Search results for: mitochondrial dysfunction

Authors: Emel Sonmezer, Hayri Baran Yosmaoglu

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The negative impact of chronic pain syndromes on sexual function has been reported in several studies; however, the influences of treatment strategies on sexual dysfunction have not been evaluated widely. The aim of this study was to determine the effects of pelvic floor exercise on sexual dysfunction in female patients with chronic low back pain. Forty-two patient with chronic low back pain were enrolled this study. Subjects were divided into two groups. Group 1 received conventional physiotherapy consist of heat therapy, ergonomic education, William flexion exercise during 6 weeks. Group 2 received pelvic floor exercises in addition to conventional physiotherapy. Female Sexual Function Index (FSFI) was used for the assessment of sexual function. Pain intensity was assessed with Visual Analogue Scale. Quality of life was assessed with World Health Organization Quality of Life Scale. All measurements were taken before and after treatment. In conventional physiotherapy group; there were significant improvement in pain intensity (p= 0,003), physical health (p=0,011), psychological health (p=0,042) subscales of quality of life scale, arousal (p=0,042), lubrication (p=0,028) and pain (p= 0,034) subscales of FSFI. In additional pelvic floor exercise group; there were significant improvement in pain intensity (p= 0,005), physical health (p=0,012) psychological health (p=0,039) subscales of quality of life scale, arousal (p=0,024), lubrication (p=0,011), orgasm (p=0,035) and pain (p= 0,015) subscales and total score (p=0,016) of FSFI. Total FSFI score (p=0,025) and orgasm (p=0,017) subscale of FSFI were significantly higher for the additional pelvic floor exercise group than the conventional physiotherapy group.The outcome of this study suggested that conventional physiotherapy may contribute to improve pain, quality of life and some parameters of the sexual function in patients with low back pain. Although additional pelvic floor exercise did not reveal more treatment effect in terms of quality of life and pain intensity, it caused significant improvement in sexual function. It is recommended that pelvic floor exercise should be added to treatment programs in order to manage sexual dysfunction more effectively in patients with chronic low back pain.

Keywords: physiotherapy, chronic pain, sexual dysfunction, pelvic floor

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Authors: Yogesh Rai, Saurabh Singh, Sanjay Pandey, Dhananjay K. Sah, B. G. Roy, B. S. Dwarakanath, Anant N. Bhatt

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One of the most common signatures of highly malignant gliomas is their capacity to metabolize more glucose to lactic acid than normal brain tissues, even under normoxic conditions (Warburg effect), indicating that aerobic glycolysis is constitutively upregulated through stable genetic or epigenetic changes. However, oxidative phosphorylation (OxPhos) is also required to maintain the mitochondrial membrane potential for tumor cell survival. In the process of tumorigenesis, tumor cells during fastest growth rate exhibit both high glycolytic and high OxPhos. Therefore, metabolically reprogrammed cancer cells with combination of both aerobic glycolysis and altered OxPhos develop a robust metabolic phenotype, which confers a selective growth advantage. In our study, we grew the high glycolytic BMG-1 (glioma) cells with continuous exposure of mitochondrial uncoupler 2, 4, dinitro phenol (DNP) for 10 passages to obtain a phenotype of high glycolysis with enhanced altered OxPhos. We found that OxPhos modified BMG (OPMBMG) cells has similar growth rate and cell cycle distribution but high mitochondrial mass and functional enzymatic activity than parental cells. In in-vitro studies, OPMBMG cells showed enhanced invasion, proliferation and migration properties. Moreover, it also showed enhanced angiogenesis in matrigel plug assay. Xenografted tumors from OPMBMG cells showed reduced latent period, faster growth rate and nearly five folds reduction in the tumor take in nude mice compared to BMG-1 cells, suggesting that robust metabolic phenotype facilitates tumor formation and growth. OPMBMG cells which were found radio-resistant, showed enhanced radio-sensitization by 2-DG as compared to the parental BMG-1 cells. This study suggests that metabolic reprogramming in cancer cells enhances the potential of migration, invasion and proliferation. It also strengthens the cancer cells to escape the death processes, conferring resistance to therapeutic modalities. Our data also suggest that combining metabolic inhibitors like 2-DG with conventional therapeutic modalities can sensitize such metabolically aggressive cancer cells more than the therapies alone.

Keywords: 2-DG, BMG, DNP, OPM-BMG

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Authors: Maryam Zahedifard, Fadhil Lafta Faraj, Maryam Hajrezaie, Nazia Abdul Majid, Mahmood Ameen Abdulla, Hapipah Mohd Ali

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In the current study, we prepared two new quinazoline schiff bases through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The chemical structures of both newly synthesized compounds (1 and 2) were confirmed by FT-IR and X-ray crystallography studies. The cytotoxic effect of compounds was investigated against MCF-7 human breast cancer cells. MTT results showed that (1) and (2) decreased the viability of MCF-7 cells in a time-dependent manner, exhibiting an IC50 value of 3.23 ± 0.28 µg/mL and 3.41 ± 0.34 µg/mL, respectively, after a 72-hours treatment period. In contrast, they did not show significant anti-proliferative effect towards MCF-10A normal breast cells and WRL-68 normal liver cells. We found a perturbation in mitochondrial membrane potential and increased cytochrome c release from the mitochondria to the cytosol, suggesting an activation of apoptosis by compounds, which was confirmed by activation of the initiator caspase-9 and the executioner caspases-3/7. (1) was also able to trigger extrinsic pathway via activation of caspase-8 and inhibition of NF-κB translocation. The acute toxicity test showed no toxicity effect of the compounds in rats. Our results showed that the selected synthesized compounds are highly potent to induce apoptosis in MCF-7 cells via either intrinsic or extrinsic mitochondrial pathway.

Keywords: Quinazoline Schiff base, apoptosis, MCF-7 human breast cancer cell line, caspase, NF-κB translocation

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Authors: V. R. Ahire, A. Kumar, B. N. Pandey, K. P. Mishra, G. R. Kulkarni

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Radiation therapy is an effective vital strategy used globally in the treatment of cervical cancer. However, radiation efficacy principally depends on the radiosensitivity of the tumor, and not all patient exhibit significant response to irradiation. A radiosensitive tumor is easier to cure than a radioresistant tumor which later advances to local recurrence and metastasis. Herbal polyphenols are gaining attention for exhibiting radiosensitization through various signaling. Current work focuses to study the radiosensitization effect of ellagic acid (EA), on HeLa cells. EA intermediated radiosensitization of HeLa cells was due to the induction γ-H2AX foci formation, G1 phase cell cycle arrest, and loss of reproductive potential, growth inhibition, drop in the mitochondrial membrane potential and protein expression studies that eventually induced apoptosis. Irradiation of HeLa in presence of EA (10 μM) to doses of 2 and 4 Gy γ-radiation produced marked tumor cytotoxicity. EA also demonstrated radio-protective effect on normal cell, NIH3T3 and aided recovery from the radiation damage. Our results advocate EA to be an effective adjuvant for improving cancer radiotherapy as it displays striking tumor cytotoxicity and reduced normal cell damage instigated by irradiation.

Keywords: apoptotic radiosensitivity, ellagic acid, mitochondrial potential, cell-cycle arrest

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Authors: Thaminda Liyanage, Chamila Shamika Kurukulasuriya

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Introduction: Morbid obesity has been successfully treated with bariatric surgery for over 60 years. Although operative procedures have improved and associated complications have reduced substantially, surgery still carries the risk of post-operative malabsorption, malnutrition and a range of gastrointestinal disorders. Overweight by itself can impair libido in both sexes and cause erectile dysfunction in males by inducing a state of hypogonadotropic hypogonadism, proportional to the degree of obesity. Impact of weight reduction on libido and sexual activity remains controversial, however it is broadly accepted that weight loss improves sexual drive. Zinc deficiency, subsequent to malabsorption, may lead to impaired testosterone synthesis in men while excessive and/or rapid weight loss in females may result in reversible amenorrhoea leading to sub-fertility. Methods: We describe a 37 year old male, 6 years post Roux-en-Y gastric bypass surgery, who presented with erectile dysfunction, loss of libido, worsening fatigue and generalized weakness for 4 months. He also complained of constipation and frequent muscle cramps but denied having headache, vomiting or visual disturbances. Patient had lost 38 kg of body weight post gastric bypass surgery over four years {135kg (BMI 42.6 kg/m2) to 97 kg (BMI 30.6 kg/m2)} and the weight had been stable for past two years. He had no recognised co-morbidities at the time of the surgery and noted marked improvement in general wellbeing, physical fitness and psychological confident post surgery, up until four months before presentation. Clinical examination revealed dry pale skin with normal body hair distribution, no thyroid nodules or goitre, normal size testicles and normal neurological examination with no visual field defects or diplopia. He had low serum testosterone, follicular stimulating hormone (FSH), luteinizing hormone (LH), T3, T4, thyroid stimulating hormone (TSH), insulin like growth factor 1 (IGF-1) and 24-hour urine cortisol levels. Serum cortisol demonstrated an appropriate rise to ACTH stimulation test but growth hormone (GH) failed increase on insulin tolerance test. Other biochemical and haematological studies were normal, except for low zinc and folate with minimally raised liver enzymes. MRI scan of the head confirmed a solid pituitary mass with no mass effect on optic chiasm. Results: In this patient clinical, biochemical and radiological findings were consistent with anterior pituitary dysfunction. However, there were no features of raised intracranial pressure or neurological compromise. He was commenced on appropriate home replacement therapy and referred for neurosurgical evaluation. Patient reported marked improvement in his symptoms, specially libido and erectile dysfunction, on subsequent follow up visits. Conclusion: Sexual dysfunction coupled with non specific constitutional symptoms has multiple aetiologies. Clinical symptoms out of proportion to nutritional deficiencies post bariatric surgery should be thoroughly investigated. Close long term follow up is crucial for overall success.

Keywords: obesity, bariatric surgery, erectile dysfunction, loss of libido

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Authors: Shalini Adiga, Shashikant Chetty, Jisha, Shobha Kamath

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Background: Moderate impairment of learning and memory has been observed in both type 1 and 2 diabetes mellitus in humans and experimental animals. A Change in glucose utilization and oxidative stress that occur in diabetes are considered the main reasons for cognitive dysfunction. Objective: Costus igneus (CI) which is known to possess hypoglycemic activity was evaluated in this study for its effect on learning and memory in normal and diabetic rats. Methods: Wistar rats were divided into control, CI-alcoholic extract treated normal (250 and 500mg/kg), diabetic control and CI-treated diabetic groups. CI treatment was continued for 4 weeks. For induction of diabetes, a single dose of streptozotocin was injected (30 mg/kg i.p). Entrance latency and time spent in the dark room during acquisition and at 24 and 48h after an aversive shock in a passive avoidance model was used as an index of learning and memory. Glutathione and malondialdehyde levels in brain and blood glucose were measured. Data was analysed using ANOVA. Results: During the three trials in exploration test, the diabetic control rats exhibited no significant change in entrance latency or in the total time spent in the dark compartment. During retention testing, the entrance latency of the diabetic treated groups was two times less at 24h and three times less at 48h after aversive stimulus as compared to diabetic rats. The normal drug-treated rats showed similar behaviour as the saline control. Treatment with CI significantly reduced the raised blood sugar and MDA levels of diabetic rats. Conclusion: Costus igneus prevented the cognitive dysfunction in diabetic rats which can be attributed to its antioxidant and antihyperglycemic activities.

Keywords: Costus igneous, diabetes, learning and memory, cognitive dysfunction

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Authors: Diana A. Pazmino, Lynne vanHerwerden, Colin A. Simpfendorfer, Claudia Junge, Stephen C. Donnellan, Mauricio Hoyos-Padilla, Clinton A. J. Duffy, Charlie Huveneers, Bronwyn Gillanders, Paul A. Butcher, Gregory E. Maes

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With just a handful of documented cases of hybridisation in cartilaginous fishes, shark hybridisation remains poorly investigated. Small amounts of admixture have been detected between Galapagos (Carcharhinus galapagensis) and dusky (Carcharhinus obscurus) sharks previously, generating a hypothesis of ongoing hybridisation. We sampled a large number of individuals from areas where both species co-occur (contact zones) across the Pacific Ocean and used both mitochondrial and nuclear-encoded SNPs to examine genetic admixture and introgression between the two species. Using empirical, analytical approaches and simulations, we first developed a set of 1,873 highly informative and reliable diagnostic SNPs for these two species to evaluate the degree of admixture between them. Overall, results indicate a high discriminatory power of nuclear SNPs (FST=0.47, p < 0.05) between the two species, unlike mitochondrial DNA (ΦST = 0.00 p > 0.05), which failed to differentiate between these species. We identified four hybrid individuals (~1%) and detected bi-directional introgression between C. galapagensis and C. obscurus in the Gulf of California along the eastern Pacific coast of the Americas. We emphasize the importance of including a combination of mtDNA and diagnostic nuclear markers to properly assess species identification, detect patterns of hybridisation, and better inform management and conservation of these sharks, especially given the morphological similarities within the genus Carcharhinus.

Keywords: elasmobranchs, single nucleotide polymorphisms, hybridisation, introgression, misidentification

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Authors: Mehak Nagpal, T. S. Sathyanarayan Rao

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Background: Sexual functioning is a neglected aspect of health in women with diabetes, though it contributes greatly towards quality of life and feeling of wellbeing. Also women with DM are at higher risk than men of developing sexual dysfunction and depression. Materials and Methods: Cross-sectional comparison study. Sample size: 100 previously diagnosed type 2DM patients attending Outpatient Diabetic Clinic at Medicine department JSS Hospital Mysore; aged 20-65 years and 60 normal healthy female subjects for Control group. Data was collected with ethical approval over a period of 2 years. Tools Used: 1) Hamilton Depression Rating Scale (HAMD – 17 item) 2) Female Sexual Functioning Index (FSFI) 3) Arizona Sexual Experience Scale (ASEX-F) for female-for screening. 4) The Appraisal of Diabetes Scale (ADS). Results: Statistically significant differences were observed in prevalence rate and severity of depression between diabetic group (45% vs 11% syndromal depression) and controls. Depression scores correlated significantly with glycaemic control, adherence to treatment, BMI and the cognitive appraisal of diabetes. There was significantly greater impairment in the sexual functioning of women with type 2 diabetes mellitus as compared to controls; both prevalence (62% vs 38.3%) and severity (p value < 0.01). Arousal (74.2% vs 53.3%), Desire (76.3% vs 50%) and Satisfaction (76.7% vs 63.7%) were most affected and 64.5% were affected in 2 or more domains. A negative illness appraisal on ADS correlated significantly with poor glycaemic control, higher rates of depression and also more severe female sexual dysfunction (p value < 0.05). Conclusion: Diabetes specific factors that correlated significantly with FSD in this study included the psychological appraisal of diabetes, duration of diabetes, presence of complications and BMI.

Keywords: depression, female sexual dysfunction, India, type 2 diabetes mellitus

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Authors: Asma Karim

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Fish taxonomy plays a fundamental role in the study of biodiversity. However, traditional methods of fish taxonomy rely on morphological features, which can lead to confusion due to great similarities between closely related species. To overcome this limitation, modern taxonomy employs DNA barcoding as a species identification method. This involves using a short standardized mitochondrial DNA region as a barcode, specifically a 658 base pair fragment near the 5′ ends of the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene, to exploit the diversity in this region for identification of species. To test the effectiveness and reliability of DNA barcoding, 25 fish specimens from nine different fish species found in various rivers of Pakistan were identified morphologically using a dichotomous key at the start of the study. Comprising nine freshwater fish species, including Mystus cavasius, Mystus bleekeri, Osteobrama cotio, Labeo rohita, Labeo culbasu, Labeo gonius, Cyprinus carpio, Catla catla and Cirrhinus mrigala from different rivers of Pakistan were used in the present study. DNA was extracted from one of the pectoral fins and a partial sequence of CO1 gene was amplified using the conventional PCR method. Analysis of the barcodes confirmed that genetically identified fishes were the same as those identified morphologically at the beginning of the study. The sequences were also analyzed for biodiversity and phylogenetic studies. Based on the results of the study, it can be concluded that DNA barcoding is an effective and reliable method for studying biodiversity and conducting phylogenetic analysis of different fish species in Pakistan.

Keywords: DNA barcoding, fresh water fishes, taxonomy, biodiversity, Pakistan

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Authors: Ahmad Rasyadan Arshad, A. Rahman A. Jamal, N. Mohamed Ibrahim, Nor Azian Abdul Murad

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Introduction: Parkinson’s disease (PD) is a complex and asymptomatic disease where patients are usually diagnosed at late stage where about 70% of the dopaminergic neurons are lost. Therefore, identification of molecular biomarkers is crucial for early diagnosis of PD. MicroRNA (miRNA) is a short nucleotide non-coding small RNA which regulates the gene expression in post-translational process. The involvement of these miRNAs in neurodegenerative diseases includes maintenance of neuronal development, necrosis, mitochondrial dysfunction and oxidative stress. Thus, miRNA could be a potential biomarkers for diagnosis of PD. Objective: This study aim to identify the miRNA involved in Late Onset PD (LOPD) and Early Onset PD (EOPD) compared to the controls. Methods: This is a case-control study involved PD patients in the Chancellor Tunku Muhriz Hospital at the UKM Medical Centre. miRNA samples were extracted using miRNeasy serum/plasma kit from Qiagen. The quality of miRNA extracted was determined using Agilent RNA 6000 Nano kit in the Bioanalyzer. miRNA expression was performed using GeneChip miRNA 4.0 chip from Affymetrix. Microarray was performed in EOPD (n= 7), LOPD (n=9) and healthy control (n=11). Expression Console and Transcriptomic Analyses Console were used to analyze the microarray data. Result: miR-129-5p was significantly downregulated in EOPD compared to LOPD with -4.2 fold change (p = <0.050. miR-301a-3p was upregulated in EOPD compared to healthy control (fold = 10.3, p = <0.05). In LOPD versus healthy control, miR-486-3p (fold = 15.28, p = <0.05), miR-29c-3p (fold = 12.21, p = <0.05) and miR-301a-3p (fold = 10.01, p =< 0.05) were upregulated. Conclusion: Several miRNA have been identified to be differentially expressed in EOPD compared to LOPD and PD versus control. These miRNAs could serve as the potential biomarkers for early diagnosis of PD. However, these miRNAs need to be validated in a larger sample size.

Keywords: early onset PD, late onset PD, microRNA (miRNA), microarray

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Authors: Sandisiwe Mangali, Graeme Bradley

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Genome is complete set of the organism's hereditary information encoded as either deoxyribonucleic acid or ribonucleic acid in most viruses. The three different types of genomes are nuclear, mitochondrial and the plastid genome and their sequences which are uncovered by genome sequencing are known as an archive for all genetic information and enable researchers to understand the composition of a genome, regulation of gene expression and also provide information on how the whole genome works. These sequences enable researchers to explore the population structure, genetic variations, and recent demographic events in threatened species. Particularly, genome sequencing refers to a process of figuring out the exact arrangement of the basic nucleotide bases of a genome and the process through which all the afore-mentioned genomes are sequenced is referred to as whole or complete genome sequencing. Gelidium pristoides is South African endemic Rhodophyta species which has been harvested in the Eastern Cape since the 1950s for its high economic value which is one motivation for its sequencing. Its endemism further motivates its sequencing for conservation biology as endemic species are more vulnerable to anthropogenic activities endangering a species. As sequencing, mapping and annotating the Gelidium pristoides genome is the aim of this study. To accomplish this aim, the genomic DNA was extracted and quantified using the Nucleospin Plank Kit, Qubit 2.0 and Nanodrop. Thereafter, the Ion Plus Fragment Library was used for preparation of a 600bp library which was then sequenced through the Ion S5 sequencing platform for two runs. The produced reads were then quality-controlled and assembled through the SPAdes assembler with default parameters and the genome assembly was quality assessed through the QUAST software. From this assembly, the plastid and the mitochondrial genomes were then sampled out using Gelidiales organellar genomes as search queries and ordered according to them using the Geneious software. The Qubit and the Nanodrop instruments revealed an A260/A280 and A230/A260 values of 1.81 and 1.52 respectively. A total of 30792074 reads were obtained and produced a total of 94140 contigs with resulted into a sequence length of 217.06 Mbp with N50 value of 3072 bp and GC content of 41.72%. A total length of 179281bp and 25734 bp was obtained for plastid and mitochondrial respectively. Genomic data allows a clear understanding of the genomic constituent of an organism and is valuable as foundation information for studies of individual genes and resolving the evolutionary relationships between organisms including Rhodophytes and other seaweeds.

Keywords: Gelidium pristoides, genome, genome sequencing and assembly, Ion S5 sequencing platform

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Authors: Zeina Nasr, Bashar Merheb

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The honey bee is a social insect that had driven the human interest much more than any other organism. Beekeeping practices dated the appearance of Man on earth and now it provides a hobby or a secondary work that contributes to the family revenue and requires a little time engagement and money investment. Honey production is not the only contribution of honey bees to the economy, since honey bees play an important role in the pollination. Bee keeping in Lebanon is an important part of the agricultural economy. However, a growing concern about bees is spreading globally, due to an accelerated decline of bees colonies. This raises the alert to preserve and protect local bee strains against uncontrolled introduction of foreign strains and invasive parasitic species. Mitochondrial DNA (mtDNA) markers are commonly used in studying genetic variation in the Apis mellifera species. The DraI-COI-COII test is based on the analysis of the intergenic region between the two genes COI and COII. The different honey bee strains differ in the presence or absence of the p sequence and the number of Q sequences present. A. m. syriaca belonging to the lineage Z, is the native honey bee subspecies in Lebanon, Syria, Jordan, and Palestine. A. m. syriaca is known for its high defensiveness, even though it has many important advantages. However, commercial breeder strains, such as the Italian (A. m. ligustica), and Carniolan (A. m. carnica) strains, have been introduced by beekeepers and regularly used for honey production. This raises worries about the disappearance of the local subspecies. It is obvious that identifying A. m. syriaca colonies and protecting them against uncontrolled mating with other bee strains is a crucial step to protect and improve the original local strain. This study aims to reveal the existing sub-species of honey bee in Akkar – Lebanon and to assess the influence of introgression on the hybridization of the local strain. This will help to identify areas of pure A.m. syriaca population over this district to be considered in choosing syriaca reserves. We collected samples of bees from different regions of Akkar district in order to perform mtDNA analysis. We determined the restriction fragments length of the intergenic region COI-COII, using the restriction enzyme DraI. The results showed both the C and the Z lineages. Four restriction patterns were identified among the restriction maps of the studied samples. The most abundant mitochondrial lineage is the Z lineage constituting about 60% of the identified samples. Al-Dreib region reported the lowest introgression with foreign mtDNA of 21% making it the most suitable area for a genetic reserve of syriaca in Akkar based on its lowest introgression and suitable environment in addition to the attitude of local beekeepers to conserve the local strain. Finally, this study is the first step in constructing conservation programs for the preservation of the local strain and should be generalized to the whole Lebanese population, consistent with the effort done in neighboring countries.

Keywords: Akkar Lebanon, Apis millefera syriaca, DraI-COI-COII test, mitochondrial DNA

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Authors: Shohra Qaderi

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Introduction: Tetanus is a severe infection characterized by the spasm of skeletal muscles that often progresses toward respiratory failure. Acute Renal failure (ARF) is an important complication associated Tetanus infection, occurring in 15%-39% of cases. Presentation of cases: A previous healthy 14-year-old boy was admitted to the Tetanus ward of a hospital in Kabul, presenting with severe muscle spasms. On day four of admission, he started having cola-colored urine with decreased urine output. Due to lack of peritoneal dialysis, he went under hemodialysis in view of rapidly raising in blood urea (from baseline 32 mg/dl to 150 mg/dl) and creatinine from (baseline 0.9 mg/dl to 6.2g/dl). Despite all efforts, he had a sudden cardiac arrest and passed away on day 6 of admission. Discussion: ARF is a complication of tetanus, reported to be mild and non-oliguric. Suggested pathological mechanisms include autonomic dysfunction and rhabdomyolysis, owing to uncontrolled muscle spasms. Autonomic dysfunction, most evident in the first two weeks of infection. Conclusion: The prevalence and mortality of tetanus is high in Afghanistan. Physicians and pediatricians need to be aware of this complication of tetanus so as to take appropriate preventive measures and recognize and manage it early.

Keywords: afghanistan, acute renal failure, child, mortality

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Authors: G. Dadashova, A. Bakhshaliyev

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Aim: Determine gender differences in the etiology and clinical outcomes, as well as in the remodeling of the left ventricle (LV) in patients with chronic heart failure (CHF), suffering from arterial hypertension (AH) and coronary heart disease (CHD). Material and methods: The study included 112 patients of both sexes; aged 45 to 60 years with postinfarction cardiosclerosis had functional class (FC) heart failure II-IV of NYHA which were examined on the basis of Azerbaijan Scientific Research Institute of Cardiology. The patients were divided into 2 groups: 1st c. 60 males, mean age 54,8 ± 3,3 years, and 2nd gr 52 women, mean age 55,8 ± 3,1 years. To assess cardiac hemodynamic all patients underwent echocardiography (B-M-modes) using ‘Vivid 3’. Thus on the basis of indicators such as the index of the relative thickness of the left ventricle wall and the index of left ventricular mass (LVMI) was identified the architectonic model of the left ventricle. Results: According to our research leading cause of heart failure in women is 50.5% of cases of hypertension, ischemic heart disease 23.7% (with 79.5% of the cases developed in patients with chronic heart failure who did not have a history of myocardial infarction). While in men is the undisputed leader of CHD, forming 78.3% of CHF (80.3% in men with CHF occurred after myocardial infarction). According to our research in women more often than men CHF develops a type of diastolic dysfunction (DD, and left ventricular ejection fraction remained unchanged. Since DD occurs in men at 65,8% vs. 76,4% of women when p < 0,05. In the group of women was more common prognostic neblagopryatnye remodeling - eccentric hypertrophy of the left ventricle: 68% vs. 54.5% among men (p < 0,05), concentric left ventricular hypertrophy: 21% in women vs 19,1% (p > 0,05 ). Conclusions: Patients with heart failure are a number of gender-specific: the prevalence of hypertension in women, and coronary heart disease in men. While in women with heart failure often recorded diastolic dysfunction and characterized by the development of prognostically unfavorable remodeling types: eccentric and concentric LV hypertrophy.

Keywords: chronic heart failure, arterial hypertension, remodeling, diastolic dysfunction, men, women, ischemic heart disease

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Authors: Rostyslav Horbay, Nick Korolis, Vahid Anvari, Rostyslav Stoika

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Introduction: Giant cancer cells (GCC) are common in all types of cancer, especially after poor therapy. Some specific features of such cells include ~10-fold enlargement, drug resistance, and the ability to propagate similar daughter cells. We used murine NK/Ly lymphoma, an aggressive and fast growing lymphoma model that has already shown drastic changes in GCC comparing to parental cells (chromatin condensation, nuclear fragmentation, tighter OXPHOS/cellular respiration coupling, multidrug resistance). Materials and methods: In this study, we compared morpho-functional changes of GCC that predominantly show either a cytostatic or a cytotoxic effect after treatment with drugs. We studied the effect of a combined cytostatic/cytotoxic drug treatment to determine the correlation of drug efficiency and GCC formation. Doses of G1/S-specific drug paclitaxel/PTX (G2/M-specific, 50 mg/mouse), vinblastine/VBL (50 mg/mouse), and DNA-targeting agents doxorubicin/DOX (125 ng/mouse) and cisplatin/CP (225 ng/mouse) on C57 black mice. Several tests were chosen to estimate morphological and physiological state (propidium iodide, Rhodamine-123, DAPI, JC-1, Janus Green, Giemsa staining and other), which included cell integrity, nuclear fragmentation and chromatin condensation, mitochondrial activity, and others. A single and double factor ANOVA analysis were performed to determine correlation between the criteria of applied drugs and cytomorphological changes. Results: In all cases of treatment, several morphological changes were observed (intracellular vacuolization, membrane blebbing, and interconnected mitochondrial network). A lower gain in ascites (49.97% comparing to control group) and longest lifespan (22+9 days) after tumor injection was obtained with single VBL and single DOX injections. Such ascites contained the highest number of GCC (83.7%+9.2%), lowest cell count number (72.7+31.0 mln/ml), and a strong correlation coefficient between increased mitochondrial activity and percentage of giant NK/Ly cells. A high number of viable GCC (82.1+9.2%) was observed compared to the parental forms (15.4+11.9%) indicating that GCC are more drug resistant than the parental cells. All this indicates that the giant cell formation and its ability to obtain drug resistance is an expanding field in cancer research.

Keywords: ANOVA, cisplatin, doxorubicin, drug resistance, giant cancer cells, NK/Ly lymphoma, paclitaxel, vinblastine

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Authors: Foluke E. Sola-Ojo, Ibraheem A. Abubakar, Semiu F. Bello, Isiaka H. Fatima, Sule Bisola, Adesina M. Olusegun, Adeniyi C. Adeola

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The domesticated pigeon, Columba livia domestica, has many valuable characteristics, including high nutritional value and fast growth rate. There is a lack of information on its genetic diversity in Nigeria; thus, the genetic variability in mitochondrial cytochrome oxidase subunit I (COI) sequences of 150 domestic pigeons from four different locations was examined. Three haplotypes (HT) were identified in Nigerian populations; the most common haplotype, HT1, was shared with wild and domestic pigeons from Europe, America, and Asia, while HT2 and HT3 were unique to Nigeria. The overall haplotype diversity was 0.052± 0.025, and nucleotide diversity was 0.026± 0.068 across the four investigated populations. The phylogenetic tree showed significant clustering and genetic relationship of Nigerian domestic pigeons with other global pigeons. The median-joining network showed a star-like pattern suggesting population expansion. AMOVA results indicated that genetic variations in Nigerian pigeons mainly occurred within populations (99.93%), while the Neutrality tests results suggested that the Nigerian domestic pigeons’ population experienced recent expansion. This study showed a low genetic diversity and population differentiation among Nigerian domestic pigeons consistent with a relatively conservative COI sequence with few polymorphic sites. Furthermore, the COI gene could serve as a candidate molecular marker to investigate the genetic diversity and origin of pigeon species. The current data is insufficient for further conclusions; therefore, more research evidence from multiple molecular markers is required.

Keywords: Nigeria pigeon, COI, genetic diversity, genetic variation, conservation

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Authors: A. Benedetto, P. Wong, N. Papouchis, L. W. Samstag

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Bowen’s concept of self-differentiation describes a healthy balance of autonomy and intimacy in close relationships, and it has been widely researched in the context of family dynamics. The current study aimed to clarify the impact of family dysfunction on self-differentiation by specifically examining conflict between parents, and by including young adults, an underexamined age group in this domain (N = 300; ages 18 to 30). It also identified a protective factor for offspring from conflictual homes. The 300 young adults (recruited online through Mechanical Turk) completed the Differentiation of Self Inventory (DSI), the Children’s Perception of Interparental Conflict Scale (CPIC), the Parental Bonding Instrument (PBI), and the Symptom Checklist-90-Revised (SCL-90-R). Analyses revealed that interparental conflict significantly impairs self-differentiation among young adult offspring. Specifically, exposure to parental conflict showed a negative impact on young adults’ sense of self, emotional reactivity, and interpersonal cutoff in the context of close relationships. Parental conflict was also related to increased psychological distress among offspring. Surprisingly, the study found that parental divorce does not impair self-differentiation in offspring, demonstrating the distinctly harmful impact of conflict. These results clarify a unique type of family dysfunction that impairs self-differentiation, specifically in distinguishing it from parental divorce; it examines young adults, a critical age group not previously examined in this domain; and it identifies a moderating protective factor (a strong parent-child bond) for offspring exposed to conflict. Overall, results suggest the need for modifications in parental behavior in order to protect offspring at risk of lasting emotional and interpersonal damage.

Keywords: divorce, family dysfunction, parental conflict, parent-child bond, relationships, self-differentiation, young adults

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Authors: Parinaz Tavakoli Zaniani, Dimitrios Balomenos

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Mitochondrial reactive oxygen species (mROS) play a crucial role in macrophage pro-inflammatory activation, although a detailed understanding of the mechanism and kinetics by which mROS drive signaling molecules is still lacking. In general, it is thought that NF-κB activation drives mROS and general ROS production. Here, We performed a detailed kinetic analysis of mROS production during macrophage activation. We found early mROS generation after LPS (lipopolysaccharide) stimulation. Remarkably as early as 5 minutes, mROS signaling promoted initial NF-κB, MAPK activation and pro-inflammatory cytokine production, as established through inhibition or quenching of mROS. On the contrary, NF-κB inhibition had no effect on mROS production. Our findings point to a mechanism by which mROS increase TRAF-6 ubiquitination and, thus NF-κB activity. mROS inhibition reduced LPS-induced lethality in an in vivo septic shock model by controlling pro-inflammatory cytokine production. Overall, our research provides novel insights into the role of mROS as a primary messenger in the pathway of macrophage and as a regulator of inflammatory responses. We found that early mROS production promotes initial NF-κB, and MAPK activation by regulating TRAF-6 ubiquitination and that mROS inhibition can reduce LPS-induced inflammatory cytokines and lethality in a septic shock model. These findings might lead to novel immunotherapeutic strategies targeting early mROS production and control of extreme inflammation in the context of sepsis and other inflammatory diseases.

Keywords: mitochondria, reactive oxygen species, nuclear factor κB, lipopolysaccharide, macrophages

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Authors: Vidhula Ahire, Amit Kumar, K. P. Mishra, Gauri Kulkarni

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Herbal polyphenols have gained significance because of their increasing promise in prevention and treatment of cancer. Therefore, development of a dietary compound as an effective radiosensitizer and a radioprotector is highly warranted for cervical cancer patients undergoing therapy. This study describes the cytotoxic effects of the flavonoid, ellagic acid (EA) when administered either alone or in combination with gamma radiation on cervical cancer HeLa cells in vitro. Apoptotic index and proliferation were measured by using trypan blue assay. Reproductive cell death was analyzed by clonogenic assay. Propidium iodide staining for flowcytometry was performed to analyze cell cycle modulation. Nuclear and mitochondrial changes were studied with specific dyes. DNA repair kinetics was analyzed by immunofluorescence assay. Evaluation and comparison of EA effects were performed with other clinically used breast cancer drugs. When tumor cells were exposed to 2 and 4 Gy of irradiation in presence of EA (10 μM), it yielded a synergistic cytotoxic effect on cervical cancer cells whereas in NIH3T3 cells it reversed the injury caused by irradiation and abetted in the regaining of normal healthy cells. At 24h ~25foci/cell was observed and 2.6 fold decrease in the mitochondrial membrane potential. Up to 40% cell were arrested in the G1 phase and 20-36% cells exhibited apoptosis. Our results demonstrate the role of increased apoptosis and cell cycle modulation in the mechanism of EA mediated radiosensitization of cervical cancer cells and thus advocating EA as an adjuvant for preclinical trials in cancer chemo- radiotherapy.

Keywords: cervical cancer, ellagic acid, sensitization, radiation therapy

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Authors: Noraziah Nordin, Najihah Mohd Hashim, Nazia Abdul Majid, Mashitoh Abdul Rahman, Hamed Karimian, Hapipah Mohd Ali

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Enicosanthellum pulchrum belongs to family Annonaceae is also known as family of 'mempisang' in Malaysia. Liriodenine was isolated by prep-HPLC method. This method was first technique used for the isolation of this compound. The structure of the liriodenine was elucidated by 1D and 2D spectroscopy techniques. Liriodenine was tested on ovarian cancer cells line (CAOV-3) for MTT, AO/PI and cytotoxicity 3 assays. The MTT assay was performed to determine the cytotoxicity effect of lirodenine on CAOV-3 cells. The morphological changes on CAOV-3 cells were observed by AO/PI assay for the early and late stage of apoptosis, as well as necrosis. Meanwhile, the measurement of cell loss, nuclear morphology, DNA content, cell membrane permeability, mitochondrial membrane potential changes and cytochrome c release from mitochondria were detected through cytotoxicity 3 assay. The IC50 results showed liriodenine inhibits the growth of CAOV-3 cells after 24 h of treatment at 10.25 ± 1.06 µg/mL. After 48 and 72 h of treatments, the IC50 values were decreased to 7.65 ± 0:07 and 6.35 ± 1.62 µg/mL, respectively. The morphology changes can be seen on CAOV-3 with a production of cell membrane blebbing, cromatin condensation and apoptotic bodies with increasing time of treatment from 24 to 72 h. Evaluation of cytotoxicity 3 on CAOV-3 cells after treated with liriodenine, resulting loss of mitochondrial membrane potential and release of cytochrome c from mitochondria. The results demonstrated the capability of liriodenine as a promising anticancer agent, particularly on human ovarian cancer.

Keywords: Enicosanthellum pulchrum, ovarian cancer, apoptosis, cytotoxicity

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Authors: Hasan Afarnegan, Ali Shahraki, Jafar Shahraki

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Paraquat is widely used as a strong nitrogen-based herbicide for controlling of weeds in agriculture. This poison is extremely toxic for humans which induces several – organ failure by accumulation in cells and many instances of death occurred due to its poisoning. Paraquat metabolized primarily in the liver. The purpose of this study was to assess the effects of aquatic extract of levisticum officinale on oxidative status and biochemical factors in hepatocytes exposed to paraquat. Our results determined that hepatocytes destruction induced by paraquat is mediated by reactive oxygen species (ROS) production, lipid peroxidation and decrease of mitochondrial membrane potential were significantly (P<0.05) prevented by aquatic extract of Levisicum officinale (100, 200 and 300 µg/ml). These effects of paraquat also prevented via antioxidants and ROS scavengers (α-tocopherol, DMSO, manitol), mitochondrial permeability transition (MPT) pore sealing compound (carnitine).MPT pore sealing compound inhibited the hepatotoxicity, indicating that paraquat induced cell death via mithochondrial pathway. Pretreatment of hepatocytes with aquatic extracts of Levisticum officinale, antioxidants and ROS scavengers also blocked hepatic cell death caused by paraquat, suggesting that oxidative stress may be directly induced decline of mithochondrial membrane potential. In conclusion, paraquat hepatotoxicity can be attributed to oxidative stress and continued by mithochondrial membrane potential disruption. Levisticum officinale aquatic extract, presumably due to its strong antoxidant properties, could protect the destructive effects of paraquat on rat hepatocytes.

Keywords: hepatocyte protection, levisticum officinale, oxidative stress, paraquat

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Authors: Styliani Kotrotsiou, Evagelia Kotrotsiou, Fani Mokia, Theodosis Paralikas, Konstantinos Tsaras

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Objective: The objective of this study was the investigation of the mental health of patients undergoing chronic or transient hemodialysis at Artificial Kidney Unit, as well as its relationship to the demographic characteristic of patients. Material and Method: The study took place in Larisa during the month of December in 2016 and the sample was composed of 60 patients undergoing in chronic or transient hemodialysis at Artificial Kidney Unit of the University General Hospital of Larisa. For the investigation of the physical and mental health of patients who participated in the study, the tool measurement << General Health Questionnaire- 28 >> (GHQ-28) was used. The questionnaires were administered with the interview method during the hemodialysis. This survey is designed for the existence or not of a mental disorder. It examines four factors (physical symptoms, anxiety, social dysfunction and depression). Results: The hemodialysis patients gave the following scores: -to the physical symptoms, women showed a higher average value than men (1,16 ± 1,26 against 0,49 ± 0,93), -at the anxiety scale, it seems that women are superior to men (1,68 ± 1,20 against 0,90 ± 1,22), -at the social dysfunction scale, the elderly patients ( > 65 years old) were presented a with higher average (2,59), and -at the depression scale, patients with a higher average value were those who lived in non-urban areas. The appearance of mental disorder, in relation to patient characteristics, did not show significant statistical correlation. The sex, the age and the place of residence affect more the assessment of mental health, while education did not seem to have any significant effect on the other. Conclusions: The hemodialysis process can significantly affect the patient’s Quality of Life and it can bring adverse changes in lifestyle, affecting the physical, social and psychological state of the individual. For that reason, hemodialysis should be aimed not only at extending life but in upgrading the Quality of Life.

Keywords: hemodialysis, chronic kidney disease, depression, social dysfunction, physical condition

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Authors: Adar Pelah, Avraham Adelman, Amanda Balash, Jake Mitchell, Mattan J. Pelah, Viswadeep Sarangi, Xin Chen Cai, Zadok Storkey, Gregg B. Fields, Ximena Levy, Ali A. Danesh

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Introduction: Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 infection (PASC), or Long COVID, while primarily a respiratory disorder, can also include dizziness, lasting weeks to months in individuals who had previously tested positive for COVID-19. This study utilized gait analysis to assess the potential vestibular effects of PASC on the presentation of gait anomalies. Materials and Methods: The study included 11 participants who tested positive for COVID-19, a mean of 2.8 months prior to gait testing (PP=11), and 8 control participants who did not test positive for COVID-19 (NP=8). Participants walked 7.5m at three self-selected speeds: ‘slow,’ ‘normal,’ and ‘fast.’ Mean walking speeds were determined for each speed and overall range from four laps on an instrumented walkway using video capture. Results: A Z-test at 0.05 significance was used for speed range, ‘normal’ and ‘fast’ at the lower tail, and for ‘slow’ at the higher tail. Average speeds (m/s) were: ‘slow’ (PP=0.709, NP=0.678), ‘normal’ (PP=1.141, NP=1.170), ‘fast’ (PP=1.529, NP=1.821), average range (PP=0.846, NP=1.143). Significant speed decreases between PP and NP were observed in ‘fast’ (-17.43%) and average range (-29.86%), while changes in ‘slow’ (+2.44%) and ‘normal’ (-4.39%) speeds were not significant. Conclusions: Long COVID is a recognized disability (Americans with Disabilities Act), and although it presents variably, dizziness, vertigo, and tinnitus are not uncommon in COVID-19 infection. These results suggest that potential inner-ear damage may persist and manifest in gait changes even after recovery from acute illness. Further research with a larger sample size may indicate the need for providers to consider PASC when diagnosing patients with vestibular dysfunction.

Keywords: gait analysis, long-COVID, vestibular dysfunction, walking speed

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Authors: Dian Ariyawati, Romi Sukoco, Sinung Agung Joko

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Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a form of orthostatic intolerance caused by autonomic dysfunction. POTS predominantly occurs in young women. Regular exercise has proven to improve the organ system functions, including autonomous systems. The aim of this research was to determine the correlation between exercise frequency and POTS in young women. Method: 510 young women (16-23 years of age) were screened. They were obtained by interview and physical examination. The diagnosis of POTS was performed with Active Stand Test (AST) and heart rate measurement using a pulsemeter. There were 29 young women who suffered from POTS. The exercise frequency was obtained by interview. Data was statistically analyzed using Spearman Correlation test. Result: The subjects’, who tested positive for POTS didn’t perform regular exercise. The Spearman correlation test showed there was a moderate negative correlation between exercise frequency and POTS in young women (r = -0.487, p < 0.00). Conclusion: There is a moderate reverse correlation between exercise frequency and POTS in young women. Further studies are suggested to develop an exercise program for young who suffered from POTS.

Keywords: POTS, autonomic dysfunction, exercise frequency, young woman

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Authors: Silvia Di Giacomo, Marcello Locatelli, Simone Carradori, Francesco Cacciagrano, Chiara Toniolo, Gabriela Mazzanti, Luisa Mannina, Stefania Cesa, Antonella Di Sotto

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Hyperglycemia represents the main pathogenic factor in the development of diabetes complications and has been found associated with mitochondrial dysfunction and oxidative stress, which in turn increase cell dysfunction. Therefore, counteract oxidative species appears to be a suitable strategy for preventing the hyperglycemia-induce cell damage and support the pharmacotherapy of diabetes and metabolic diseases. Antidiabetic potential of many food sources has been linked to the presence of polyphenolic metabolites, particularly flavonoids such as quercetin and its glycosylated form rutin. In line with this evidence, in the present study, we assayed the potential anti-hyperglycemic activity of an ethyl acetate extract from the peel of Punica granatum L. var. Dente di Cavallo (PGE), a fruit well known to traditional medicine for the beneficial properties of its edible juice. The effect of the extract on the glucidic metabolism has been evaluated by assessing its ability to inhibit α-amylase and α-glucosidase, two digestive enzymes responsible for the hydrolysis of dietary carbohydrates: their inhibition can delay the carbohydrate digestion and reduce glucose absorption, thus representing an important strategy for the management of hyperglycemia. Also, the PGE ability to block the release of advanced glycated end-products (AGEs), whose accumulation is known to be responsible for diabetic vascular complications, was studied. The iron-reducing and chelating activities, which are the primary mechanisms by which AGE inhibitors stop their metal-catalyzed formation, were evaluated as possible antioxidant mechanisms. At last, the phenolic content of PGE was characterized by chromatographic and spectrophotometric methods. Our results displayed the ability of PGE to inhibit α-amylase enzyme with a similar potency to the positive control: the IC₅₀ values were 52.2 (CL 27.7 - 101.2) µg/ml and 35.6 (CL 22.8 - 55.5) µg/ml for acarbose and PGE, respectively. PGE also inhibited the α-glucosidase enzyme with about a 25 higher potency than the positive controls of acarbose and quercetin. Furthermore, the extract exhibited ferrous and ferric ion chelating ability, with a maximum effect of 82.1% and 80.6% at a concentration of 250 µg/ml respectively, and reducing properties, reaching the maximum effect of 80.5% at a concentration of 10 µg/ml. At last, PGE was found able to inhibit the AGE production (maximum inhibition of 82.2% at the concentration of 1000 µg/ml), although with lower potency with respect to the positive control rutin. The phytochemical analysis of PGE displayed the presence of high levels of total polyphenols, tannins, and flavonoids, among which ellagic acid, gallic acid and catechin were identified. Altogether these data highlight the ability of PGE to control the carbohydrate metabolism at different levels, both by inhibiting the metabolic enzymes and by affecting the AGE formation likely by chelating mechanisms. It is also noteworthy that peel from pomegranate, although being a waste of juice production, can be reviewed as a nutraceutical source. In conclusion, present results suggest the possible role of PGE as a remedy for preventing hyperglycemia complications and encourage further in vivo studies.

Keywords: anti-hyperglycemic activity, antioxidant properties, nutraceuticals, polyphenols, pomegranate

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Authors: Amna Imtiaz

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Aims: To correlate serum ferritin with left ventricular function in beta thalassemia major patients with increased transfusion dependence and to find out whether echocardiography can be used to assess pre clinical cardiac disease in these patients. Methods: The cross sectional study was conducted at Department of Pathology, Shaheed Zulfiqar Ali Bhutto Medical University, Pakistan Institute of Medical Sciences, Islamabad. 60 patients of beta thalassemia major with increased transfusion dependence were enrolled in this study. Serum ferritin levels of all patients were measured by using indirect enzyme linked immunosorbent assay (ELISA). Echocardiography was performed on all patients by a consultant cardiologist by linking conventional echocardiography with tissue Doppler imaging. Ejection fraction and E/A ratio were measured in all patients to assess left ventricular systolic and diastolic function. Results: On the basis of serum ferritin level, patients were divided into three groups. Group I consisted of patients having serum ferritin level equal to or less than 2500 ng/ml. A total of 25 patients were placed in this group. Group II included patients having serum ferritin level between 2500 to 5000 ng/ml. A total of 22 patients were placed in this group. Group III included patients having serum ferritin level more than 5000 ng/ml. This group consisted of 13 patients. All patients having serum ferritin below 2500ng/ml had normal systolic function, and only 16% of the patients in this group had diastolic dysfunction as reflected by abnormal E/A ratio. In group II, 27% of the patients had systolic dysfunction reflected by subnormal ejection fraction while 40% of the patients had diastolic dysfunction. In group III, 62% of the patients had abnormal systolic and diastolic function. Pearson correlation was used to find a correlation between serum ferritin and left ventricular function. A strong negative correlation was found which is reflected by a p value of less than 0.05 which is significant. Chi square test is used to correlate serum ferritin with E/A ratio. P value came out to be less than 0.05 which is significant.

Keywords: beta thalassemia major, left ventricular function, serum ferritin, transfusion dependence

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Authors: Hossam M. Abdallah, Ali M. El-Halawany, Gamal A. Mohamed, Khalid Z. Alshali, Zainy M. Banjar, Hany A. El-Bassossy

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Hypertension and vascular dysfunction are major components and complications of many diseases like metabolic syndrome. In addition, vascular dysfunction is considered the initial step in diabetic atherosclerosis, the main etiology for mortality and a great percent of morbidity in diabetic patients. In spite of the significant developments in antidiabetic therapy, diabetic complications, particularly seen in long-term diabetes, continue to be seriously deleterious. Herbal drugs are prescribed widely in treatment of different aliment because of their effectiveness, fewer side effects and relatively low cost. Nine plants belong to five different families grown in Kingdom of Saudi Arabia were evaluated for their effect on exaggerated vasoconstriction and impaired relaxation in aortae isolated from metabolic syndrome rats. The aerial parts of Onopordum ambiguum Fresen. (OA), Astragalus abyssinicus Steud. (AA), Pulicaria Arabica Cass. (PA), Echinops sheilae Kit Tan (ES), Aizoon canariense L. (AC), Cleome viscosa L. (CV), Chrozophora oblongifolia (Delile) A.Juss. ex Spreng (CO), Centaurea pseudosinaica Mouterde (CP) and Tephrosia nubica Baker (TN) were dried and extracted with methanol. The effect of thirty minute incubation with the total extracts (10-330 µg/ml) or their fractions on the exaggerated vasoconstriction response to phenylephrine (10nM to 10microM) and impaired vasodilation to acetylcholine (10-330 µg /ml) of aortae isolated from metabolic syndrome animals was studied. Incubating aortae isolated from metabolic syndrome animals with total methanol extract of OA, AA, PA, AC, CV, and TN at concentrations (10-330 microgram/ml) in the organ bath led to concentration dependent alleviation of exaggerated vasoconstriction response to phenylephrine without having beneficial effect on impaired vasodilation to acetylcholine. In conclusion, addition of OA, AA, PA, AC, CV and TN to the standard therapies may provide superior means to alleviate the associated vascular complications.

Keywords: vascular dysfunction, exaggerated vasoconstriction, metabolic syndrome, Saudi plants

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Authors: Prajna Paramita Naik, Sujit Kumar Bhutia

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Background: Regardless of the development multimodal treatment strategies, oral squamous cell carcinoma (OSCC) is often associated with a high rate of recurrence, metastasis and chemo- and radio- resistance. The present study inspected the relevance of CD44, ABCB1 and ADAM17 expression as a putative stem cell compartment in oral squamous cell carcinoma (OSCC) and deciphered the role of autophagy in regulating the expression of aforementioned proteins, stemness and chemoresistance. Methods: A retrospective analysis of CD44, ABCB1 and ADAM17 expression with respect to the various clinicopathological factors of sixty OSCC patients were determined via immunohistochemistry. The correlation among CD44, ABCB1 and ADAM17 expression was established. Sphere formation assay, flow cytometry and fluorescence microscopy were conducted to elucidate the stemness and chemoresistance nature of established cisplatin-resistant oral cancer cells (FaDu). The pattern of expression of CD44, ABCB1 and ADAM17 in parental (FaDu-P) and resistant FaDu cells (FaDu-CDDP-R) were investigated through fluorescence microscopy. Western blot analysis of autophagy marker proteins was performed to compare the status of autophagy in parental and resistant FaDu cell. To investigate the role of autophagy in chemoresistance and stemness, sphere formation assay, immunofluorescence and Western blot analysis was performed post transfection with siATG14 and the level of expression of autophagic proteins, mitochondrial protein and stemness-associated proteins were analyzed. The statistical analysis was performed by GraphPad Prism 4.0 software. p-value was defined as follows: not significant (n.s.): p > 0.05;*: p ≤ 0.05; **: p ≤ 0.01; ***: p ≤ 0.001; ****: p ≤ 0.0001 were considered statistically significant. Results: In OSCC, high CD44, ABCB1 and ADAM17 expression were significantly correlated with higher tumor grades and poor differentiation. However, the expression of these proteins was not related to the age and sex of OSCC patients. Moreover, the expression of CD44, ABCB1 and ADAM17 were positively correlated with each other. In vitro and OSCC tissue double labeling experiment data showed that CD44+ cells were highly associated with ABCB1 and ADAM17 expression. Further, FaDu-CDDP-R cells showed higher sphere forming capacity along with increased fraction of the CD44+ population and β-catenin expression FaDu-CDDP-R cells also showed accelerated expression of CD44, ABCB1 and ADAM17. A comparatively higher autophagic flux was observed in FaDu-CDDP-R against FaDu-P cells. The expression of mitochondrial proteins was noticeably reduced in resistant cells as compared to parental cells indicating the occurrence of autophagy-mediated mitochondrial degradation in oral cancer. Moreover, inhibition of autophagy was coupled with the decreased formation of orospheres suggesting autophagy-mediated stemness in oral cancer. Blockade of autophagy was also found to induce the restoration of mitochondrial proteins in FaDu-CDDP-R cells indicating the involvement of mitophagy in chemoresistance. Furthermore, a reduced expression of CD44, ABCB1 and ADAM17 was also observed in ATG14 deficient cells FaDu-P and FaDu-CDDP-R cells. Conclusion: The CD44+ ⁄ABCB1+ ⁄ADAM17+ expression in OSCC might be associated with chemoresistance and a putative CSC compartment. Further, the present study highlights the contribution of mitophagy in chemoresistance and confirms the potential involvement of autophagic regulation in acquisition of stem-like characteristics in OSCC.

Keywords: ABCB1, ADAM17, autophagy, CD44, chemoresistance, mitophagy, OSCC, stemness

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Authors: Shahzad Bhatti, M. Aslamkhan, Sana Abbas, Marcella Attimonelli, Hikmet Hakan Aydin, Erica Martinha Silva de Souza,

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Despite being situated at the crossroad of Asia, Pakistan has gained crucial importance because of its pivotal role in subsequent migratory events. To highlight the genetic footprints and to contribute an enigmatic picture of the relative population expansion pattern among four major Pashtun tribes in Khyber Pakhtunkhwa viz., Bangash, Khattak, Mahsuds and Orakzai, the complete mitochondrial control region of 100 Pashtun were analyzed. All Pashtun tribes studied here revealed high genetic diversity; that was comparable to the other Central Asian, Southeast Asian and European populations. The configuration of genetic variation and heterogeneity further unveiled through Multidimensional Scaling, Principal Component Analysis, and phylogenetic analysis. The results revealed that the Pashtun is a composite mosaic of West Eurasian ancestry of numerous geographic origin. They received substantial gene flow during different invasions and have a high element of the Western provenance. The most common haplogroups reported in this study are: South Asian haplogroup M (28%) and R (8%); whereas, West Asians haplogroups are present, albeit in high frequencies (67%) and widespread over all; HV (15%), U (17%), H (9%), J (8%), K (8%), W (4%), N (3%) and T (3%). Herein we linked the unexplored genetic connection between Ashkenazi Jews and Pashtun. The presence of specific haplotypes J1b (4%) and K1a1b1a (5%) point to a genetic connection of Jewish conglomeration with Khattak tribe. This was a result of an ancient genetic influx in the early Neolithic period that led to the formation of a diverse genetic substratum in present day Pashtun.

Keywords: mtDNA haplogroups, control region, Pakistan, KPK, ethnicity

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Authors: Dong-Gyu Leem, Ji-Sun Shin, Sang Yoon Choi, Kyung-Tae Lee

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In this study, we focused on the anti-proliferative effects of panaxydol, a C17 polyacetylenic compound derived from Panax ginseng roots, against various human cancer cells. We treated with panaxydol to various cancer cells and panaxydol treatment was found to significantly inhibit the proliferation of human lung cancer cells (A549) and human pancreatic cancer cells (AsPC-1 and MIA PaCa-2), of which AsPC-1 cells were most sensitive to its treatment. DNA flow cytometric analysis indicated that panaxydol blocked cell cycle progression at the G1 phase in A549 cells, which accompanied by a parallel reduction of protein expression of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D1 and cyclin E. CDK inhibitors (CDKIs), such as p21CIP1/WAF1 and p27KIP1, were gradually upregulated after panaxydol treatment at the protein levels. Furthermore, panaxydol induced the activation of p53 in A549 cells. In addition, panaxydol also induced apoptosis of AsPC-1 and MIA PaCa-2 cells, as shown by accumulation of subG1 and apoptotic cell populations. Panaxydol triggered the activation of caspase-3, -8, -9 and the cleavage of poly (ADP-ribose) polymerase (PARP). Reduction of mitochondrial transmembrane potential by panaxydol was determined by staining with dihexyloxacarbocyanine iodide. Furthermore, panaxydol suppressed the levels of anti-apoptotic proteins, XIAP and Bcl-2, and increased the levels of proapoptotic proteins, Bax and Bad. In addition, panaxydol inhibited the activation of Akt and extracellular signal-regulated kinase (ERK) and activated the p38 mitogen-activated protein kinase kinase (MAPK). Our results suggest that panaxydol is an anti-tumor compound that causes p53-mediated cell cycle arrest and apoptosis via mitochondrial apoptotic pathway in various cancer cells.

Keywords: apoptosis, cancer, G1 arrest, panaxydol

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