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1.
J Antimicrob Chemother ; 79(1): 134-142, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-37974396

ABSTRACT

OBJECTIVES: To investigate the risk of adverse outcomes following discordant antibiotic treatment (urinary organism resistant) for culture-confirmed community-onset lower urinary tract infection (UTI). METHODS: Cohort study using routinely collected linked primary care, secondary care and microbiology data from patients with culture-confirmed community-onset lower UTI (COLUTI). Antibiotic treatment within ±3 days was considered concordant if the urinary organism was sensitive and discordant if resistant.The primary outcome was the proportion of patients experiencing urinary infection-related hospital admission (UHA) within 30 days. Secondary outcomes were the proportion of patients experiencing reconsultation within 30 days, and the odds of UHA and reconsultation following discordant treatment, adjusting for sex, age, risk factors for complicated UTI, previous antibiotic treatment, recurrent UTI and comorbidities. RESULTS: A total of 11 963 UTI episodes in 8324 patients were included, and 1686 episodes (14.1%, 95% CI 13.5%-14.7%) were discordant. UHA occurred in 212/10 277 concordant episodes (2.1%, 95% CI 1.8%-2.4%) and 88/1686 discordant episodes (5.2%, 95% CI 4.2%-6.4%). Reconsultation occurred in 3961 concordant (38.5%, 95% CI 37.6%-39.5%) and 1472 discordant episodes (87.3%, 95% CI 85.6%-88.8%). Discordant treatment compared with concordant was associated with increased odds of UHA (adjusted OR 2.31, 95% CI 1.77-3.0, P < 0.001) and reconsultation (adjusted OR 11.25, 95% CI 9.66-13.11, P < 0.001) on multivariable analysis. Chronic kidney disease and diabetes mellitus were also independently associated with increased odds of UHA. CONCLUSIONS: One in seven COLUTI episodes in primary care were treated with discordant antibiotics. In higher risk patients requiring urine culture, empirical antibiotic choice optimization could meaningfully reduce adverse outcomes.


Subject(s)
Anti-Bacterial Agents , Urinary Tract Infections , Humans , Cohort Studies , Retrospective Studies , Anti-Bacterial Agents/therapeutic use , Urinary Tract Infections/epidemiology , Comorbidity
2.
Clin Genet ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38853702

ABSTRACT

Polydactyly is a very common digit anomaly, having extra digits in hands and/or toes. Non-syndromic polydactyly in both autosomal dominant and autosomal recessive forms are caused by disease-causing variants in several genes, including GLI1, GLI3, ZNF141, FAM92A, IQCE, KIAA0825, MIPOL1, STKLD1, PITX1, and DACH1. Whole exome sequencing (WES) followed by bi-directional Sanger sequencing was performed for the single affected individual (II-1) of the family to reveal the disease causative variant/gene. 3D protein modeling and structural molecular docking was performed to determine the effect of the identified mutation on the overall protein structure. WES revealed a novel biallelic missense variant (c.472G>C; p.Ala158Pro) in exon 6 of the FAM92A gene. The identified variant segregated perfectly with the disease phenotype using Sanger sequencing. Furthermore, Insilco analysis revealed that the variant significantly changes the protein secondary structure, and substantially impact the stability of FAM92A. We report the second FAM92A disease-causing mutation associated with recessive non-syndromic postaxial polydactyly. The data further confirms the contribution of FAM92A in limb development and patterning.

3.
J Oncol Pharm Pract ; 30(1): 151-158, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37097891

ABSTRACT

BACKGROUND: Cytokine release syndrome (CRS) and immune effector cell-associated neurologic syndrome (ICANS) are well-documented toxicities of CAR T-cell therapy. To mitigate excessive toxicity, our center has formulated treatment protocols (early vs. standard) for timely management of CRS and ICANS with tocilizumab and/or corticosteroids. METHODS: This retrospective, single-center analysis included patients treated with CAR T-cell therapy. The goal was to describe the association of two management protocols with toxicity and efficacy outcomes. RESULTS: Fifty-five percent of the 40 patients assigned to early management, out of which 5% and 9% developed grade 3+ CRS and ICANS, respectively. Seventy-seven percent and 41% of these patients received tocilizumab and corticosteroids, respectively. Forty-five percent of patients were stratified as standard management, out of which 0% and 11% developed grade 3+ CRS and ICANS, respectively. Seventeen percent and 28% of these patients received tocilizumab and corticosteroids, respectively. The day +90 overall response rate (ORR) for all patients was 63%, with an ORR of 89% for those managed per early management versus 50% for those managed per standard protocol. CONCLUSION: Early use of tocilizumab and corticosteroids is effective in preventing excessive CAR-T-related toxicities with no negative impact on efficacy.


Subject(s)
Adrenal Cortex Hormones , Immunotherapy, Adoptive , Humans , Immunotherapy, Adoptive/adverse effects , Retrospective Studies , Syndrome , Adrenal Cortex Hormones/therapeutic use
4.
J Pak Med Assoc ; 74(5): 972-975, 2024 May.
Article in English | MEDLINE | ID: mdl-38783449

ABSTRACT

The current study centred on assessing the effect of various lifestyle factors (diet, physical activity [PA] level, sleep pattern, and stress level) on women's fertility. This hospitalbased comparative study was conducted at the Avicenna Medical College and Hospital, Lahore, Pakistan, with 104 females (aged 18-40 years) as participants. Half the participants had a history of infertility and 51.8% had a BMI >25. About 43% and 85% reported intake of "junk food" and "fruit and vegetable (F&V)", respectively, twice a week. DASS-21 scale endorsed "moderate-to-high-stress" in 58% of the participants. Further, moderate and intense PAable was documented in 30% and 20% of the participants. About 37% reported sleeping for ≤5 hours/day. Fertility was significantly but inversely correlated with F&V intake, stress level, and BMI. Less sleep and a sedentary lifestyle had a significantly detrimental impact on fertility. Women's fertility was positively impacted by F&V intake, moderate PA, and adequate sleep but negatively impacted by obesity and mental stress.


Subject(s)
Body Mass Index , Diet , Exercise , Life Style , Sleep , Humans , Female , Adult , Young Adult , Adolescent , Pakistan/epidemiology , Sleep/physiology , Stress, Psychological/epidemiology , Fertility , Infertility, Female/epidemiology , Sedentary Behavior , Obesity/epidemiology
5.
Biomacromolecules ; 24(10): 4444-4453, 2023 10 09.
Article in English | MEDLINE | ID: mdl-36753733

ABSTRACT

Polymeric micelles are among the most extensively used drug delivery systems. Key properties of micelles, such as size, size distribution, drug loading, and drug release kinetics, are crucial for proper therapeutic performance. Whether polymers from more controlled polymerization methods produce micelles with more favorable properties remains elusive. To address this question, we synthesized methoxy poly(ethylene glycol)-b-(N-(2-benzoyloxypropyl)methacrylamide) (mPEG-b-p(HPMAm-Bz)) block copolymers of three different comparable molecular weights (∼9, 13, and 20 kDa), via both conventional free radical (FR) and reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were subsequently employed to prepare empty and paclitaxel-loaded micelles. While FR polymers had relatively high dispersities (D ∼ 1.5-1.7) compared to their RAFT counterparts (D ∼ 1.1-1.3), they formed micelles with similar pharmaceutical properties (e.g., size, size distribution, critical micelle concentration, cytotoxicity, and drug loading and retention). Our findings suggest that pharmaceutical properties of mPEG-b-p(HPMAm-Bz) micelles do not depend on the synthesis route of their constituent polymers.


Subject(s)
Electrons , Micelles , Polymerization , Polyethylene Glycols , Polymers , Drug Carriers
6.
Appl Microbiol Biotechnol ; 107(4): 1189-1204, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36680589

ABSTRACT

Exopolysaccharides (EPSs) are biological polymers with unique structural features have gained particular interest in the fields of food, chemistry and medicine, and food industry. EPS from the food-grade lactic acid bacteria (LAB) can be used as a natural food additives to commercial ones in the processing and development of functional foods and nutraceuticals. The current study was aimed to explore the EPS-producing LAB from the dahi; to optimize the fermentation conditions through Plackett-Burman (PB) and response surface methodology (RSM); and to study its physicochemical, rheological, functional attributes, and cholesterol-lowering activity. Lactiplantibacillus paraplantarum NCCP 962 was isolated among the 08 strains screened at the initial stage. The PB design screened out four independent factors that had a significant positive effect, i.e., lactose, yeast extract, CaCl2, and tryptone, while the remaining seven had a non-significant effect. The RSM exhibited lactose, yeast extract, and CaCl2, significantly contributing to EPS yield. The maximum EPS yield (0.910 g/L) was obtained at 6.57% lactose, 0.047% yeast extract, 0.59% CaCl2, and 1.37% tryptone. The R2 value above 97% explains the higher variability and depicts the model's validity. The resulted EPS was a heteropolysaccharide in nature with mannose, glucose, and galactose monosaccharides. FTIR spectrum reflected the presence of functional groups, i.e., O-H, C-H, C = O, C-O-H, and CH2. SEM revealed a porous and rough morphology of EPS, also found to be thermally stable and negligible weight loss, i.e., 14.0% at 257 °C and 35.4% at 292.9 °C was observed in the 1st and 2nd phases, respectively. Rheological attributes revealed that strain NCCP 962 had high viscosity by increasing the EPS concentration, low pH, and temperature with respectable water holding, oil capacities, foaming abilities, and stability. NCCP 962 EPS possessed up to 46.4% reduction in cholesterol concentration in the supernatant. Conclusively, these results suggested that strain NCCP 962 can be used in food processing applications and other medical fields. KEY POINTS: • The fermentation conditions affect EPS yield from L. paraplantarum and significantly increased yield to 0.910 g/L. • The EPS was heteropolysaccharide in nature and thermally stable with amorphous morphology. • Good cholesterol-lowering potential with the best rheological, emulsifying, and foaming capacities.


Subject(s)
Lactobacillus , Lactose , Viscosity , Monosaccharides , Polysaccharides, Bacterial/chemistry
7.
J Pak Med Assoc ; 73(2): 245-248, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36800703

ABSTRACT

Objectives: To observe the effects of dietary counselling on weight management after liposuction. METHODS: The case-control study was conducted at the La Chirurgie Cosmetic Surgery Centre and Hair Transplant Institute, F-8/3, Islamabad, Pakistan, from January to July 2018, and comprised adults (100) of either gender undergoing liposuction and/or abdominoplasty who were followed for three months in the postoperative period. The subjects were divided into dietary-counselled group A, which received diet plans, and control group B, which followed up without any dietary advice. Lipid profile was done at baseline and three months post-liposuction. Data was analysed using SPSS 20. RESULTS: Of the 100 subjects enrolled, 83(83%) completed the study; 43(51.8%) in group A and 40(48.2%) in group B. Overall, there were 19(22.9%) males, 64(77.1%) females, and 55(66.3%) were aged <40 years, while 28(33.7%) were aged ≥40 years. Intra-group improvement was significant for total cholesterol, low-density lipoprotein, and triglycerides for both the groups (p<0.05). The change for very low-density lipoprotein in group B was not significant (p>0.05). Change in high-density lipoprotein was for the better in group A, while it decreased in group B and the change in both cases was significant (p<0.05). Inter-group differences were not significant (p>0.05) except for total cholesterol (p<0.05). CONCLUSIONS: Liposuction alone resulted in the improvement of lipid profile, while dietary intervention resulted in better values with respect to very low-density lipoprotein and high-density lipoprotein.


Subject(s)
Lipectomy , Adult , Female , Male , Humans , Case-Control Studies , Diet , Counseling , Lipoproteins, HDL , Lipoproteins, LDL , Lipoproteins, VLDL , Cholesterol
8.
Nutr Health ; : 2601060221144140, 2022 Dec 13.
Article in English | MEDLINE | ID: mdl-36514883

ABSTRACT

BACKGROUND: Metabolic syndrome (MetS) being a biological abnormality confers the highest risk of type 2 diabetes mellitus (T2DM). AIM: To assess MetS indicators in the newly diagnosed T2DM Pakistani population. METHODS: A cross-sectional study (N = 123) with newly diagnosed T2DM patients (gender: both, MeanAge: 49.24 ± 6.84 years) was selected from Medical OPD, Pakistan Institute of Medical Sciences, Islamabad. Basic profile, family history, and physical activity were recorded through a predesigned questionnaire, dietary intake through seven days Food Diary and Food Frequency Questionnaire. Blood pressure and selected clinical signs and symptoms were recorded. Anthropometric measurements included mid-upper arm circumference (MUAC), body mass index (BMI), waist circumference (WC), waist-and-hip ratio (WHR), waist-to-height ratio (WHtR), and conicity index. Lab parameters included fasting blood glucose, HbA1c, insulin levels, and lipid profile. Homeostatic model assessment of insulin resistance (HOMA-IR) was computed to assess insulin resistance. RESULTS: Almost all parameters related to MetS were higher than normal. The prevalence of MetS was 59.7%. BMI, MUAC, and WHtR were independently associated with HOMA-IR, but WC, WHR, and the conicity index had no relationship MetS indicators. CONCLUSION: The prevalence rate of MetS was found to be 59.7% in newly diagnosed T2DM patients. MUAC was found to be a better parameter for the diagnosis of central obesity and insulin resistance in the selected population.

9.
Int J Mol Sci ; 23(19)2022 Oct 10.
Article in English | MEDLINE | ID: mdl-36233338

ABSTRACT

Muscular dystrophies are a group of genetic muscular diseases characterized by impaired muscle regeneration, which leads to pathological inflammation that drives muscle wasting and eventually results in weakness, functional dependency, and premature death. The most known causes of death include respiratory muscle failure due to diaphragm muscle decay. There is no definitive treatment for muscular dystrophies, and conventional therapies aim to ameliorate muscle wasting by promoting physiological muscle regeneration and growth. However, their effects on muscle function remain limited, illustrating the requirement for major advancements in novel approaches to treatments, such as nanomedicine. Nanomedicine is a rapidly evolving field that seeks to optimize drug delivery to target tissues by merging pharmaceutical and biomedical sciences. However, the therapeutic potential of nanomedicine in muscular dystrophies is poorly understood. This review highlights recent work in the application of nanomedicine in treating muscular dystrophies. First, we discuss the history and applications of nanomedicine from a broader perspective. Second, we address the use of nanoparticles for drug delivery, gene regulation, and editing to target Duchenne muscular dystrophy and myotonic dystrophy. Next, we highlight the potential hindrances and limitations of using nanomedicine in the context of cell culture and animal models. Finally, the future perspectives for using nanomedicine in clinics are summarized with relevance to muscular dystrophies.


Subject(s)
Muscular Dystrophy, Duchenne , Myotonic Dystrophy , Animals , Muscle, Skeletal/pathology , Muscles/pathology , Muscular Atrophy/pathology , Muscular Dystrophy, Duchenne/drug therapy , Muscular Dystrophy, Duchenne/genetics , Myotonic Dystrophy/pathology , Nanomedicine , Pharmaceutical Preparations
10.
J Pak Med Assoc ; 72(5): 860-865, 2022 May.
Article in English | MEDLINE | ID: mdl-35713045

ABSTRACT

OBJECTIVE: To assess the pre-operative nutritional status and its effect on wound healing of patients having undergone coronary artery bypass graft surgery. Method: The hospital-based prospective study was conducted at the Armed Forces Institute of Cardiology/National Institute of Heart Disease, Rawalpindi, Pakistan, from October 2017 to March 2018, and comprised patients who underwent coronary artery bypass graft surgery. Sternal wound healing as an outcome measure was assessed with nutritional status. Investigation of dietary data focussed on various food groups and their impact on wound healing. Data was analysed using SPSS 21. RESULTS: Of the 330 patients, 16 (4.8%) died within hospital. The final sample, as such, comprised 314(95.2%) patients; 273 (86.9%) males and 42 (13.1%) females, with an overall mean age of 56.6±8.3 years. The mean body mass index was 26.9±4.3kg/m². There was non-significant relationship between body mass index and wound healing (p>0.05). Significant relationship was observed between albumin, blood glucose and wound healing (p<0.05). CONCLUSIONS: Low levels of albumin and poor blood glucose control before surgery was found to be associated with delayed wound healing. Nutritional intervention prior to coronary artery bypass graft surgery may lead to reduced risk and complications during / after surgery.


Subject(s)
Coronary Artery Bypass , Nutritional Status , Albumins , Female , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome , Wound Healing
11.
J Pak Med Assoc ; 72(1): 22-26, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35099432

ABSTRACT

OBJECTIVE: To assess the relative efficacy of flaxseed and fish oils in the management of rheumatoid arthritis. METHODS: The comparative study was conducted in the outpatient department of Rheumatology at Fatima Memorial Hospital, Shadman, Lahore, Pakistan, from July to December 2017, and comprised rheumatoid arthritis patients who were divided into group A receiving 3g/day of flaxseed oil and group B receiving 3g/day of fish oil for 90 days. Blood samples were taken at baseline and post-intervention to note the difference on biochemical parameters. Data was analysed using SPSS 21. RESULTS: Of the 60 patients, there were 30(50%) in each of the two groups. Overall, there were 8(13.3%) males and 52(86.7%) females. Both groups showed significant change in all biochemical parameters compared to baseline values (p<0.05). Intergroup comparison showed that flaxseed oil treatment was significantly more effective than fish oil treatment (p<0.05). CONCLUSIONS: While both forms of intervention were found to be effective, flaxseed oil was significantly more effective.


Subject(s)
Arthritis, Rheumatoid , Flax , Adult , Arthritis, Rheumatoid/drug therapy , Female , Fish Oils/therapeutic use , Humans , Linseed Oil , Male , Pakistan
12.
J Pak Med Assoc ; 72(10): 1942-1946, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36660979

ABSTRACT

OBJECTIVE: To study the level of physical activity of Pakistani labourers in Saudi Arabia, and to find its relationship with body mass index. Methods: The observational study was conducted inside the Pakistan Embassy in Riyadh, Saudi Arabia, from October 2017 to March 2018, and comprised Pakistani males aged 22-60 years doing unskilled and semi-skilled jobs. Body mass index was calculated, and the level of physical activity was assessed using the short form of International Physical Activity Questionnaire. Data was analysed using SPSS 20. RESULTS: There were 130 subjects with mean age of 33.53±7.9 years. There were 109(83.8%) subjects aged <40 years, and 21(16.2%) were aged >40 years. Mean body mass index of the sample was 26.13±5.29kg/m². Overall, 71(54.6%) participants were insufficiently active having energy expenditure <600 metabolic equivalent of task in minutes per week. No statistically significant result was found when total energy expenditure was considered (p>0.05), but significant result was found for energy expenditure due to 'walk alone' (p<0.05). Significant correlation was found between profession and overall energy expenditure and job-related energy expenditure. Significant but weak positive correlation was found between body mass index and walk-related energy expenditure (r=0.279), (p<0.001). CONCLUSIONS: Mean body mass index of the sample was high compared to South Asian cut-off values, and the level of physical activity was very low, but the findings failed to show an inverse relationship between physical activity level and body mass index.


Subject(s)
Body Mass Index , Exercise , Adult , Humans , Male , Cross-Sectional Studies , Exercise/physiology , Pakistan/ethnology , Saudi Arabia , Young Adult , Middle Aged
13.
Mol Ecol ; 30(15): 3815-3825, 2021 08.
Article in English | MEDLINE | ID: mdl-34008868

ABSTRACT

The continued endemicity of foot and mouth disease virus (FMDV) in East Africa has significant implications for livestock production and poverty reduction, yet its complex epidemiology in endemic settings remains poorly understood. Identifying FMDV dispersal routes and drivers of transmission is key to improved control strategies. Environmental heterogeneity and anthropogenic drivers (e.g., demand for animal products) can impact viral spread by influencing host movements. Here, we utilized FMDV serotype O VP1 genetic sequences and corresponding spatiotemporal data in order to (i) infer the recent dispersal history, and (II) investigate the impact of external factors (cattle density, human population density, proximity to livestock markets, and drought) on dispersal velocity, location, and direction of FMDV serotype O in East Africa. We identified statistical evidence of long-distance transmission events, and we found that FMDV serotype O tends to remain circulating in areas of high cattle density, high human population density, and in close proximity to livestock markets. The latter two findings highlight the influence of anthropogenic factors on FMDV serotype O spread in this region. These findings contribute to the understanding of FMDV epidemiology in East Africa and can help guide improved control measures.


Subject(s)
Foot-and-Mouth Disease Virus , Foot-and-Mouth Disease , Africa, Eastern/epidemiology , Animals , Cattle , Disease Outbreaks , Foot-and-Mouth Disease/epidemiology , Foot-and-Mouth Disease Virus/genetics , Phylogeny , Serogroup
14.
Langmuir ; 37(10): 3086-3092, 2021 03 16.
Article in English | MEDLINE | ID: mdl-33646002

ABSTRACT

Utilization of ß-carotene in functional food products is limited due to chemical instability, lower water-solubility, and higher melting point. The present research was designed to formulate a nanoemulsion system for the effective delivery of ß-carotene. ß-Carotene was successfully incorporated into nanoemulsions using the ultrasonication method. During 60 days of storage, the droplet size of ß-carotene-containing nanoemulsions varied from 112.36 to 133.9 nm at 4 °C and from 112.36 to 147.1 nm at 25 °C. The oxidation stability of olive oil was remarkably increased when incorporated into nanoemulsions. ß-Carotene nanoemulsions remained stable under varying ionic strengths (50-400 mM), pH values (2-8), and freeze-thaw cycles (four). The values of turbidity and total color difference increased over time and at a higher temperature. Degradation of ß-carotene was substantially slower in nanoemulsions, and the addition of antioxidants significantly increased the retention of ß-carotene in nanoemulsions. These findings suggest that the ultrasonic homogenization method has potential for the preparation of ß-carotene nanoemulsions with desirable properties. These nanoemulsions can be effectively used for the incorporation of ß-carotene in the food and beverage industry.


Subject(s)
Antioxidants , beta Carotene , Emulsions , Olive Oil , Solubility
15.
J Pak Med Assoc ; 71(10): 2309-2312, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34974560

ABSTRACT

OBJECTIVE: To evaluate the frequency of parasitic infections and to assess the relation between intestinal helminth infection and the anaemia status of pre-school children. METHODS: The community-based cross-sectional study was conducted in Skardu, Pakistan, from August 2016 to January 2017, and comprised pre-school children of either gender. Demographical data was collected using a structured questionnaire. Stool samples were collected and examined for the presence and differentiation of ova / larvae of different intestinal helminths under microscope at the pathology department of a local healthcare facility. Blood haemoglobin was measured from blood samples and anaemia was defined as blood Hb <11g/dL. Data was analysed using SPSS 22. RESULTS: Of the 300 paediatric subjects, 169 (56.3%) were males and 131 (43.7%) females. The overall mean age of the sample was 36±16 months. Of the total, 161(53.67%) were found infected. Among the infected, 93(31%) were males and 68(22.67%) were females (p=0.10). Among those who were infection-free, 46(15.3%) children were anaemic. CONCLUSIONS: Prevalence of helminthic infections in pre-school children in Skardu was found to be high. The public health problem needs to be addressed for the healthy development of children.


Subject(s)
Anemia , Helminthiasis , Intestinal Diseases, Parasitic , Anemia/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Feces , Female , Helminthiasis/epidemiology , Humans , Infant , Intestinal Diseases, Parasitic/complications , Intestinal Diseases, Parasitic/epidemiology , Male , Pakistan/epidemiology , Prevalence
16.
Crit Rev Food Sci Nutr ; 60(8): 1375-1387, 2020.
Article in English | MEDLINE | ID: mdl-30729798

ABSTRACT

Due to change in lifestyle and food habits, people are more at risk of diet-related diseases and cancers. It is also established that dietary modifications significantly reduce the risk of diseases. Nutrigenomics is relatively fresh discipline, but possess an enormous potential that can apply for prevention and management of certain carcinomas and diseases. This review enables us to generate useful information for scientists and health professionals regarding the role of Nutrigenomics in the prevention of diet and lifestyle-related diseases like cancer. It influences health conditions of individuals and susceptibility of disease by defining the metabolic response and gene expression. Epigenetic modifications can perform a significant role in disease occurrence and pathogenesis. DNA methylation and chromatin remodeling are the most common epigenetic mechanisms. Omega 3 fatty acids are the best example of nutrients and gene interaction not involving DNA methylation while certain bioactive food compounds have a proven role in cancer prevention through an epigenetic mechanism. Dietary polyphenols substantially take part in prevention of oral, breast, skin, esophageal, colorectal, prostate, pancreatic and lung cancers. Moreover, minerals and vitamins involve regulatory processes. Zinc, Selenium and folate involve in DNA repairing process have anticancer properties. Consumption of multivitamins prevents methylation of cancer cells.


Subject(s)
Diet , Epigenesis, Genetic , Neoplasms/genetics , Neoplasms/prevention & control , Nutrigenomics , DNA Methylation , DNA Repair/genetics , Humans
17.
Mol Cancer ; 17(1): 177, 2018 12 21.
Article in English | MEDLINE | ID: mdl-30577807

ABSTRACT

Right-sided colon cancer (RCC) has worse prognosis compared to left-sided colon cancer (LCC) and rectal cancer. The reason for this difference in outcomes is not well understood. We performed comparative somatic and proteomic analyses of RCC, LCC and rectal cancers to understand the unique molecular features of each tumor sub-types. Utilizing a novel in silico clonal evolution algorithm, we identified common tumor-initiating events involving APC, KRAS and TP53 genes in RCC, LCC and rectal cancers. However, the individual role-played by each event, their order in tumor development and selection of downstream somatic alterations were distinct in all three anatomical locations. Some similarities were noted between LCC and rectal cancer. Hotspot mutation analysis identified a nonsense mutation, APC R1450* specific to RCC. In addition, we discovered new significantly mutated genes at each tumor location, Further in silico proteomic analysis, developed by our group, found distinct central or hub proteins with unique interactomes among each location. Our study revealed significant differences between RCC, LCC and rectal cancers not only at somatic but also at proteomic level that may have therapeutic relevance in these highly complex and heterogeneous tumors.


Subject(s)
Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , Mutation/genetics , Rectal Neoplasms/genetics , Rectal Neoplasms/metabolism , Carcinogenesis/genetics , Humans , Proteogenomics/methods
18.
Curr Issues Mol Biol ; 22: 89-112, 2017.
Article in English | MEDLINE | ID: mdl-27801354

ABSTRACT

For human food security, the preservation of 7.4 million ex-situ germplasm is a global priority. However, ex-situ-conserved seeds are subject to aging, which reduces their viability and ultimately results in the loss of valuable genetic material over long periods. Recent progress in seed biology and genomics has revealed new opportunities to improve the long-term storage of ex-situ seed germplasm. This review summarizes the recent improvements in seed physiology and genomics, with the intention of developing genomic tools for evaluating seed aging. Several lines of seed biology research have shown promise in retrieving viability signal from various stages of seed germination. We conclude that seed aging is associated with mitochondrial alteration and programmed cell death, DNA and enzyme repair, anti-oxidative genes, telomere length, and epigenetic regulation. Clearly, opportunities exist for observing seed aging for developing genomic tools to increment the traditional germination test for effective conservation of ex-situ germplasm.


Subject(s)
Conservation of Natural Resources , Plants, Edible/physiology , Seeds/physiology , Aging/physiology , Plants, Edible/genetics
19.
Plant Biotechnol J ; 14(3): 976-85, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26285603

ABSTRACT

We have identified a novel means to achieve substantially increased vegetative biomass and oilseed production in the model plant Arabidopsis thaliana. Endogenous isoforms of starch branching enzyme (SBE) were substituted by either one of the endosperm-expressed maize (Zea mays L.) branching isozymes, ZmSBEI or ZmSBEIIb. Transformants were compared with the starch-free background and with the wild-type plants. Each of the maize-derived SBEs restored starch biosynthesis but both morphology and structure of starch particles were altered. Altered starch metabolism in the transformants is associated with enhanced biomass formation and more-than-trebled oilseed production while maintaining seed oil quality. Enhanced oilseed production is primarily due to an increased number of siliques per plant whereas oil content and seed number per silique are essentially unchanged or even modestly decreased. Introduction of cereal starch branching isozymes into oilseed plants represents a potentially useful strategy to increase biomass and oilseed production in related crops and manipulate the structure and properties of leaf starch.


Subject(s)
Arabidopsis/genetics , Arabidopsis/metabolism , Biomass , Plant Oils/metabolism , Seeds/growth & development , Starch/metabolism , 1,4-alpha-Glucan Branching Enzyme/metabolism , Chloroplasts/enzymology , Endosperm/metabolism , Gene Expression Regulation, Plant , Genetic Complementation Test , Phenotype , Plant Leaves/metabolism , Plants, Genetically Modified , RNA, Messenger/genetics , RNA, Messenger/metabolism , Seeds/metabolism , Transformation, Genetic , Transgenes , Zea mays/metabolism
20.
Genomics ; 104(6 Pt B): 582-6, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25269378

ABSTRACT

Streptococcus pneumoniae causes pneumonia, septicemia and meningitis. S. pneumoniae is responsible for significant mortality both in children and in the elderly. In recent years, the whole genome sequencing of various S. pneumoniae strains have increased manifold and there is an urgent need to provide organism specific annotations to the scientific community. This prompted us to develop the Streptococcus pneumoniae Genome Database (SPGDB) to integrate and analyze the completely sequenced and available S. pneumoniae genome sequences. Further, links to several tools are provided to compare the pool of gene and protein sequences, and proteins structure across different strains of S. pneumoniae. SPGDB aids in the analysis of phenotypic variations as well as to perform extensive genomics and evolutionary studies with reference to S. pneumoniae. The database will be updated at regular intervals and is freely accessible through the URL: http://pranag.physics.iisc.ernet.in/SPGDB/.


Subject(s)
Bacterial Proteins/genetics , Databases, Genetic , Genes, Bacterial , Sequence Analysis, DNA/methods , Sequence Analysis, Protein/methods , Software , Streptococcus pneumoniae/genetics , Amino Acid Sequence , Bacterial Proteins/chemistry , Base Sequence , Molecular Sequence Data , Protein Conformation
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