Iranian Journal of Basic Medical Sciences
Volume:22 Issue: 1, Jan 2019

Polycystic ovary syndrome (PCOS) is an endocrinopathy in women, which, unlike its impact on fertility and health of women, there is no clear understanding about the causal mechanisms of this pathogenesis. The aim of this review paper is to investigate the pathophysiological pathways affecting the PCOS etiology, based on functions of gonadotropins– and steroid hormones–related genes. Due to different hormonal and metabolic signs of this complex disorder, different hypotheses are mentioned about etiology of this syndrome. Because of the heterogeneity of the reasons given for this syndrome and the spread of the effective genes in its pathophysiology, most of genes affected by sex-related hormonal imbalances are examined for discriminative diagnosis. For this purpose, published articles and reviews dealing with genetic evaluation of PCOS in women in peer-reviewed journals in PubMed and Google Scholar databases were included in this review. In previous studies, it has been well demonstrated that PCOS in some individuals have a genetic origin. Pathophysiological functions of genes are primarily responsible for the synthesis of proteins that have role in PCOS before hyperandrogenism including GnRHR, FSHβ, FSHR, LHCGR, CYP19A1, HSD17B, AR and SHBG, and their effects in PCOS of human have been confirmed. Hormonal imbalances are the first reason mentioned in PCOS etiology, and usually characterized with menstrual irregularities in PCOS women. Hyperandrogenism and gonadotropin secretion disorders are shown in PCOS condition, which are related to steroidogenesis pathways and hypothalamic–pituitary–ovarian axis disturbances, respectively

Diazinon (DZ) is an organophosphate pesticide that induces oxidative damage in different organs. The aim of this study was to compare the effectiveness of nanomicelles containing curcuminoids (NCUR) and natural curcumin (CUR) in attenuating the oxidative damage induced by DZ in male rats. After a single intraperitoneal (IP) injection of DZ (100 mg/kg), the rats were administered either CUR or NCUR (25 and 60 mg/kg, IP). Biomarkers of cell damage including, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), creatinine (Cr), urea, lactate dehydrogenase (LDH), creatine kinase-MB isoenzyme (CK-MB) and troponin I, were quantified in the serum. Lipid peroxidation (LPO) and glutathione (GSH) content in the liver, kidney, and heart tissues were determined. DZ administration increased the serum levels of ALT, AST, ALP, Cr, urea, LDH, CK-MB, and troponin I; however, the levels significantly (P<0.001) decreased in the CUR- and NCUR-treated groups compared to those in the DZ group. NCUR significantly decreased LPO (P<0.05) and increased GSH (P<0.05) in the heart, kidney, and liver tissues at all doses (especially, at 60 mg/kg) compared with CUR Our findings suggest that NCUR treatment counters DZ-induced oxidative tissue damage to a greater extent than CUR

Leishmaniasis is one of the main health problems in developing countries, caused by intracellular protozoan parasites of the Leishmania genus. Although research has been successful in discovering vaccines and anti-parasitic drugs like antimony compounds, their side effects like high toxicity, prolonged regeneration, etc., have raised the replacement importance of natural products with antioxidant and antibacterial properties. It can be said that an appropriate alternative to this is the ozonated olive oil. Ozone by introducing O2 in involved tissues and bloodstream could degrade parasite amastigotes and lead to cleared leishmaniasis infections. So, the present study aimed to evaluate the effect of ozonated olive oil in Iranian leishmaniasis patients compared to glucantime, a choice drug for the treatment of Leishmaniasis. Thirty patients with confirmed leishmaniasis lesions were included and divided into two groups, 15 cases as control and 15 cases as test with lesions of 30–50 mm2 in diameter. The control group received glucantime intralesionally and the test group ozonated olive oil plus glucantime, 2 times daily. The mean of lesion size was (50.94±33.20) before and (15±14.34) after treatment in control (P<0.00) and (50.88±31.74) before and (9.93±14.18) after treatment in the test group (P<0.00). Moreover, the mean course of therapy was 10.4(±1.84) weeks and 8.93(±2.15) weeks in control and test groups, respectively (P=0.636). Significant differences were reported in lesion size after treatment between the two groups (P<0.00). Data suggested ozonated olive oil can have synergistic effects with glucantime in the treatment of cutaneous leishmaniasis

To reveal the detailed mechanism underlying the functions of salidroside on the inflammation of intestinal epithelial cells during IBD. Quantitative real-time PCR was employed to assess the expression of IL-6, IL-10, and α-defensins 5 and 6. ELISA assay was performed to measure the secretion of IL-6 and IL-10. MTT assay was used to determine the cell viability and proliferation. Western blot was used to assess the phosphorylation of NF-kB, Erk1/2, JNK, P38, JAK2, and STAT3. Salidroside impaired the proliferation of intestinal epithelial cells at high concentrations (P< 0.05) and down-regulated interleukin-6 (IL-6) production induced by LPS (P<0.05). Western blot results showed that salidroside repressed the phosphorylation of NF-kB, Erk1/2, JNK, P38, JAK2 and STAT3 (P<0.05) and attenuated the activation of NF-κB, MAPK, and STAT3 pathways. Moreover, the expressions of α-defensin 5 and 6 were rescued by salidroside after LPS or SAC triggering (P<0.05). In summary, salidroside suppressed the expression of IL-6 and elevated the expression of defensins in LPS-activated intestinal epithelial cells through NF-κB/MAPK and STAT3 pathways. The mechanism revealed here may be potentially useful for the treatment of IBD with salidroside

Resistance to carbapenems is the principal reason for the continuing utilization of colistin as a last resort choice for treating the infections resulted from multidrug carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates. The assessment of antimicrobial resistance pattern, the prevalence of carbapenem-resistance determinants, and molecular epidemiology of colistin-resistant isolates among CRPA strains were the aims of the present research. The current cross-sectional research was conducted on 269 CRPA isolates collected from various clinical samples from 2013 to 2016. After performing identification tests, disk diffusion as well as MIC methods were used for testing sensitivity to the antibiotics. Modified Hodge Test (MHT) was utilized to produce carbapenemase. PCR technique identified beta-lactamase classes A, B, and D genes. In total, from 269 CRPA, five isolates (1.3%) were resistant to colistin. It was found that blaNDM-1, blaIMP-1, blaVIM-2, and blaOXA-10 genes were present in 40%, 40%, 20%, and 100% of colistin-resistant isolates, respectively. DLST type 25-11 is a significant cluster of colistin-resistant P. aeruginosa isolates. The appearance of colistin-resistant isolates in CRPA carrying blaNDM-1 with multiple carbapenem-resistant genes shows the great problem in the treatment of P. aeruginosa infections

There is increasing evidence for the importance of gender in different diseases; however, the role of gender in response to treatments is still unknown. Therefore, this study investigated the impact of gender on the protective effects of celecoxib in ischemia reperfusion (IR)-induced acute kidney injury. In this experimental study, rats were randomly divided into 6 groups (n=6): IR, sham and celecoxib groups of males and females. In IR groups, after orally receiving saline for 5 days, renal pedicles were clamped for 55 min and then kidneys were reperfused for 24 hr. In the sham groups, clamping of renal pedicles was not performed. In the celecoxib groups, 30 mg/kg celecoxib was given orally for 5 days before induction of ischemia. Plasma was collected to determine creatinine (Cr) and blood urea nitrogen (BUN). Kidney tissue samples were also stored for examining the histopathology and measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities. IR caused significant increases in plasma Cr (P<0.05), BUN (P<0.05) and renal histopathological damages in both genders. Also, induction of IR resulted in significant increase of MDA levels (P<0.05) and decrease of SOD activities (P<0.05) in the kidney in both genders. Celecoxib administration prevented the IR-induced functional, histopathological and oxidative changes in both genders by similar degrees. This study suggested that in similar pathological conditions, celecoxib improves renal function and histopathological damages and attenuates oxidative stress in both genders by the same degrees. These protective effects of celecoxib on IR-induced kidney injury are gender-independent

Phytochemicals such as polyphenols, alkaloids, and terpenoids, protect against the development of early stages and complications of diabetes mellitus according to various reports. The aim of this study was to measure the anti-dyslipidemic and anti-diabetic effects of Citral on high-fat-diet (HFD) and streptozotocin (STZ) induced diabetic dyslipidemic rats and to see also its effect on carbohydrate metabolic regulatory enzymes in the liver. Rats were kept on a high-fat diet for 2 weeks, then diabetes was induced by a single dose of STZ (35 mg/kg/BW, intraperitoneally), Citral was administered orally at a dose of 45 mg/kg/BW for 28 days to diabetic rats. Blood glucose, plasma insulin, and lipid profile in blood were studied. Antioxidant activities were assayed in the liver, pancreas, and adipose tissues. Carbohydrate metabolic enzymes of the liver were also studied in diabetic dyslipidemic rats. The results of this study confirmed that administration of Citral significantly (P<0.05) decreased the blood glucose level and increased plasma insulin in diabetic rats. Citral also improved oxidative markers along with anti-oxidative enzymes of the liver, adipose tissue, and pancreas in the HFD/STZ group. Citral also regulated the activity of the glucose-metabolic enzymes in the liver. The results of the present study were compared to Glibenclamide, which is a standard oral drug for lowering the blood sugar. Results may show that Citral possesses anti-dyslipidemic activity as well as anti-diabetic activity and also regulates the enzyme activity of glycolytic and gluconeogenic processes in the liver

Pseudomonas aeruginosa infections such as keratitis are considered among the major health problems worldwide due to the complexity of pathogenesis and antibiotic resistance crisis, thus, finding new effective approaches for prevention and treatment of the infections seem to be still vital. In this report, we aimed to investigate the therapeutic effects of topical administration of the antibodies against type a and b-flagellin (FLA and FLB) in Pseudomonas keratitis model of infection in mice. Scratched corneas of mice were treated with approximately 107 CFUs/eye of PAK and/or PAO1 strains of P. aeruginosa. Specific IgG to FLA, FLB or divalent flagellin were topically applied to the infected corneas for 20 min, 24, and 36 hr post-infection. The bacterial burden and myeloperoxidase activity (as a marker for polymorphonuclears (PMNs) infiltration) were determined in the corneas. The biological activity of the anti-FLA and FLB IgG was evaluated in vitro by opsonophagocytosis test. Compared to other treated corneas, divalent anti-flagellin IgG treatment showed a significant decrease in the bacterial CFUs and myeloperoxidase activity in the infected corneas (P<0.05). Results of opsonophagocytosis revealed that the specific antibodies raised against FLA and FLB had more potent opsonic killing activity on their homologous strains as compared with control group (P<0.05). It appears that in P. aeruginosa keratitis, topical administration of the combined antibodies likely via decreasing the bacterial load, and PMNs infiltration as well as increasing opsonophagocytosis could lead to dramatic improvement of the infected corneas.

Recent evidence has shown underlying roles of gut dysbiosis and metabolic endotoxemia in obesity and its complications. Despite the large number of experimental and clinical researches performed on gut microbiota and obesity, no bibliometrics’ study has been conducted so far. We aimed to assess the trend of global scientific publications in the field of gut microbiota and obesity. The bibliometrics’ data from January 2000 to April 2017 were retrieved based on Scopus database. The analysis of the publication year, main source, citation, subject area, co-authorship network, and geographical distribution were carried out, accordingly. The data were analyzed using the Scopus analysis tools, SPSS version 15 and Visualizing Scientific Landscapes (VOS) viewer version 1.6.5. Out of 4384 documents that were identified, the United States published the highest number (28.2%), followed by China and United Kingdom. The number of publications showed an increasing trend over the years of which the most productive year was 2016. The leading subject area was medicine. Most of published scientific documents were original articles and the top source was “PLoS One”. The documents were cited totally 153576 times with average citations per article as 35.03, and h-index of 159. Top author in the co-authorship network assessment was “Wang J.” from China. This study could provide practical sources to researchers to find highly cited studies. Moreover, the study could pave the way for researchers to be engaged in studies which potentially lead to more publication in the field

The novel 1,5-diaryl-1,4-pentadien-3-one derivatives were studied for analgesic, anti-inflammatory and anticancer potential to establish their role in pain, inflammatory disorders and cancer. Two 1,5- diaryl-1,4-pentadien-3-one derivatives: (1E,4E)- 5-(4-fluoro phenyl)-1-(4-methoxyphenyl)- 2-methylpenta-1,4-dien-3-one (A2K2A17) and (1E,4E)-5-(4-nitrophenyl)-1-(4-nitrophenyl)-2-ethylhexa-1,4-dien-3-one (A11K3A11) were synthesized and characterized via 1H NMR and 13C NMR techniques. Molecular docking, anti-inflammatory, analgesic and anticancer activities were performed using Auto Doc Vina, carrageenan mediated paw edema and formalin induced chronic inflammation, acetic acid induced writhings and hotplate assay and brine-shrimp lethality assay. A2K2A17 and A11K3A11 showed high computational affinities (binding energy > -9.0 Kcal/mol) against COX-1, kappa receptor and braf kinase domain. A2K2A17 and A11K3A11 exhibited moderate docking affinities (binding energy > -8.0 Kcal/mol) against COX-2, human capsaicin receptor, tumor necrosis factor, lipoxygenase, colony stimulating factor, delta receptor, cyclin dependent protein kinase-2, mitogen activated kinase, mu receptor and kit kinase domain. A2K2A17 and A11K3A11 possess low docking affinities (binding energy > -7.0 Kcal/mol) against purinoceptor, platelets-derived growth Factor-1 and vascular-endothelial growth factor. In analgesic activity, A2K2A17 (1-30 mg/kg) and A11K3A11 (1-10 mg/kg) decreased acetic acid induced writhes and prolonged the latency time (P<0.01, P The in silico, in vitro and in vivo studies on A2K2A17 and A11K3A11 reports their computational binding affinities against targets as well as the analgesic, anti-inflammatory and the anticancer effects

The purpose of this study was to evaluate variations in yields, volatile composition and biological activities of essential oils (EOs) obtained from the aerial parts of Zhumeria majdae collected from five localities of the south of Iran. The EOs were analyzed using gas chromatography and gas chromatography-mass spectrometry techniques. The antioxidant activity of the EOs was tested using DPPH and β-carotene/linoleic acid assays. In vitro cytotoxicity was tested against two cancer cell lines (A375 and MCF7) using MTT assay. The oils yield varied from 6.3% (S2) to 10.2% (V/W) (S4). All of five investigated EOs samples presented three major compounds: linalool (24.4-34.6%), camphor (26.1-34.7%) and trans-linalool oxide (7.6-28.6%). Although the main constituents were common, their percentages were different. Among samples, S1 had a better antioxidant activity in both DPPH and β-carotene/linoleic acid methods (IC50= 8.01 and 11.77 mg/ml, respectively). In vitro cytotoxicity against two cancer cell lines of human melanoma cell line (A375) and breast cancer cell line (MCF7), showed a moderate cytotoxicity of S3 against A375 cells with IC50 value of 624 μg/ml. Tangezagh (S4) plant materials revealed the highest level of oil yield as the region is recommended for collecting the plant samples.Taken together, despite the weak antioxidant and moderate cytotoxic activities of tested EOs, this study suggested a proper potential for possible use of the EOs of Z. majdae for pharmaceutical and perfume industries

This study was aimed to evaluate whether single nucleotide polymorphisms (SNPs) of TLR4 and common living habits of prostate hyperplasia (BPH) patients would affect the subjects’ risk and prognosis. We totally recruited 501 BPH patients and 964 healthy controls. The patients’ international prostate symptom score (IPSS) and quality of life assessment (QoL) were designated as the prognostic indexes for BPH patients. Altogether 7 SNPs within TLR4 were selected, and the interactions among SNPs and living habits were explained with multi-factor dimensionality reduction (MDR) modeling. The mutant alleles of rs10983755 (G>A) and rs1927907 (G>A) tended to put on risk of BPH, yet the wide alleles of rs4986791 (C>T) and rs115336889 (G>C) were associated with incremental susceptibility to BPH (P<0.05). The rs10983755 (GA) and rs1927907 (GA) were suggested as the marker of non-aggressive BPH, whereas rs4986791 (TT) could symbolize aggressive BPH (P<0.05). The homozygotes of rs4986791 (TT) and rs115336889 (CC) could improve the IPSS change, and rs115336889 (CC) was also correlated with more obviously ameliorated Qol change (P<0.05). Finally, MDR modeling suggested that rs4986791 (TT) and rs115336889 (GG) shaped the genotyping combination featured by the lowest risk of BPH when smoking or drinking history was also evaluated. The SNPs situated within TLR4 were potent candidates for predicting risk and prognosis of BPH patients, and their interactions within environmental parameters also helped to develop effective strategies for preventing and treating BPH

Histone deacetylase inhibitory and cytotoxic activities of 18 naturally occuring terpenoids (ferutinin, stylosin, tschimgine and guaiol), coumarins (umbelliprenin, farnesiferone B, conferone, feselol, ligupersin A, conferdione, conferoside) and sulfur-containing derivatives (latisulfies A-E, persicasulphides A and C) from the roots of three species of Ferula (Ferula latisecta, Ferula ovina and Ferula flabelliloba) were evaluated. The cytotoxic activity of compounds was evaluated against human cancer cell lines (HeLa, HCT116, A2780 and A549) by AlamarBlue® assay using vorinostat as the positive control. On the other hand, we aimed to evaluate their inhibitory activities against pan-HDAC. The methanolic extract of the roots of F. flabelliloba was subjected to silica gel column chromatography. Further purification by preparative thin-layer chromatography (PTLC) and semipreparative RP-HPLC yielded twelve known compounds (1-12). This is the first report on the isolation of guaiol (1), persicasulphide C (3) and conferoside (10) from the roots of F. flabelliloba. Six compounds including persicasulfide A, conferone, feselol, latisufide C, conferoside and ferutinin showed cytotoxic activity with IC50 values in the range of 11.61-49.40 μM against cancer cells and pan-HDAC inhibitory activity with IC50 values in the range of 1.06-35.27 μM. Results indicated that persicasulfide A (2), conferone (6) and feselol (7) showed moderate cytotoxicity with IC50 values in the range of 11.76-39.24 μM against cancer cells and potent pan-HDAC inhibitory activity with IC50 values in the range of 1.06-10.73 μM. Conferone was more active than others with a higher potency for HDAC inhibition (1.06- 1.17 μM)

Hydrogen sulfide (H2S) attenuates ischemia-reperfusion injury (IRI) in different organs. However, its mechanism of action in renal IRI remains unclear. The present study investigated the hypothesis that H2S attenuates renal IRI via the induction of heat shock proteins (HSPs). Adult Wistar rats were subjected to unilateral renal ischemia for 45 min followed by reperfusion for 6 hr. One group of rats underwent I/R without treatment, one group was administered 150 μmol/l sodium hydrosulfide (NaHS) prior to I/R, one group was injected with 100 mg/kg quercetin (an HSP inhibitor) intraperitoneally prior to I/R, and another group received quercetin prior to I/R and treatment with NaHS following I/R. Two other groups underwent a sham operation and one of them received 150 μmol/l NaHS following the sham operation whereas the other received no treatment. Renal function and histological changes were compared and relevant indices of oxidative stress, apoptosis, and inflammation were examined. IRI increased serum creatinine and blood urea nitrogen concentrations, promoted lipid peroxidation by elevating malondialdehyde levels, suppressed superoxide dismutase activity, stimulated inflammation by inducing NF-kB, IL-2, and TLR-4 expression, and increased renal apoptosis. Levels of HSP70, heme-oxygenase-1 (HO-1) and HSP 27 were increased following IRI and reversed following H2S treatment. H2S attenuated changes observed in pathology, lipid peroxidation, inflammation, and apoptosis following IRI. The administration of quercetin reversed all protective effects of H2S. The present study indicated that H2S protected renal tissue against IRI induced lipid peroxidation, inflammation, and apoptosis, which may be attributed to the upregulation of HSP 70, HO-1, and HSP 27

Acinetobacter pittii has become an emerging opportunistic noscomial pathogen worldwide with multi-drug resistance. In the present study, an A. pittii strain was isolated from bronchoalveolar lavage fluid sample harboring both OXA-58 and NDM-1carbapenemase producing genes. The mechanisms of carbapenem resistance of the A. pittii strain was investigated. Carbapenemase producing genes were examined by PCR and DNA sequencing. S1-PFGE was used to localize carbapenemase encoding genes. Filter mating and electrotransformation were used to investigate the transferability of such carbapenemase encoding genes between different strains. Genetic surroundings of blaOXA-58 and blaNDM-1 genes were detected as well. The A. pittii strain, carrying both OXA-58 and NDM-1 carbapenemase encoding genes, was resistant to all β-lactam antibiotics, while suscepitible to ciprofloxacin, levofloxacin, tobramycin, cotrimoxazole and tigecycline. Southern blot hybridization for the blaOXA-58 and blaNDM-1 gene indicated that the two genes locate in the same plasmid with molecular weight of 310.1-336.5kb. BlaOXA-58 was located in an ISAba3-blaOXA-58-ISAba3-like structure, and the blaNDM-1 gene cluster was embedded in an ISAba125-aphA6- blaNDM-1-bleMBL-ΔtrpF-dsbC-cutA structure sequentially. In the present study, it is first reported an A. pittii clincal strain in China, co-harboring OXA-58 and NDM-1 carbapenemase producing genes residing on a same plasmid. In hospital and community settings, it is of great significance and urgence to increase the surveillance of these kinds of organisms