Publications by authors named "N Ashraf"

157 Publications

UCP3 (Uncoupling Protein 3) Insufficiency Exacerbates Left Ventricular Diastolic Dysfunction During Angiotensin II-Induced Hypertension.

J Am Heart Assoc 2021 Sep 17:e022556. Epub 2021 Sep 17.

Department of Physiology and Biophysics University of Mississippi Medical Center Jackson MS.

Background Left ventricular diastolic dysfunction, an early stage in the pathogenesis of heart failure with preserved ejection fraction, is exacerbated by joint exposure to hypertension and obesity; however, the molecular mechanisms involved remain uncertain. The mitochondrial UCP3 (uncoupling protein 3) is downregulated in the heart with obesity. Here, we used a rat model of UCP3 haploinsufficiency (ucp3) to test the hypothesis that decreased UCP3 promotes left ventricular diastolic dysfunction during hypertension. Methods and Results Ucp3 rats and ucp3 littermates fed a high-salt diet (HS; 2% NaCl) and treated with angiotensin II (190 ng/kg per min for 28 days) experienced a similar rise in blood pressure (158±4 versus 155±7 mm Hg). However, UCP3 insufficiency worsened diastolic dysfunction according to echocardiographic assessment of left ventricular filling pressures (E/e'; 18.8±1.0 versus 14.9±0.6; <0.05) and the isovolumic relaxation time (24.7±0.6 versus 21.3±0.5 ms; <0.05), as well as invasive monitoring of the diastolic time constant (Tau; 15.5±0.8 versus 12.7±0.2 ms; <0.05). Exercise tolerance on a treadmill also decreased for HS/angiotensin II-treated ucp3 rats. Histological and molecular analyses further revealed that UCP3 insufficiency accelerated left ventricular concentric remodeling, detrimental interstitial matrix remodeling, and fetal gene reprogramming during hypertension. Moreover, UCP3 insufficiency increased oxidative stress and led to greater impairment of protein kinase G signaling. Conclusions Our findings identified UCP3 insufficiency as a cause for increased incidence of left ventricular diastolic dysfunction during hypertension. The results add further support to the use of antioxidants targeting mitochondrial reactive oxygen species as an adjuvant therapy for preventing heart failure with preserved ejection fraction in individuals with obesity.
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http://dx.doi.org/10.1161/JAHA.121.022556DOI Listing
September 2021

Crocus transcription factors CstMYB1 and CstMYB1R2 modulate apocarotenoid metabolism by regulating carotenogenic genes.

Plant Mol Biol 2021 Sep 21;107(1-2):49-62. Epub 2021 Aug 21.

Plant Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Sanat Nagar, Srinagar, Jammu and Kashmir, 190005, India.

Key Message: Two MYB genes have been identified which regulate apocarotenoid metabolism in Crocus sativus. Apocarotenoids like crocin, picrocrocin and safranal are restricted to genus Crocus and are synthesized by oxidative cleavage of zeaxanthin followed by glycosylation reactions. In Crocus sativus, these apocarotenoids are synthesized in stigma part of the flower in developmentally regulated manner. Most of the genes of apocarotenoid pathway are known, however, the mechanism that regulates its tissue and stage specific biosynthesis remains elusive. MYB family was identified as the largest transcription factor family from Crocus transciptome which indicated its possible role in apocarotenoid regulation besides regulating other metabolic pathways. Towards this, we started with identification of 150 MYB genes from Crocus transcriptome databases. The phylogenetic analysis of Crocus MYB genes divided them into 27 clusters. Domain analysis resulted in identification of four groups of MYBs depending upon the number of R repeats present. Expression profiling indicated that 12 MYBs are upregulated in stigma out of which expression of four genes CstMYB1, CstMYB14, CstMYB16 and CstMYB1R2 correlated with crocin accumulation. Transient overexpression of two nuclear localized MYB genes (CstMYB1 and CstMYB1R2) in Crocus confirmed their role in regulating carotenoid metabolism. Yeast-one-hybrid confirmed that CstMYB1 binds to carotenoid cleavage dioxygenase 2 (CCD2) promoter while CstMYB1R2 binds to phytoene synthase (PSY) and CCD2 promoters. Overall, our study established that CstMYB1 and CstMYB1R2 regulate apocarotenoid biosynthesis by directly binding to promoters of pathway genes.
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http://dx.doi.org/10.1007/s11103-021-01180-6DOI Listing
September 2021

Surveillance of molecular markers of antimalarial drug resistance in Plasmodium falciparum and Plasmodium vivax in Federally Administered Tribal Area (FATA), Pakistan.

Rev Inst Med Trop Sao Paulo 2021 30;63:e59. Epub 2021 Jul 30.

The University of Haripur, Department of Microbiology, Haripur, Khyber Pakhtunkhwa, Pakistan.

This molecular epidemiological study was designed to determine the antimalarial drug resistance pattern, and the genetic diversity of malaria isolates collected from a war-altered Federally Administered Tribal Area (FATA), in Pakistan. Clinical isolates were collected from Bajaur, Mohmand, Khyber, Orakzai and Kurram agencies of FATA region between May 2017 and May 2018, and they underwent DNA extraction and amplification. The investigation of gene polymorphisms in drug resistance genes (dhfr, dhps, crt, and mdr1) of Plasmodium falciparum and Plasmodium vivax was carried out by pyrosequencing and Sanger sequencing, respectively. Out of 679 PCR-confirmed malaria samples, 523 (77%) were P. vivax, 121 (18%) P. falciparum, and 35 (5%) had mixed-species infections. All P. falciparum isolates had pfdhfr double mutants (C59R+S108N), while pfdhfr/pfdhps triple mutants (C59R+S108N+A437G) were detected in 11.5% of the samples. About 97.4% of P. falciparum isolates contained pfcrt K76T mutation, while pfmdr1 N86Y and Y184F mutations were present in 18.2% and 10.2% of the samples. P. vivax pvdhfr S58R mutation was present in 24.9% of isolates and the S117N mutation in 36.2%, while no mutation in the pvdhps gene was found. Pvmdr1 F1076L mutation was found in nearly all samples, as it was observed in 98.9% of isolates. No significant anti-folate and chloroquine resistance was observed in P. vivax; however, mutations associated with antifolate-resistance were found, and the chloroquine-resistant gene has been observed in 100% of P. falciparum isolates. Chloroquine and sulphadoxine-pyrimethamine resistance were found to be high in P. falciparum and low in P. vivax. Chloroquine could still be used for P. vivax infection but need to be tested in vivo, whereas a replacement of the artemisinin combination therapy for P. falciparum appears to be justified.
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http://dx.doi.org/10.1590/S1678-9946202163059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323834PMC
August 2021

Intraoperative Computed Tomography Scanner-Guided Craniovertebral Junction Surgery in a Patient with an Occipitalized C1.

J Neurosci Rural Pract 2021 Jul 7;12(3):603-607. Epub 2021 May 7.

Department of Neurosurgery, Allama Iqbal Medical College, Jinnah Hospital Lahore, Lahore, Pakistan.

Craniovertebral junction surgery is associated with unique difficulties. Type 2 odontoid fractures (Anderson and D Alonzo) have a great potential for nonunion and malunion. These fracture patients may require a circumferential decompression and fixation. The addition of intraoperative CT with neuronavigation greatly aids in craniovertebral junction surgery. We operated on a 59-year-old-male with a type 2 fracture with posterior subluxation of C1 anterior arch and a cranially displaced odontoid peg. First, a transoral odontoidectomy was performed followed by a craniocervical fixation. Occipital plates and C3-C4 lateral mass screws were used as C1 was discovered to be occipitalized intraoperatively and atlantoaxial facet joints could not be reduced as discovered by intraoperative CT resconstruction. Intraoperative CT scan was crucial to this circumferential decompression and fixation, allowed us to resect the odontoid peg safely and completely and to confirm adequate screw trajectory making this complex surgery easier for us and safer for the patient. The patient was discharged 4 months after admission with stable neurology. Intraoperative CT was fundamental to correct decision making.
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http://dx.doi.org/10.1055/s-0041-1730088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289552PMC
July 2021

Food habits of indian crested porcupine (Hystrix indica) (Kerr 1792), in district Bagh, Azad Jammu and Kashmir.

Braz J Biol 2021 14;82:e243063. Epub 2021 Jul 14.

Department of Zoology, University of Azad Jammu and Kashmir Muzaffarabad, AJ&K Pakistan.

The Indian Crested Porcupine (Hystrix indica) is classified as an agricultural pest species. It feeds on plants and crops; hence, it is responsible for massive financial losses worldwide. The current study was conducted to assess the diet composition of Indian Crested Porcupine in District Bagh, Azad Jammu and Kashmir (AJ&K). Thus, fecal samples were collected and examined from different sampling sites. Reference slides of the material collected from the study area were prepared for identification of dietary components in fecal pellets. A total of 80 fecal samples were collected and processed. Percent relative frequencies (P.R.F.) were calculated for each plant species recovered from pellets. Data revealed that Indian Crested Porcupine consumed 31 plant species in its diet, among them Zea mays (34.31±7.76) was the most frequently selected species followed by Rumex obtusifolius (15.32±2.57) and Melia azedarach (12.83±4.79). The study revealed that the greatest diversity of (n=20) plant species were consumed in summer season while minimum (n=13) species were used during winter. Among the parts of plants, stem was highly consumed in spring (57.2%) as compared to seed in fall (36.7%) while spikes and leaf were the least recovered parts from the fecal matter. The Berger-Parker diversity index showed highly diversified food (10.92) in the summer time of the year as compared to the autumn season (2.95). This study provides a baseline for the diet preference of this pest in the study area. Based on current findings, a detailed investigation on damage assessment, exploration, habitat use and management of Indian Crested Porcupine in AJ&K has been recommended.
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http://dx.doi.org/10.1590/1519-6984.243063DOI Listing
July 2021
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