Reza Heidari

Abstract
Aim
To describe the epidemiological and clinical characteristics along with outcomes of hospitalized Coronavirus Disease 2019 (COVID-19) patients with and without diabetes.

Methods
This retrospective, single-center study included 595 consecutive hospitalized patients with confirmed COVID-19 at Baqiyatallah Hospital in Tehran, Iran, from February 26, 2020 to March 26, 2020. Demographic data, clinical, laboratory, and radiological findings were collected and compared between patients based on diabetes status. Complications and clinical outcomes were followed up until April 4, 2020.

Results
From among the 595 hospitalized patients with COVID-19, the median age was 55 years and 401 (67.4%) were male. The most common symptoms included fever (419 [70.4%]), dry cough (368 [61.8%]) and dyspnea (363 [61%]). A total of 148 patients (24.9%) had diabetes, and compared with patients without diabetes, these patients had more comorbidities (eg, hypertension [48.6% vs. 22.3%; P < 0.001]); had higher levels of white blood cell count, neutrophil count, C-reactive protein, erythrocyte sedimentation rate and blood urea nitrogen, and had a higher proportion of patchy ground-glass opacity in chest computed tomography findings (52.7% vs. 25.7%; P < 0.001). Significantly, patients with diabetes had more complications and needed more respiratory support than those without diabetes (P < 0.001). At the end of the follow-up, treatment failure and death was significantly higher in patients with diabetes compared to those without diabetes (17.8% vs. 8.7%; P = 0.003).

Conclusion
COVID-19 patients with diabetes are at a higher risk of complications and a higher in-hospital mortality during hospitalization. Diabetes status of COVID-19 patients and frequent monitoring of glycemia would be helpful to prevent deteriorating clinical conditions.

Wound healing is known as one of the most complicated biological processes for injured skin caused by surgical, trauma, burns, or diabetic diseases, which causes a nonfunctioning mass of fibrotic tissue. Recent reports have suggested that exosomes (EXOs) secreted by this type of stem cells may contribute to their paracrine effect. In this study, the EXOs were isolated from the supernatant of cultured adipose‐derived stem cells (ADSCs) via ultracentrifugation and filtration. The EXO loaded in the alginate‐based hydrogel was used as a bioactive scaffold to preserve the EXO in the wound site in the animal model. The physical and biochemical properties of EXO loaded Alg hydrogel were characterized and results proved that fabricated structure was biodegradable and biocompatible. This bioactive wound dressing technique has significantly improved wound closure, collagen synthesis, and vessel formation in the wound area. Results offer a new viewpoint and a cell‐free therapeutic strategy, for wound healing through the application of the composite structure of EXO encapsulated in alginate hydrogel.

The aim of our study was to investigate mechanisms of aminoglycoside resistance in extended-spectrum beta-lactamases (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) isolates from Iran. To this end, 154 clinical isolates of K. pneumoniae were collected from two hospitals in Ilam city, Iran. The Kirby-Bauer (agar diffusion) antibiotic testing method was used to determine the susceptibility pattern of the isolates against kanamycin, gentamicin, tobramycin, netilmicin and amikacin. Aminoglycoside acetyltransferases (aac(3)-IIa, aac(6’)-Ib, and aac(3)-Ia), 16SrRNA methylase genes (armA and rmtB) and ESBL genes (blaTEM, blaSHV, and blaCTX-M) were detected by PCR amplification. 59.1% (n = 91) of K. pneumoniae isolates were detected ESBL producers with the phenotypic test. Moreover, blaTEM, blaSHV and blaCTX-M were detected in 83.5% (n=76), 52.7% (n=48) and 26.4% (n=24) of the ESBL-producing isolates, respectively. Among 52 resistant or intermediate isolates against aminoglycosides, the aac(3)-IIa, aac(6’)-Ib and rmtB genes were detected in 55.8% (n = 29), 80.8% (n = 42) and 1.9% (n = 1) of the isolates, respectively; none of the isolates, however, had the aac(3)-Ia and armA genes. Therefore, the results showed the high prevalence of aminoglycosides resistance in the K. pneumoniae isolates. As observed, the acetyltransferase modifying enzymes (aac genes) played major roles in determining this resistance. However, the rate of 16srRNA methylase genes was extremely low in K. pneumoniae.

Obsessive–compulsive disorder (OCD) is an important neuropsychiatric disorder worldwide. Common treatments of OCD include serotonergic antidepressants, which can cause potentially serious side effects. We assessed the effects of Lactobacillus casei (L. casei) Shirota consumption in an animal model of OCD. OCD-like symptoms were induced in rats by the chronic injection of the D2/D3 dopamine agonist quinpirole hydrochloride. Rats were classified into five groups of 6 rats. Four groups were injected chronically with quinpirole (0.5 mg/kg, twice weekly for 5 weeks). They were fed with L. casei Shirota (109 CF/g, daily for 4 weeks) (group 1), fluoxetine (10 mg/kg, daily for 4 weeks) (group 2), combination of L. casei Shirota and fluoxetine (group 3), and normal saline (positive control group). The last group did not receive dopamine agonist and was only injected with saline (negative control group). Expression levels of brain-derived neurotrophic factor (Bdnf), solute carrier family 6 member 4 (Slc6a4), and 5-hydroxytryptamine receptor type 2A (Htr2a) were assessed in orbitofrontal cortex tissues of all rats. Behavioral tests showed improvement of OCD signs in rats treated with L. casei Shirota, fluoxetine, and a combination of drugs. Quantitative PCR analysis showed a remarkable decrease in the expression of Bdnf and an increase in the expression of Htr2a in quinpirole-treated rats. After treatment with L. casei Shirota and fluoxetine, the expression level of Bdnf was increased remarkably, whereas Htr2a expression was decreased. The current study showed the effectiveness of L. casei Shirota in the treatment of OCD in a rat model. The beneficial effects of this probiotic are possibly exerted through the modulation of serotonin-related genes expression.

Oligonucleotide aptamers are short, synthetic and single-stranded DNA or RNA molecules capable of binding to a wide range of molecules, from small molecules to large cells. Nowadays, aptamers are valuable tools in research, clinical diagnosis and treatment. Their small size and high specificity in addition to their lack of immunogenicity make them great alternatives to other diagnosing candidates such as antibodies. In this study, we have introduced a new method based on competitive Enzyme-Linked Aptamer Sorbent Assay (ELASA) using single-stranded DNA (ssDNA) aptamers to measure cystatin-c levels in serum samples. To this aim, through a Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process a number of aptamers were selected from which an aptamer with a Kd (dissociation constant) value of 65.5 ± 0.007 nM was chosen for further analyses. The limit of detection (LoD) was found to be 216.077 pg/ml. The results of the analytical application of this method in serum samples were comparable to those of commonly used commercial kits.

Introduction Circulating tumor DNA (ctDNA) as a non-invasive marker that can provide more information on genetic and epigenetic alterations in tumor cells. The epigenetic modifications occur in the early stages of cancer, thus, it is considered as a target for early detection and prevention. The current study is to develop a ctDNA-probe based technology using capture, enrichment and analysis of epigenetic markers for early detection of breast cancer (BC). Materials and Methods: ctDNA from 45 women with early stage breast cancer and 90 healthy women as control samples were isolated. Methylation analysis performed for 6 differential regions by MeDIP-Probe method and all of them were sequenced. The KLF9 gene used as an internal control for amplifying the regions despite Methylation status. Results: The methylation analysis presented significant differences in methylation of two regions RASSF1A and HOXA10 between BC patients and healthy samples. Methylation in the regions was higher in BC than control case (P<0.001). Conclusions: Combinations of multiple methylation regions or CpG Island improved the positive predictive value for breast cancer detection. Analysis of methylation pattern of ctDNA using probe-base technology with screening methods such as mammography in high-risk women leads to noninvasive early detection of breast cancer.

An ultrahigh sensitive, simple and reliable Electrochemiluminescence (ECL) immunosensor for selective quantification of p53 protein was designed according to the enhancement effects of AuNPs on ECL emission of CdS nanocrystals (CdS NCs). CdS NCs were immobilized on the glassy carbon electrode and AuNPs introduced to the process through formation of a sandwich-type immunocomplex between first anti-p53/p53/ secondary anti-p53. ECL of CdS NCs firstly evoked the SPR of AuNPs which in return amplified the CdS NCs ECL intensity. By using graphene oxide in immunosensor fabrication procedure, and attaching more AuNPs on the surface of the electrode, the ECL intensity was further increased resulting in much higher sensitivity. After applying the optimum conditions, the linear range of the developed immunosensor was found between 20 and 1000 fg/ml with a calculated limit of detection of 4 fg/ml. Moreover, the interference, reproducibility and storage stability studies of the immunosensor were investigated. Finally, immunosensor's authenticity was evaluated by detecting the p53 protein in human spikes which offers it as a potential in early detection of cancer, monitoring the cancer progress and clinical prognosis.

ABSTRACT Psychrotrophes are organisms that thrive in cold environments. One of the strategies for their cold adaptation is the ability to synthesize cold-adapted enzymes. These enzymes usually display higher catalytic efficiency and thermolability at lower temperatures compared to their mesophilic and thermophilic counterparts. In this work, a psychrotrophic bacterial isolate, designated as SH3, was selected for the cloning of the gene encoding Pullulanase. Based on 16S rRNA gene sequence analysis, this isolate was identified as a species of the genus Exiguobacterium. Using degenerate primers designed based on sequence similarity, the partial sequence of the Pullulanase gene was PCR amplified. The sequence of the amplified fragment was determined and used for homology search using Blast program suite at NCBI. The results showed that the amplified fragment has maximum homology with a putative Pullulanase gene of Exiguobacterium sibericum. This promising result is going to be extended by future experiments using splinkerette PCR and Vectorret PCR technique to isolate the whole ORF coding for the expected Pullulanase gene.

ABSTRACT The aim of this work was to study the effects of cultural parameters on amylase production of Exiguobacterium sp. SH3. This bacterium produces an interesting cold-adapted amylase with high catalytic activity at temperatures approaching freezing condition. To this aim, the combinatorial effects of seven cultural parameters including: time (h), temperature(c), pH, shaking speed (rpm), yeast extract (g/l), tryptone (g/l), starch (%) were analyzed at two levels using Plackett–Burman design. The results indicated that the effects of 3 factors including temperature (25 and 40 °C), yeast extract (1 and 3 g/l), and shaking speed (100 and 180 rpm) were statistically significant resulting in improved amylase productions. Temperature at lower level while yeast extract and shaking speed at higher levels were more suitable for amylase production and secretion by this bacterium. The results revealed that cold condition is more suitable for amylase production by this psychrotrophic bacterium. Yeast as a general growth-improving factor and shaking as an important factor for aerobic organisms at higher levels were effective. The newly psychrophilic amylase SH3 seems to be suitable biocatalist for practical use in liquefaction of starch at low temperature, detergent and textile industries Key words: amylase, Exiguobacterium sp. SH3, psychrophilic

ABSTRACT Crohn&amp;amp;#39;s disease is a chronic relapsing inflammatory bowel disease that may affect any part of the gastrointestinal tract. The ileum, colon, and perineum are most commonly affected. It is characterised by transmural inflammation, and granulomata may be present. Whilst the etiology of Crohn&amp;amp;#39;s disease is not completely understood, it is thought to be caused by the complex interplay between genetic, immunological, microbiological, and environmental factors. Current opinion is that, in genetically susceptible individuals, there is an immune dysregulation to an environmental factor, and the intestinal microbiota plays a central role. Genetic studies of patients with Crohn&amp;amp;#39;s disease have found several gene mutations which a ffect the innate immune system. Two important mutations contributing towards the pathogenesis of Crohn&amp;amp;#39;s disease are Nucleotide-binding oligomerisation domain-containing protein 2 (NOD2) and autophagy-related 16-like 1 (ATG16L1). The most common symptoms o f Crohn&amp;amp;#39;s disease are diarrhoea, abdominal pain, weight loss, and fatigue. Symptoms reflect the site and behaviour of disease, and the presence or absence of strictures and fistulae. Extraintestinal manifestations may be present and typically affect the eyes, skin, joints, or liver. Investigations are performed to map the disease location, assess disease severity, and survey for complications of the disease or treatment. Management is with smoking cessation, steroids, immunomodulators, anti-tumour necrosis factor (TNF) therapy, or surgery.

ABSTRACT Carcinoma of the stomach is still the second most common cause of cancer death worldwide , although the incidence and mortality have fallen dramatically over the last 50 years in many regions. The incidence of gastric cancer varies in different parts of the world and among various ethnic groups. Despite advances in diagnosis and treatment, the 5-year survival rate of stomach cancer is only 20 per cent. Stomach cancer can be classified into intestinal and diffuse types based on epidemiological and clinicopath-ological features. The etiology of gastric cancer is multifactorial and includes both dietary and nondietary factors. The major diet-related risk factors implicated in stomach cancer development include high content of nitrates and high salt intake. Accumulating evidence has implicated the role of Helicobacter pylori (H. pylori) infection in the pathogenesis of gastric cancer. The development of gastric cancer is a complex, multistep process involving multiple genetic and epigenetic alterations of oncogenes, tumor suppressor genes, DNA repair genes, cell cycle regulators, and signaling molecules. A plausible program for gastric cancer prevention involves intake of a balanced diet containing fruits and vegetables, improved sanitation and hygiene, screening and treatment of H. pylori infection, and follow-up of precancerous lesions. The fact that diet plays an important role in the etiology of gastric cancer offers scope for nutritional chemoprevention. Animal models have been extensively used to analyze the stepwise evolution of gastric carcinogenesis and to test dietary chemopreventive agents. Development of multitargeted preventive and therapeutic strategies for gastric cancer is a major challenge for the future.

ABSTRACT A psychrotrophic, gram positive, non-spore forming bacterial strain was isolated from a soil sample taken from Parand area, Tehran-Iran. This bacterium was in short rods forming orange colonies on agar plates due to the formation of isoprenoid pigments. It was able to grow at temperatures ranging from 0 to 47 °C and the optimum temperature for growth was 37 °C. The growth pH was determined ranging from 5 to 12 and the optimum pH for growth was 7. The halotolerant strain was able to grow at NaCl concentrations ranging from 0 to 17%. The biochemical characteristics of the bacterium were assayed using API kit. The molecular identification of this strain was conducted using 16S rDNA sequencing. The gene coding for 16S rRNA was amplified by PCR using universal primers 27F and 1492R. The PCR product was a fragment of 1570 bp. This fragment was sequenced and used for similarity search using Blast suite at NCBI. The results were analyzed using Mega5 software to reveal the Phylogenetic relation of the isolate with other bacterial strains. Based on the biochemical and molecular analyses, this isolate was identified belonging to Exiguobacterium genus with most similarity with E. undae, E. antarcticum, and E. acetylicum.

ABSTRACT Cold-adapted enzymes produced by psychrotrophic organisms are interesting from both molecular and biotechnological viewpoints. The enzymes show superior catalytic activity than their mesophilic and thermophilic counterparts at room temperature.In this study, the production of cold-adapted amylolitic by Exiguobacterium sp. Sh3 was optimized and modeled. In the first step, single factor experiments using shake flask cultures were conducted for primary optimization. In the next step, the Plackett–Bur man design was used to identify significant factors affecting the amylolytic enzymes production. Starch concentration, tryptone concentration, and temperature were selected as significant factors for amylase and CaCl2 concentration,Tempreture and Time for pullulanase. in this step. Finally, the response surface methodology based on central composite design (CCD) was used for fur ther optimiza tion and modeling of the significant factors. The optimization efforts resulted in the maximum amylase production of 730 U/mL and for pullulanase production of 942 U/ml.

ABSTRACT The aim of this work was to study the effects of cultural parameters on Pullulanase production of Exiguobacterium sp. SH3. This bacterium produces an interesting cold-adapted Pullulanase with high catalytic activity at temperatures approaching freezing condition. To this aim, the combinatorial effects of seven cultural parameters including: time (h), temperature(c), pH, shaking speed (rpm), yeast extract (g/l), tryptone (g/l), starch (%) were analyzed at two levels using Plackett–Burman and Central composed design. The results indicated that the effects of 3 factors including temperature (25 and 40oC), yeast extract (1 and 3 g/l), and shaking speed (100 and 180 rpm) were statistically significant resulting in improved amylase productions. Temperature at lower level while yeast extract and shaking speed at higher levels were more suitable for Pullulanase production and secretion by this bacterium. The results revealed that cold condition is more suitable for Pullulanase production by this psychrotrophic bacterium. Yeast as a general growth-improving factor and shaking as an important factor for aerobic organisms at higher levels were effective. The newly psychrophilic PullulanaseSH3 seems to be suitable biocatalyst for practical use in liquefaction of starch at low temperature, detergent and textile industries. Biotechnology-2012 ISSN: 2155-952X JBTBM, an open access journal September 13-15, 2012 Volume 2 Issue 6 -347 3 rd World Congress on Biotechnology September 13-15, 2012 Hyderabad International Convention Centre, Hyderabad, India

ABSTRACT Cold-adapted enzymes, elaborated by psychrophiles and psychrotrophs, seem to have potential for current and future applications. In the current study, pullulanase production by the cold-adapted Exiguobacterium sp. SH3 was investigated. The Plackett–Burman design and the response surface methodology were applied to identify and optimize the significant variables affecting the pullulanase production of Exiguobacterium sp. SH3. The results showed that temperature, time, and CaCl2 concentration were significant variables while shaking, starch, yeast extract, tryptone, pH, MnCl2, MgCl2, and KH2PO4 were not significant. Using statistical analyses and optimizations, the pullulanase production was significantly elevated from 200 ± 18 to 950 ± 27 U/mL (4.75 times) as compared to non-optimized conditions. A pullulanase of about 70 kDa, designated as Pul-SH3, was purified 16.2-folds from the optimized culture, and identified to be an amylopullulanase. The Km and Vmax of the enzyme were 0.069 mg/mL and 967 U/mL, respectively. The optimum pH and temperature for maximum activity of Pul-SH3 were 7.5 and 30°C, respectively. As a cold-adapted enzyme, Pul-SH3 retained 23% of the maximum activity at 0°C. The biochemical characteristics and N-terminal amino acid sequence of Pul-SH3 suggest that the enzyme is a novel cold-adapted amylopullulanase with remarkably high specific activity at moderate ambient temperature.

People with haemophilia in Iran live with the disabling legacy of international economic sanctions against the country, which were lifted in 2016 (see also S. Shahabi et al. Nature 520, 157; 2015).

Iran has the highest number of people with haemophilia in the Middle East. Timely administration of the blood-clotting protein factor VIII, which is deficient in haemophilia, can prevent physical disability.

According to the annual global survey by the World Federation of Hemophilia and reports from the director of Iran’s Haemophilia Society, the mean per capita use of factor VIII in Iran was 0.5 international units (IU) after sanctions were imposed in 2006, down from 1.6 before. The drop was a result of a shortage of the protein and inflated prices during the sanctions era. It left about 1,000 people who have haemophilia with physical impairment as a result of bleeding into their joints, and some individuals died from uncontrolled bleeding (see go.nature.com/2jfj9ow).

The lifting of sanctions has made a big difference: the per capita use of factor VIII in Iran has now risen to 2.7 IU. We hope that the slow improvement in the country’s public-health services and pharmaceutical research can continue uninterrupted by political interference.