The aim of this study was to determine the input and output criteria to evaluate the efficiency of universities of medical sciences through review-related articles using the DEA method.

The time limit for retrieving articles was considered from the beginning of the publication of the first paper in this field until the end of 2017. The data were retrieved from Web of Science, Scopus, Ovid, ProQuest, Science Direct, and PubMed using advanced searches. Inclusion criteria were as follow: relevancy of the articles to the purpose of the research, availability of the articles’ full-text, articles published to the end of 2017, and articles published in English.

The most inputs used in the literature to determine university efficiency were number of academic staffs, budget and costs, number of students, number of nonacademic staffs, spaces, and equipment and studentchr('39')s entrance scores. Also, the most outputs used in the literature to determine university efficiency were number of graduates, publications, incomes, number of students, and studentchr('39')s scores.

This study showed that a large number of researchers have focused on measuring and comparing the efficiency of universities to improve efficiency, reduce costs, and manage the resources. Efficiency analysis by DEA allows the policymakers to define and develop policies and guidelines to improve their performances.

While traumatic brain injury (TBI) is a predisposing factor for development of post-traumatic epilepsy (PTE), the occurrence of seizures following brain trauma can infuriate adverse consequences of brain injury. However, the effect of seizures in epileptogenesis after mild TBI cannot yet be accurately confirmed. This study was designed to investigate the histopathological and molecular modifications induced by seizures on traumatized brain. Using a new method, head was traumatized and seizures were evoked by sub-convulsive dose of pentylenetetrazole (PTZ) fifteen days after induction of focal mild TBI. Convulsion assessments were performed one hour after PTZ injection and was followed by histopathological and molecular evaluations. A significantly higher score and longer duration of seizure attacks as well as higher number of epileptiform discharges were observed in the TBI+PTZ group compared to sham and TBI groups. An elevated number of apoptotic cells was observed in the TBI+PTZ group compared to sham and TBI rats. Molecular investigations revealed higher levels of Bax/Bcl2 ratio, Caspase 3, and NF-κB in the TBI+PTZ group compared to the other animal groups. The value of Nrf2 did not change after mild TBI compared to sham and PTZ control groups. Occurrence of seizures after TBI, however, significantly decreased the level of Nrf2. Our data indicated that seizure occurrence following mild TBI aggravates cell injury and death via activation of neuroinflammatory processes and may increase the risk of PTE. Additionally, our results suggest a potential protective role of Nrf2 after chemically evoked PTE.

Regarding the importance of new treatments to control and treat multiple sclerosis (MS), in this study we investigated the role of Benzoaric acid (BA) on the neuro-inflammation and apoptosis processes in the cuprizone (cup)-induced animal model of MS. In this experimental study, 35 males C57BL/6 mice were divided into five groups. The study groups were included, control: received six weeks of normal powdered food beside intraperitoneal (i.p.) injection of BA solvent (100 µL per day PBS) for the last two weeks, cup: received six weeks of powdered food contains 0.2% cup beside i.p. injection of BA solvent for the last two weeks and cup-treatment: received six weeks of powdered food contains 0.2% cup beside i.p. injection of 20, 40 and 80 mg/kg BA for the last two weeks. Eventually, the medial corpus callosum area of the animal’s brain was evaluated via western blot and Real-Time PCR methods.  Ethical points were observed according to the declaration of Helsinki and relevant code of ethics, regarding minimizing harms during animal experimentation (UOZ-GR-9517-13). Molecular studies have shown that BA-80 decreased mRNA (p <0.01) and protein expression of NF-KB and consequently increased I-KB/NF-KB ratio (p <0.05) and decreased inflammation in compare to cup group. Moreover, BA-80 decreased caspase-9 mRNA (p<0.01) and caspase-8 mRNA (p <0.05) and subsequently increased caspase-8/caspase-9 ratio (p<0.01) and decreased apoptosis in compare to cup group. The dose of 80 mg/ml BA via decreasing cup-induced neuro-inflammation and neuro-apoptosis has protective effects in this model.

Here we aimed to comprise several histological methods to determine the most accurate technique for evaluation of efficacy of neuroprotective agents in animal model of multiple sclerosis (MS).

Male C57BL/6 mice were treated for 6 weeks in control, control + Benzoraic acid (BA, as neuroprotective agent) 20, 40, 80 mg/kg during last 2 weeks, Cuprizone (0.2%) as demyelinating agent, and Cuprizone (0.2%) + BA (20, 40, 80 mg/kg during last 2 weeks) groups. At the end of experiment, histological examinations including immunohistochemistry (IHC), Hematoxylin & Eosin (H & E) staining, Luxol Fast Blue (LFB) staining, and Transmission Electron Microscopy (TEM) techniques were performed for evaluation of myelin damages.

Significant myelin damage was detected by all of the used histological methods in Cuprizone group (p < 0.001 compared to control group). LFB technique could not show improvement in damages by all doses of BA. The H&E, IHC and TEM methods showed significant protective effects of the high BA dose compared to Cuprizone group. Only the TEM method could show significant (p < 0.05) protective effect of the medium BA dose.

TEM was the most and LFB was least sensitive methods. Present study suggests simultaneous using of methods such as H & E for better assessment of neuroinflammation and IHC for confirmation of TEM results. Moreover, in the case of restriction in methods, TEM and IHC are the most sensitive methods and could provide reliable results related to efficacy of neuroprotective agents in this model.

One of the most frequent complications of diabetes is diabetic peripheral neuropathy. Hyperglycemia would result in the advancement of this condition over a period of time. The most effective way in preventing diabetic neuropathy is regular control of glucose. In this study; we evaluated the effects of lithium onstreptozocin (STZ)-induced diabetic neuropathy in rats. Diabetic neuropathy was created 7 weeks after administration of STZ (45 mg/kg). Lithium was added to drinking water (450 mg/l) for 7 weeks and its plasma level after this period of time was 0.17±0.02 mmol/l. Levels of adenosine triphosphate (ATP) in dorsal root ganglion (DRG) neurons, oxidative stress parameters, open-field activity test and morphological analysis were assessed in this investigation. Currentresults showed significant elevation of oxidative stress biomarkers, reduction of ATP, abnormal morphology of DRG neurons and decrease of total distance moved in rats with STZ-induced diabetic neuropathy. The alterations in mentioned parameters were considerably restored by lithium treatment. These findings provide evidence for protective effects of lithium on STZ-induced diabetic neuropathy.