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1.
J Org Chem ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32425042

RESUMO

First total synthesis of cell surface phospholipomannan anchor [ß-Manp-(1→2)-ß-Manp]n-(1→2)-ß-Manp-(1→2)-α-Manp-1→P-(O→6)-α-Manp-(1→2)-Inositol-1-P-(O→1)-phytocer- amide of Candida albicans is reported. The target PLM anchor poses synthetic challenges such as unusual kinetically controlled (1→2)-ß-oligomannan domain, anomeric phosphodiester, and unique phytoceramide lipid tail linked to the glycan through a phosphate group. The synthesis of PLM anchor was accomplished using a convergent block synthetic approach using three main appropriately protected building blocks; (1→2)-ß-tetramann repeats, pseudodisaccharide, phytoceramide-1-H-phosphonate. The most challenging (1→2)-ß-tetramann domain was synthesized in one-pot by using pre-activation method. The phytoceramide-1-H-phosphonate was synthesized through an enantioselective A3 three-component coupling reaction. Finally, the phytoceramide-1-H-phosphonate moiety was coupled with pseudodisaccharide followed by deacetylation to produce the acceptor, which on subsequent coupling with tetramannosyl-H-phosphonate provided the fully protected PLM anchor. Final deprotection was successfully achieved by Pearlman's hydrogenation.

2.
Arch Biochem Biophys ; 685: 108332, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32194043

RESUMO

Increased tendency of cancer patients to develop venous thromboembolism (VTE) is associated with high rates of mortality. Elevation of procoagulant proteins and down regulation of naturally occurring coagulation inhibitors appears to form the basis of high risk of VTE in malignancy. A reduced level of anticoagulant protein like antithrombin (AT) will influence both coagulation and angiogenesis, as its cleaved and latent conformations show potent antiangiogenic activity. We show a concentration dependent perturbation in the secondary and tertiary structures of AT conformers exposed to hypochlorous acid (HOCl). Modulated under a very narrow concentration range of HOCl, native AT undergoes oligomerization, aggregation and fragmentation based on spectroscopic, SDS and native-PAGE studies. Factor Xa inhibition assay demonstrated a progressive decrease in inhibition activity of AT on modification by HOCl. Bis-ANS result showed that hydrophobic patches were more exposed in the case of HOCl-modified AT when assessed fluorometrically. Dosage of HOCl-modified AT in experimental animals induced high titer antibodies showing more specificity towards modified forms in comparison to unmodified forms. Auto-antibodies isolated from cancer patients also showed enhanced binding with HOCl-modified AT in comparison to native counterpart. Compared to normal AT, structurally and functionally altered conformation of HOCl-modified AT showed increased immunogenic sensitivity. HOCl modified AT can contribute to prothrombotic and angiogenic environment during cancer progression/development.

3.
Environ Sci Pollut Res Int ; 27(14): 16268-16281, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32124282

RESUMO

Acetaldehyde is a toxic, mutagenic and carcinogenic metabolite of alcohol which can bind to proteins, DNA and several other cellular macromolecules. Chronic alcohol consumption increases intracellular acetaldehyde levels which enhances the generation of reactive oxygen and nitrogen species (ROS and RNS). In this study, we have examined the effect of acetaldehyde on human erythrocytes under in vitro conditions. Treatment of human erythrocytes with different concentrations of acetaldehyde (0.05-2 mM) for 24 h at 37 °C increased intracellular generation of ROS and RNS. It also increased oxidation of proteins and lipids but decreased glutathione, total sulphhydryl and free amino group content. Methemoglobin level was increased accompanied by a decrease in methemoglobin reductase activity. Acetaldehyde impaired the antioxidant defence system and lowered the total antioxidant capacity of the cell. It decreased the activity of metabolic and membrane-bound enzymes and altered erythrocyte morphology. Our results show that acetaldehyde enhances the generation of ROS and RNS that results in oxidative modification of cellular components. This will lower the oxygen transporting ability of blood and shorten erythrocyte lifespan (red cell senescence).

4.
J Obstet Gynaecol ; : 1-5, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32013639

RESUMO

In women with a bad obstetric history, certain infections are associated with recurrent foetal loss. One of the common infectious agents is a protozoan parasite, Toxoplasma gondii. The aim of this study was to assess unpasteurised milk consumption as a potential risk factor for toxoplasmosis in females with recurrent pregnancy loss from the province of Khyber Pakhtunkhwa, Pakistan. In this study, we recruited a total of 360 females, comprising a study group of 180 females with previous history of recurrent pregnancy loss and a control group of 180 females with no such history. Blood serum from the participants was analysed for Toxoplasma gondii IgM antibodies by enzyme linked immunosorbent assay. Among the study group, 23 (12.8%) females were serologically positive for IgM antibodies against Toxoplasma gondii, whilst 157 (87.2%) were IgM negative. In the control group, only two (4.8%) females were IgM positive, whilst 178 (95.2%) were IgM negative. Bad pregnancy outcome in the study group and control group was observed to be significantly different (p < .0001). In both of these groups, unpasteurised milk consumption was found as a major risk factor for Toxoplasma gondii infection. A routine serological investigation should be carried out in pregnant women to rule out toxoplasmosis and reduce the risk of recurrent pregnancy loss as well as congenital toxoplasmosis in newborns.Impact statementWhat is already known on this subject? Seropositivity for Toxoplasma gondii antibodies ranges from 7% to 51% in different regions of the world. The prevalence rate varies because of differences in climate, culture, food habits, behaviour, personal hygiene and cooking habits of different societies and ethnic groups. Various risk factors have been identified that contribute to a high prevalence rate of the disease, including consumption of raw or poorly cooked meat, physical contact with cats or cat litter, consumption of unwashed raw vegetables and fruits, drinking of contaminated water and milk. We presumed that consuming unpasteurised milk could be a potential risk factor for developing toxoplasmosis in pregnant women.What the results of this study add? This study demonstrates high seroprevalence of Toxoplasma gondii antibodies in females of child bearing age that have consumed unpasteurised milk and is a potential risk factor for developing toxoplasmosis.What the implications are of these findings for clinical practice and/or further research? Our findings suggest that primary preventive measures (personal hygiene, frequent hand washing and consuming pasteurised milk) should be taken by health surveillance authorities to focus on families, especially pregnant women, to educate them about personal hygiene, contact with cattle or using their milk and milk products. The latter is especially important to aware them about the hazards of consuming unpasteurised and contaminated milk.

5.
Phytother Res ; 34(1): 214-226, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31657074

RESUMO

Disruption of the tightly regulated mitochondrial dynamics and energy homeostasis leads to oxidative stress and apoptotic cell death, as observed in neurodegenerative disorders such as Parkinson's disease (PD). Polyphenolic plant derivatives have been shown to alleviate such pathological features and have been used in models of neurodegenerative disorders in previous reports. In the current study, we utilized a 6-hydroxydopamine (6-OHDA) lesioned rat model of PD to explore the protective efficacy of polyphenolic phytochemical ferulic acid (FA) against mitochondrial dysfunction and explored its effect on gene and protein expression of mitochondrial dynamics regulators dynamin-related protein 1 (Drp1)/mitofusin 2 (Mfn2) in lesioned animals. We also evaluated its effect on expression of mitochondrial biogenesis regulator PGC1α and apoptotic regulators BAX, cyt c, p53, and cleaved PARP. We found that oral FA supplementation alleviated 6-OHDA induced oxidative stress, DNA fragmentation, morphological changes, and blocked apoptotic cascade. FA also reduced mitochondrial Drp1 expression and increased gene and protein expression of PGC1α, thereby regulating expression of its downstream target Mfn2 and restoring mitochondrial dynamics in lesioned animals. Our data suggest that targeting mitochondrial dynamics through modulation of PGC1α can prove to be a potent preventive strategy against PD pathology.

6.
Horm Metab Res ; 51(11): 714-722, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31683341

RESUMO

Elevated serum levels of inflammatory mediators in conditions such as PCOS reflect a low-grade chronic inflammation and this has been attributed to be associated with insulin-resistance in PCOS. Therefore, insulin-sensitizing agents are suggested to improve both reproductive as well as metabolic aspects of PCOS. This study aimed to compare the effects of metformin taken alone with that of a combination of metformin and pioglitazone on menstrual cycle, hormonal parameters, insulin resistance, and inflammatory biomarkers in women with PCOS. One hundred and six women with PCOS participated in the study. All subjects were randomized into two-arm intervention groups (Arm 1 and 2). Participants in Arm-1 received metformin (500 mg BD) daily while those in Arm-2 a combination of metformin (500 mg BD) and pioglitazone (15 mg BD) for 12 wks. Serum levels of IL-6 and IL-8 were measured using ELISA whereas insulin resistance was assessed using HOMA-IR. At baseline women with PCOS had significantly elevated circulating concentrations of IL-6 and IL-8. Treatment decreased IL-6 in both the groups, however, only the combination group showed a significant decrease (p=0.005). Serum IL-8 level had a significant decrease after treatment in both groups (p <0.001). HOMA-IR and insulin levels also decreased in both the groups (both p <0.001). Testosterone, FSH, and prolactin significantly decreased in both groups. LH also decreased in both groups, however, the change was significant only in the combination group (p=0.013). Combination of metformin and pioglitazone therapy was more effective as compared to metformin alone in reducing the levels of IL-6 and IL-8 as well as insulin resistance in PCOS.

7.
J Pak Med Assoc ; 69(11): 1628-1631, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31740868

RESUMO

OBJECTIVE: To assess and compare diagnostic value of 30-minute cortisol level over 60-minute level in the diagnosis of adrenal insufficiency. METHODS: The comparative cross-sectional study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from August 2017 to May 2018, and comprised patients referred to the facility for short synacthen test with suspicion of adrenal insufficiency. Blood samples for serum cortisol were taken at time-0 and then 30 and 60 minutes after the adreno-cortico-tropic hormone injection. Total serum cortisol was measured. Adrenal insufficiency was defined as stimulated cortisol level <500 nmol/l at 30 and 60 minutes post-stimulation. SPSS 24 was used for data analysis. RESULTS: Of the 111 subjects, 56(50.4%) were males and 55(49.5%) were females. Overall mean age was 34±20 years. Mean basal serum cortisol level was 110±98 nmol/l in patients with adrenal insufficiency and it was 294±164 nmol/l in patients with intact adrenal functions. Cortisol level at both 30 and 60 minutes was significant (p<0.001). Receiver Operating Characteristics curve was plotted which showed area under curve of 0.83 and 0.82 for 60 and 30 minutes respectively. CONCLUSIONS: The 30-minute cortisol level post-stimulation carried no diagnostic value . Measuring cortisol level once at 60-minute post-stimulation would be of more value apart from being cost-effective in the diagnosis of adrenal insufficiency.

8.
Int J Mol Sci ; 20(17)2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466256

RESUMO

One of the most chronic constraints to crop production is the grain yield reduction near the crop harvest stage by lodging worldwide. This is more prevalent in cereal crops, particularly in wheat and rice. Major factors associated with lodging involve morphological and anatomical traits along with the chemical composition of the stem. These traits have built up the remarkable relationship in wheat and rice genotypes either prone to lodging or displaying lodging resistance. In this review, we have made a comparison of our conceptual perceptions with foregoing published reports and proposed the fundamental controlling techniques that could be practiced to control the devastating effects of lodging stress. The management of lodging stress is, however, reliant on chemical, agronomical, and genetic factors that are reducing the risk of lodging threat in wheat and rice. But, still, there are many questions remain to be answered to elucidate the complex lodging phenomenon, so agronomists, breeders, physiologists, and molecular biologists require further investigation to address this challenging problem.


Assuntos
Oryza/genética , Melhoramento Vegetal/métodos , Estresse Fisiológico , Triticum/genética , Oryza/fisiologia , Característica Quantitativa Herdável , Triticum/fisiologia
9.
Nat Prod Res ; : 1-10, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31282748

RESUMO

In a continuing effort to explore the structural diversity and pharmacological activities of natural products based scaffolds, herein, we report the isolation, synthesis, and structure determination of cannabidiol and its derivatives along with their cytotoxic activities. Treatment of cannabidiol (1) with acid catalyst POCl3 afforded a new derivative 6 along with six known molecules 2 - 5, 7 and, 8. The structure of 6 was elucidated by extensive spectroscopic analyses and DFT calculations of the NMR and ECD data. All the compounds (2 - 8) were evaluated for their cytotoxic potential against a panel of eight cancer cell lines. Compounds 4, 5, 7, and 8 showed pronounced in vitro cytotoxic activity with IC50 values ranging from 5.6 to 60 µM. Out of the active molecules, compounds 4, and 7 were found to be comparable to that of the parent molecule 1 on the inhibition of almost all the tested cancer cell lines.

10.
IUBMB Life ; 71(10): 1522-1536, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31185142

RESUMO

Acetaldehyde is a metabolite of ethanol, an important constituent of tobacco pyrolysis and the aldehydic product of lipid peroxidation. Acetaldehyde induced toxicity is mainly due to its binding to cellular macromolecules resulting in the formation of stable adducts accompanied by oxidative stress. The aim of this study was to characterize structural and immunological alterations in human immunoglobulin G (IgG) modified with acetaldehyde in the presence of sodium borohydride, a reducing agent. The IgG modifications were studied by various physicochemical techniques such as fluorescence and CD spectroscopy, free amino group estimation, 2,2-azobis 2-amidinopropane (AAPH) induced red blood cell hemolysis as well as transmission electron microscopy. Molecular docking was also employed to predict the preferential binding of acetaldehyde to IgG. The immunogenicity of native and acetaldehyde-modified IgG was investigated by immunizing female New Zealand white rabbits using native and modified IgG as antigens. Binding specificity and cross reactivity of rabbit antibodies was screened by competitive inhibition ELISA and band shift assays. The modification of human IgG with acetaldehyde results in quenching of the fluorescence of tyrosine residues, decrease in free amino group content, a change in the antioxidant property as well as formation of cross-linked structures in human IgG. Molecular docking reveals strong binding of IgG to acetaldehyde. Moreover, acetaldehyde modified IgG induced high titer antibodies (>1:12800) in the experimental animals. The antibodies exhibited high specificity in competitive binding assay toward acetaldehyde modified human IgG. The results indicate that acetaldehyde induces alterations in secondary and tertiary structure of IgG molecule that leads to formation of neo-epitopes on IgG that enhances its immunogenicity.

11.
Expert Opin Drug Metab Toxicol ; 15(6): 437-447, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31100206

RESUMO

Introduction: Despite clinical efforts, pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The scarcity of effective therapies can be reflected by the lack of reliable biomarkers to adapt anticancer drugs prescription to tumors' and patients' features. Areas covered: Pharmacogenetics should provide the way to select patients who may benefit from a specific therapy that best matches individual and tumor genetic profile, but it has not yet led to gains in outcome. This review describes PDAC pharmacogenetics findings, critically reappraising studies on polymorphisms and -omics profiles correlated to response to gemcitabine, FOLFIRINOX, and nab-paclitaxel combinations, as well as limitations of targeted therapies. Further, we question whether personalized approaches will benefit patients to any significant degree, supporting the need of new strategies within well-designed trials and validated genomic tests for treatment decision-making. Expert opinion: A major challenge in PDAC is the identification of subgroups of patients who will benefit from treatments. Minimally-invasive tests to analyze biomarkers of drug sensitivity/toxicity should be developed alongside anticancer treatments. However, progress might fall below expectations because of tumor heterogeneity and clonal evolution. Whole-genome sequencing and liquid biopsies, as well as prospective validation in selected cohorts, should overcome the limitations of traditional pharmacogenetic approaches.


Assuntos
Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Farmacogenética/métodos , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Seleção de Pacientes , Prognóstico
12.
Int J Mol Sci ; 20(10)2019 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-31109052

RESUMO

Black and red rice are rich in both anthocyanin and proanthocyanin content, which belong to a large class of flavonoids derived from a group of phenolic secondary metabolites. However, the molecular pathways and mechanisms underlying the flavonoid biosynthetic pathway are far from clear. Therefore, this study was undertaken to gain insight into physiological factors that are involved in the flavonoid biosynthetic pathway in rice cultivars with red, black, and white colors. RNA sequencing of caryopsis and isobaric tags for relative and absolute quantification (iTRAQ) analyses have generated a nearly complete catalog of mRNA and expressed proteins in different colored rice cultivars. A total of 31,700 genes were identified, of which 3417, 329, and 227 genes were found specific for red, white, and black rice, respectively. A total of 13,996 unique peptides corresponding to 3916 proteins were detected in the proteomes of black, white, and red rice. Coexpression network analyses of differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) among the different rice cultivars showed significant differences in photosynthesis and flavonoid biosynthesis pathways. Based on a differential enrichment analysis, 32 genes involved in the flavonoid biosynthesis pathway were detected, out of which only CHI, F3H, ANS, and FLS were detected by iTRAQ. Taken together, the results point to differences in flavonoid biosynthesis pathways among different colored rice cultivars, which may reflect differences in physiological functions. The differences in contents and types of flavonoids among the different colored rice cultivars are related to changes in base sequences of Os06G0162500, Os09G0455500, Os09G0455500, and Os10G0536400. Current findings expand and deepen our understanding of flavonoid biosynthesis and concurrently provides potential candidate genes for improving the nutritional qualities of rice.


Assuntos
Vias Biossintéticas , Flavonoides/metabolismo , Regulação da Expressão Gênica de Plantas , Oryza/fisiologia , Proteoma , Transcriptoma , Cromatografia Líquida , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Metaboloma , Metabolômica/métodos , Proteômica/métodos , Espectrometria de Massas em Tandem
13.
J Coll Physicians Surg Pak ; 29(6): S20-S22, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31142410

RESUMO

Gastric tuberculosis is a very rare disease posing a diagnostic challenge to physicians, pathologists and radiologists. It usually occurs in females aged 25 to 45 years. Symptoms include epigastric pain, vomiting, fever, weight loss, upper gastrointestinal (GI) bleed and gastric outlet obstruction. High index of suspicion and endoscopic or endoscopic ultrasound guided biopsies may help in making an early diagnosis, particularly in patients with non-healing gastric ulcers. We report a case of gastric tuberculosis in a 55-year male, who presented with persistent vomiting, epigastric pain and significant weight loss. His upper GI endoscopy finding with histopathology results favoured the diagnosis of gastric tuberculosis. He was successfully treated with antituberculous regimen.


Assuntos
Endoscopia do Sistema Digestório/métodos , Obstrução da Saída Gástrica/etiologia , Hemorragia Gastrointestinal/etiologia , Estômago/diagnóstico por imagem , Tuberculose Gastrointestinal/diagnóstico , Antituberculosos/uso terapêutico , Obstrução da Saída Gástrica/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estômago/patologia , Resultado do Tratamento , Tuberculose Gastrointestinal/tratamento farmacológico , Vômito/etiologia
14.
Int J Mol Sci ; 20(7)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939720

RESUMO

Panicle degeneration, also known as panicle abortion, is a serious defect and causes heavy losses to reproductive yield in cereals. Several mutants have been reported to display the phenotype of spikelet abortion in rice. Recent findings have resulted in significant breakthroughs, but comprehensive understanding about the molecular pathways and physiological basis of panicle degeneration still remain a dilemma. In this review, we have summarized all the responsible genes and mechanisms underlying the panicle development with a special focus on degeneration. Here, we hypothesized a model by using knowledge and coherent logic in order to understand the molecular regulation of panicle degeneration. In addition to this, we included all the previous discoveries, schools of thoughts, ancient working theories, and crosstalk of phytohormones and provided new insights for future studies.


Assuntos
Oryza/genética , Desenvolvimento Vegetal/genética , Apoptose , Regulação da Expressão Gênica de Plantas , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Estresse Fisiológico
15.
Colloids Surf B Biointerfaces ; 180: 75-82, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31030023

RESUMO

The present study reports the fabrication of Xylan/Chitosan/Montmorillonite (MMT) composite scaffold by freeze drying process with the aim of achieving improved properties for bone tissue engineering applications. The scaffolds were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Scanning electron microscopy (SEM) and mechanical testing. The fabricated scaffolds were found to be highly porous with variations in pore size (102 µm-290 µm) on varying the filler concentration. XRD study revealed complete exfoliation of MMT incorporated in polymer conjugates (Xylan/Chitosan) prepared by Maillard reaction. In-vitro bio-mineralization study revealed significant apatite deposition on polymer matrix. Scaffolds with 5% MMT concentration exhibited needle like morphology of deposited apatite which can further provide synergistic response in increasing the mechanical properties of scaffolds when placed in contact with body fluid. The average length and thickness of apatite needles were calculated to be 140 µm and 1.2 µm respectively. The deposited apatite crystals on scaffold with 2% MMT content demonstrated Ca/P ratio of 1.67, resembling that of natural bone apatite. Swelling and biodegradation behavior of scaffold were also studied with regard to hydrophilic and barrier effect of MMT on composites. MTT assay revealed non-cytotoxic nature of scaffold with good cell viability.


Assuntos
Bentonita/química , Materiais Biocompatíveis/química , Quitosana/química , Glicoconjugados/química , Engenharia Tecidual/métodos , Xilanos/química , Bentonita/farmacologia , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quitosana/farmacologia , Glicoconjugados/farmacologia , Humanos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/fisiologia , Porosidade , Tecidos Suporte , Xilanos/farmacologia
16.
J Ayub Med Coll Abbottabad ; 31(1): 98-103, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30868793

RESUMO

BACKGROUND: Beta thalassaemia is one of the commonest genetic conditions in the world. More than 200 different mutations have been reported in the beta globin chain genes. Notably, regional and ethnic variations in most common mutations in beta-thalassaemia have been identified. It is therefore imperative that region- and ethnicity- specific commonest mutations be identified for cost-effective molecular diagnosis of ß-thalassaemia mutations. The objective of this study was to determine the molecular mutations in ß-globin chain gene in patients with thalassemia in Khyber Pakhtunkhwa (KP) using multiplex- Amplification Refractory Mutation System (ARMS) PCR. METHODS: It was a cross sectional descriptive study. Blood samples from newly diagnosed ß thalassemia patients was collected and used as source for DNA isolation. ARMS PCR was performed for detection of mutations in ß-globin gene. SDS-PAGE was conducted for visualization of the amplicon. RESULTS: Prominent mutations were Fr 8-9 (+G), CD 5 (-CT) and Fr 41-42 (-TTCT). Congenital marriages and lack of awareness are largest contributing factor for increasing the disease burden. Organomegaly being a serious clinical complication which contributes to morbidity was proportional to age and disease progression. Fr 8-9 (+G) & CD 5 (- CT) were the most frequent mutation prevalent among different ethnic groups residing in KP. CONCLUSIONS: Multiplex-ARMS PCR is capable of assessing for multiple mutations in a single tube. Regional- and ethnic- variations in the commonest mutations in KP are noted. Any mutational diagnostic strategy should consider costs and genetic variations in a particular setting..


Assuntos
Análise Mutacional de DNA/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Talassemia beta , Estudos Transversais , Humanos , Mutação/genética , Paquistão , Globinas beta/genética , Talassemia beta/diagnóstico , Talassemia beta/genética
17.
Planta ; 249(6): 1949-1962, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30895446

RESUMO

MAIN CONCLUSION: Tripsacum dactyloides is closely related to Zea mays since Zea perennis and the MTP tri- species hybrid have four possible reproductive modes. Eastern gamagrass (Tripsacum dactyloides L.) and tetraploid perennial teosinte (Zea perennis) are well known to possess genes conferring resistance against biotic and abiotic stresses as well as adaptation to flood and aluminum toxic soils. However, plant breeders have been hampered to utilize these and other beneficial traits for maize improvement due to sterility in their hybrids. By crossing a tetraploid maize-inbred line × T. dactyloides, a female fertile hybrid was produced that was crossed with Z. perennis to yield a tri-genomic female fertile hybrid, which was backcrossed with diploid maize to produce BC1 and BC2. The tri-genomic hybrid provided a new way to transfer genetic material from both species into maize by utilizing conventional plant breeding methods. On the basis of cytogenetic observations using multi-color genomic in situ hybridization, the progenies were classified into four groups, in which chromosomes could be scaled both up and down with ease to produce material for varying breeding and genetic purposes via apomixis or sexual reproduction. In the present study, pathways were found to recover maize and to obtain specific translocations as well as a speedy recovery of the T. dactyloides-maize addition line in a second backcross generation. However, phenotypes of the recovered maize were in most cases far from maize as a result of genetic load from T. dactyloides and Z. perennis, and could not be directly used as a maize-inbred line but could serve as an intermediate material for maize improvement. A series of hybrids was produced (having varying chromosome number, constitution, and translocations) with agronomic traits from all three parental species. The present study provides an application of overcoming the initial interspecific barriers among these species. Moreover, T. dactyloides is closely related to Z. mays L. ssp. mays since Z. perennis and the MTP tri- species hybrid have four possible reproductive modes.


Assuntos
Cromossomos de Plantas/genética , Fluxo Gênico , Especiação Genética , Genoma de Planta/genética , Poaceae/genética , Zea mays/genética , Apomixia , Quimera , Segregação de Cromossomos , Hibridização In Situ , Fenótipo , Melhoramento Vegetal , Poliploidia , Reprodução , Translocação Genética
18.
Bioorg Med Chem Lett ; 29(9): 1043-1046, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30871771

RESUMO

Neuropathic pain is a debilitating form of treatment-resistant chronic pain caused by damage to the nervous system. Cannabinoids have been known for suppressing neuropathic pain by modulating the endo cannabinoid system. Since the canonical Wnt/ß-catenin signaling has recently been implicated in pain sensation, we investigated the impact of major cannabinoids (1-6) from the leaves of Cannabis sativa and an epoxy derivative of compound 2, here upon referred to as 2a, on modulating Wnt/ß-catenin signaling pathway. The results presented in this study show that compound 1, 2 and 2a exhibited potent inhibitory activity against Wnt/ß-catenin pathway in a dose-dependent manner. Compound 2a was seen to inhibit this pathway at slightly lower concentrations than its parent molecule 2, under similar conditions. Taken together, compound 1, 2 and 2a, by virtue of their inhibition of Wnt/ß-catenin signaling pathway, could be developed as effective neuroprotective agents for the management of neuropathic pain.


Assuntos
Canabinoides/química , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Cannabis/química , Cannabis/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neuralgia/tratamento farmacológico , Neuralgia/patologia , Folhas de Planta/química , Folhas de Planta/metabolismo
19.
Int J Mol Sci ; 20(4)2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30781763

RESUMO

Salinity is an ever-present major constraint and a major threat to legume crops, particularly in areas with irrigated agriculture. Legumes demonstrate high sensitivity, especially during vegetative and reproductive phases. This review gives an overview of legumes sensitivity to salt stress (SS) and mechanisms to cope with salinity stress under unfavorable conditions. It also focuses on the promising management approaches, i.e., agronomic practices, breeding approaches, and genome editing techniques to improve performance of legumes under SS. Now, the onus is on researchers to comprehend the plants physiological and molecular mechanisms, in addition to various responses as part of their stress tolerance strategy. Due to their ability to fix biological nitrogen, high protein contents, dietary fiber, and essential mineral contents, legumes have become a fascinating group of plants. There is an immense need to develop SS tolerant legume varieties to meet growing demand of protein worldwide. This review covering crucial areas ranging from effects, mechanisms, and management strategies, may elucidate further the ways to develop SS-tolerant varieties and to produce legume crops in unfavorable environments.


Assuntos
Grão Comestível/fisiologia , Fabaceae/fisiologia , Estresse Salino/fisiologia , Antioxidantes/metabolismo , Modelos Biológicos , Salinidade
20.
Int J Mol Sci ; 20(4)2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30781829

RESUMO

RAD51 (DNA repair gene) family genes play ubiquitous roles in immune response among species from plants to mammals. In this study, we cloned the ZmRAD51A gene (a member of RAD51) in maize and generated ZmRAD51A overexpression (ZmRAD51A-OE) in rice, tobacco, and Arabidopsis. The expression level of ZmRAD51A was remarkably induced by salicylic acid (SA) application in maize, and the transient overexpression of ZmRAD51A in tobacco induced a hypersensitive response. The disease resistance was significantly enhanced in ZmRAD51A- OE (overexpressing) plants, triggering an increased expression of defense-related genes. High-performance liquid chromatography (HPLC) analysis showed that, compared to control lines, ZmRAD51A-OE in rice plants resulted in higher SA levels, and conferred rice plants resistance to Magnaporthe oryzae. Moreover, the ZmRAD51A-OE Arabidopsis plants displayed increased resistance to Pseudomonas syringae pv. tomato DC3000 when compared to wild types. Together, our results provide the evidence that, for the first time, the maize DNA repair gene ZmRAD51A plays an important role in in disease resistance.


Assuntos
Arabidopsis/imunologia , Reparo do DNA/genética , Resistência à Doença , Genes de Plantas , Oryza/imunologia , Doenças das Plantas/imunologia , Zea mays/genética , Arabidopsis/microbiologia , Regulação da Expressão Gênica de Plantas , Magnaporthe , Oryza/microbiologia , Doenças das Plantas/microbiologia , Folhas de Planta/fisiologia , Plantas Geneticamente Modificadas , Pseudomonas syringae/fisiologia , Ácido Salicílico/metabolismo , Tabaco/genética
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