Formulation, Characterization and In Vitro Evaluation of Mesalamine and Bifidobacterium bifidum Loaded Hydrogel Beads in Capsule System for Colon Targeted Delivery.

Mesalamine is a first-line drug for the treatment of inflammatory bowel diseases. However, its premature release associated with marketed formulations leads to adverse effects like gastric trouble, vomiting, and diarrhoea. To minimize these side effects, colon-targeted drug delivery is essential. Besides conventional pharmacotherapy, bifidogenic probiotics with anti-inflammatory activity has been reported to elicit a significant impact on the remission of ulcerative colitis. Bifidogenic probiotics being acid-labile necessitate developing a gastro-resistant formulation for enhancing the delivery of viable cells to the colon. The present study was aimed at developing a fixed-dose unit dosage form of mucoadhesive hydrogel beads loaded with mesalamine and Bifidobacterium bifidum further encapsulated in Eudragit® capsules for the targeted drug delivery at colonic pH. The hydrogel beads were prepared by ionotropic gelation, with the effect of single and dual-crosslinking approaches on various formulation characteristics studied. Standard size 00 Eudragit® gastro-resistant capsules were prepared and the dried beads were filled inside the capsule shells. The formulation was then evaluated for various parameters, including physicochemical characterization, in vitro biocompatibility and anti-inflammatory activity. No interaction was observed between the drug and the polymers, as confirmed through FTIR, XRD, and DSC analysis. The mean particle size of the beads was ~ 457-485 µm. The optimized formulation showed a drug entrapment efficiency of 95.4 ± 2.58%. The Eudragit® capsule shells disintegrated in approximately 13 min at pH 7.4. The mucoadhesive hydrogel beads sustained the drug release above 18 h, with 50% of the drug released by the end of 12 h. The optimized formulation demonstrated significant (p < 0.05) gastro-resistance, biocompatibility, sustained drug release, cell viability, and anti-inflammatory activity.

Investigation of In Vitro Anti-cancer and Apoptotic Potential of Onion-Derived Nanovesicles Against Prostate and Cervical Cancer Cell Lines.

Plant-derived compounds have recently garnered significant interest in the field of medicine due to their rich repertoire of phytochemicals, which holds promise for exploring novel therapies to treat cancer. This study embarks on the first-time investigation of the anti-cancerous effect of onion-derived nanovesicles (ODNVs). ODNVs were isolated employing differential centrifugation followed by ultracentrifugation and subsequent characterization using dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), and Fourier transform infrared spectroscopy (FTIR). Furthermore, we delineated the anti-cancerous effect of ODNVs on two cancer cell line models HeLa (cervical cancer) and PC-3 (prostate cancer) using MTT assay, DAPI-based DNA damage using immunofluorescence microscopy, colony formation assay, migration assay, cell cycle analysis, and evaluation of apoptosis using flow cytometry and western blotting. The findings revealed dose- and time-dependent anti-proliferative effects of ODNVs on both HeLa and PC3 cell lines, accompanied by selective cytotoxicity against cancer cells. Additional results highlighted that ODNVs prevented colony growth and induced S-phase cell cycle arrest. Apoptosis induction was evaluated through alterations in nuclear morphology and the number of apoptotic cells, which increased significantly after ODNV treatment in both cancer cell lines. Furthermore, annexin V/PI staining evaluation of apoptotic cells by flow cytometry demonstrated that ODNV treatment significantly increased the number of apoptotic cells in both PC-3 and HeLa cells. Finally, Western blot analysis indicated changes in apoptosis-related proteins including bcl-2, bax, and caspase-3, emphasizing that the anti-cancerous effect of ODNVs is attributed to the induction of apoptosis and suggests the  unexplored anti-cancerous potential of ODNVs.

Investigation of in-vitro Anti-Cancer and Apoptotic Potential of Garlic-Derived Nanovesicles against Prostate and Cervical Cancer Cell Lines.

OBJECTIVE: Investigate the anti-cancerous potential of garlic-derived nanovesicles (GDNVs), exploring their cytotoxic effects on HeLa and PC-3 cell lines, and elucidate the underlying mechanisms, including apoptosis induction and inhibition of epithelial-mesenchymal transition (EMT). METHODS: GDNVs were isolated using differential centrifugation and ultracentrifugation. Characterization was performed through dynamic light scattering (DLS), field-emission scanning electron microscopy (FESEM), and Fourier-transform infrared spectroscopy (FTIR). Cytotoxicity assessments on HeLa and PC-3 cell lines using MTT assay. Apoptosis induction was evaluated through nuclear morphology changes and quantification of apoptotic cells using DAPI and PI/annexin V analysis. Western blot of apoptosis-related proteins (bcl-2, bax, caspase-3) was analysed. Anti-metastatic potential was assessed using wound healing assay and EMT transition inhibition. RESULTS: Garlic-derived nanovesicles (GDNVs), characterized by a size of 134.2 nm, demonstrated a substantial and dose- as well as time-dependent anti-proliferative impact on HeLa and PC-3 cell lines. The induction of apoptosis was unequivocally established through discernible modifications in nuclear morphology. The apoptotic cell count in HeLa and PC-3 cells increased by 42.4 ± 4.2% and 38.2 ± 3.2%, respectively. Comprehensive Western blot demonstrated alterations in the expression of key apoptotic regulators, namely bcl-2, bax, and caspase-3, providing robust evidence for the initiation of apoptosis. Furthermore, GDNVs exerted a significant inhibitory effect (p < 0.001) on the migratory potential of both HeLa and PC-3 cells. Moreover, there was a discernible association between GDNVs and the suppression of Epithelial-Mesenchymal Transition (EMT), emphasizing their role in impeding the metastatic potential of these cancer cell lines. CONCLUSION: This study establishes, for the first time, the anti-cancerous potential of GDNVs. The observed dose- and time-dependent anti-proliferative effects, selective cytotoxicity, apoptosis induction, and anti-migratory potential highlight GDNVs as a promising candidate for cancer treatment.

Production, purification, characterization, and applications of α-galactosidase from Bacillus flexus JS27 isolated from Manikaran hot springs.

α-Galactosidase hydrolyzes the α-1,6-linkage present at the non-reducing end of the sugars and results in the release of galactosyl residue from oligosaccharides like melibiose, raffinose, stachyose, etc. In the present study we report, α-galactosidase from Bacillus flexus isolated from Manikaran hot springs (India). Maximum enzyme production was obtained in guar gum and soybean meal after 72 h at 150 rpm. While, the temperature/pH of production was optimized at 50 °C and 7.0, respectively. Isoenzymes (α-gal I and II) were obtained and characterized based on temperature/pH optima along with their stability profile. JS27 α-Gal II was purified with a final purification fold of 11.54. Native and SDS-PAGE were used to determine the molecular weight of the enzyme as 86 and 41 kDa, respectively, indicating its homodimeric form. JS27 α-Gal II showed optimum enzyme activity at 55 °C and pH 7 (10 min). The enzyme displayed Km value of 2.3809 mM and Vmax of 2.0 × 104 µmol/min/ml with pNPG as substrate. JS27 α-Gal II demonstrated substrate hydrolysis and simultaneous formation of transgalactosylation products (α-GOS) with numerous substrates (sugar/sugar alcohols, oligosaccharides, and complex carbohydrates) which were verified by TLC and HPLC analysis. α-GOS are significant functional food ingredients and can be explored as prebiotics.

Physiological and molecular responses to combinatorial iron and phosphate deficiencies in hexaploid wheat seedlings.

Iron (Fe) and phosphorus (P) are the essential mineral nutrients for plant growth and development. However, the molecular interaction of the Fe and P pathways in crops remained largely obscure. In this study, we provide a comprehensive physiological and molecular analysis of hexaploid wheat response to single (Fe, P) and its combinatorial deficiencies. Our data showed that inhibition of the primary root growth occurs in response to Fe deficiency; however, growth was rescued when combinatorial deficiencies occurred. Analysis of RNAseq revealed that distinct molecular rearrangements during combined deficiencies with predominance for genes related to metabolic pathways and secondary metabolite biosynthesis primarily include genes for UDP-glycosyltransferase, cytochrome-P450s, and glutathione metabolism. Interestingly, the Fe-responsive cis-regulatory elements in the roots in Fe stress conditions were enriched compared to the combined stress. Our metabolome data also revealed the accumulation of distinct metabolites such as amino-isobutyric acid, arabinonic acid, and aconitic acid in the combined stress environment. Overall, these results are essential in developing new strategies to improve the resilience of crops in limited nutrients.

Immunohistochemical investigation of cytokine expression levels as biomarkers in transrectal ultrasound-guided needle biopsy specimens of prostate adenocarcinoma.

Cytokines influence the biological behaviour of prostate cancer (PC) and may influence patient outcome and serve as useful prognostic biomarkers. The aim of the present study was to evaluate cytokine expression levels in prostatic needle biopsy specimens and the association with clinicopathological characteristics of patients with PC. A total of 18 patients with PC who underwent transrectal ultrasound (TRUS) guided prostate biopsy were included in the clinical study. These patients were naïve to radiotherapy (RT) or androgen deprivation therapy prior to TRUS biopsy and clinical follow up data was collected. Cytokine expression levels were analysed by using immunohistochemistry and Spearman's correlation test was used to determine the correlation between cytokine expression and clinicopathological characteristics. Expression levels of pro-inflammatory TNF-α and IL-6 decreased as Gleason score (GS) increased; however, a statistically significant difference was not detected. A statically significant correlation was observed between needle biopsy specimen and pre-RT plasma sample expression levels of pro-inflammatory TNF-α and IL-6 (P=0.01 and P=0.05, respectively) and anti-inflammatory TGF-ß1 (P=0.05). However, further studies are needed to confirm these results using a larger sample size to confirm the prognostic value of pro-inflammatory TNF-α and IL-6 and anti-inflammatory TGF-ß1 in patients with PC.

Effect of Retinal Injury Induced by Laser Photocoagulation on Visuospatial Memory in Mouse Model.

Visual pathway reveals the connection between neuronal activity of the brain and eye. The neural networks of brain amplify the retinal signals resulting in the formation of visual image. The laser injury in the retina may affect the visual pathway and may lead to disruption of neuronal signals/activity. Therefore, we aimed to study the effect of retinal injury induced by laser on cognitive abilities in laser-induced mouse model. We have established laser model to understand the relation between retina and brain by disrupting retinal pigment epithelial (RPE) layer and evaluate the effect of laser-induced retinal injury on visuospatial memory. Age- and sex-matched C57BL/6J male mice were taken for conducting the experiments. The laser model was established by using laser photocoagulator to disrupt the RPE layer of the retina. After defined irradiation of laser onto mouse retina, the fundus fluorescein angiography was performed to confirm the laser spots. The visuospatial and short-term memory was performed using neurobehavioral test, that is, Morris water maze (MWM), and passive avoidance, respectively. In MWM experiment, results showed that escape latency time, which was taken by healthy and laser-injured mice was comparable. This was further validated by another neurobehavioral analysis, that is, passive avoidance that showed nonsignificant difference between these two groups using independent t -test. Visuospatial memory may not be affected by retinal injury induced by laser photocoagulation. It may depend on the power of the laser and duration of the laser. The severe injury in the retina such as optic nerve damage may cause dysfunctioning of visual pathway.

Role of Microglia and Astrocytes in Spinal Cord Injury Induced Neuropathic Pain.

Background: Spinal cord injuries incite varying degrees of symptoms in patients, ranging from weakness and incoordination to paralysis. Common amongst spinal cord injury (SCI) patients, neuropathic pain (NP) is a debilitating medical condition. Unfortunately, there remain many clinical impediments in treating NP because there is a lack of understanding regarding the mechanisms behind SCI-induced NP (SCINP). Given that more than 450,000 people in the United States alone suffer from SCI, it is unsatisfactory that current treatments yield poor results in alleviating and treating NP. Summary: In this review, we briefly discussed the models of SCINP along with the mechanisms of NP progression. Further, current treatment modalities are herein explored for SCINP involving pharmacological interventions targeting glia cells and astrocytes. Key message: The studies presented in this review provide insight for new directions regarding SCINP alleviation. Given the severity and incapacitating effects of SCINP, it is imperative to study the pathways involved and find new therapeutic targets in coordination with stem cell research, and to develop a new gold-standard in SCINP treatment.

Sugammadex-Associated Hypotension, Bradycardia, Asystole, and Death.

On December 16, 2015, the Food and Drug Administration (FDA) in the United States approved sugammadex (Bridion, Merck and Co), a modified gamma-cyclodextrin, to be used as a reversal agent. It is a first and unique selective nondepolarizing steroidal muscle relaxant (NDSMR) binding agent with a great affinity for rocuronium and vecuronium. However, there have been several recently published case reports of bradycardia and asystole immediately after sugammadex administration for the reversal. This report presents a case of sugammadex administration followed by rapidly progressing bradycardia leading to asystole and subsequent death. The family has provided the written consent to share this case report.

Levels of plasma cytokine in patients undergoing neoadjuvant androgen deprivation therapy and external beam radiation therapy for adenocarcinoma of the prostate.

BACKGROUND: Radiotherapy (RT) alone or in combination with androgen deprivation therapy (ADT) is most common non-operative treatments for localised prostate cancer (PC). Some circulatory cytokines are believed to play an important role in RT resistance and lead to tumour progression, invasion, and angiogenesis. The aim of this study is to assess the influence of ADT and RT on the expression of circulatory cytokines levels in plasma at different time points. METHODS: Between Nov 2015 and Aug 2016, 18 patients with localized PC were selected for this clinical study. All patients had received neoadjuvant ADT using a leuteinizing hormone-releasing hormone (LH-RH) analogs prior to RT. Peripheral blood samples were collected prior to ADT, before RT, at the end of RT and 3 months after the completion of RT. Blood plasma samples were monitored for the pro-inflammatory and profibrotic cytokines TNF-α, TGF-ß1, IL-6, and IL-8, using enzyme-linked immunosorbent assay (ELISA) procedures. RESULTS: The concentration of TGF-ß1 rose while IL-6 levels declined in post-ADT samples when compared pre-ADT. Levels of TGF-ß1 increased in post-RT blood plasma compared to pre-RT blood plasma. Those changes were not statically significant. Three months post-RT completion, TGF-ß1 levels decreased and IL-6 and IL-8 levels increased. Although levels of TGF-ß1, IL-6 and IL-8 were found to be altered 3 months post-RT completion, only changes in IL-8 levels were found to be statistically significant (P=0.05). CONCLUSIONS: In conclusion the changes in cytokines levels have been found after ADT and RT, which strengthen the finding of other clinical studies. Accept that small numbers of samples made difficult to attain significant results. Large clinical studies will be required to validate these findings and hopefully become useful biomarkers in the clinical setting to predict patient outcome and success of treatment received.

ANRIL rs1333049 C/G polymorphism and coronary artery disease in a North Indian population - Gender and age specific associations.

Many studies conducted worldwide substantiate a role of genetic polymorphisms in non-coding regions linked with coronary artery disease (CAD). One such single nucleotide polymorphism (SNP) of a non-coding RNA in the INK4 locus (ANRIL) i.e. rs1333049 C/G in the vicinity of cell cycle regulating genes is documented to have a role in CAD risk. In this study we aimed to determine the association of ANRIL rs1333049 C/G with CAD in a North Indian population. Five hundred disease free controls and 500 CAD patients were genotyped using allele specific ARMS-PCR method. High risk association of rs1333049 was seen in both heterozygous and mutant genotypes (OR=2.883, 95% CI=1.475-5.638 and p=0.002 and OR=6.717, 95% CI=3.444-13.102 and p < 0.001 respectively). Gender stratified analysis revealed risk association in both heterozygous and mutant genotypes in males. However, risk association in the mutant genotype and females was documented. Similarly, risk association was seen in subjects above 40 years of age in heterozygous and mutant genotypes. Similarly, risk association was reported in obese, sedentary lifestyle, positive family history and smoking in the heterozygous and mutant genotype and with diabetes in the mutant GG genotype. The study revealed high risk association of ANRIL rs1333049 with CAD and other risk factors.

Impact of Cryogenic Treatment on HCF and FCP Performance of ß-Solution Treated Ti-6Al-4V ELI Biomaterial.

The poor fatigue strength of Ti-6Al-4V ELI is a main cause of failure in structural implants. In this work, Ti-6Al-4V ELI was subjected to ß-solution treatment to obtain martensite microstructure and further subjected to -196 °C for 24 h. Significant improvement in high cycle fatigue performance of martensite Ti-6Al-4V ELI was observed on exposure to cryogenic cycle. Resistance to fatigue crack growth of alloy was augmented in martensite structure as compared with mill annealed sample and the same was retained even after exposure to cryogenic treatment. The variation observed in fatigue behavior due to cryogenic treatment was correlated with fractography and metallurgical investigations. Improvement in high cycle fatigue performance can be attributed to a combined effect of a decrease in the size of prior ß grain, formation of massive α patch and its subsequent transformation into ultra-fine α and ß during the soaking period at -196 °C.

Abrasive Wear Behavior of Cryogenically Treated Boron Steel (30MnCrB4) Used for Rotavator Blades.

Rotavator blades are prone to significant wear because of the abrasive nature of sand particles. The aim of this research work is to investigate the effect of cryogenic treatment and post tempering on abrasive wear behavior, in the presence of angular quartz sand (grain size of 212-425 µm), of rotavator blade material of boron steel (30MnCrB4). Cryogenic treatment has caused an improvement in the abrasive wear resistance and microhardness of 30MnCrB4 by 60% and 260.73%, respectively, compared to untreated material due to enhancement in hardness, the conversion of retained austenite into martensite, and the precipitation of secondary carbides in boron steel after exposure to cryogenic temperature. Economic analysis justifies the additional cost of cryogenic treatment.

Microbial production and biotechnological applications of α-galactosidase.

α-Galactosidase, (E.C. 3.2.1.22) is an exoglycosidase that target galactooligosaccharides such as raffinose, melibiose, stachyose and branched polysaccharides like galactomannans and galacto-glucomannans by catalysing the hydrolysis of α-1,6 linked terminal galactose residues. The enzyme has been isolated and characterized from microbial, plant and animal sources. This ubiquitous enzyme possesses physiological significance and immense industrial potential. Optimization of the growth conditions and efficient purification strategies can lead to a significant increase in the enzyme production. To boost commercial productivity, cloning of novel α-galactosidase genes and their heterologous expression in suitable host has gained popularity. Enzyme immobilization leads to its greater reutilization, superior thermostability, pH tolerance and increased activity. The enzyme is well explored in food industry in the removal of raffinose family oligosaccharides (RFOs) in soymilk and sugar crystallization process. It also improves animal feed quality and biomass processing. Applications of the enzyme is in the area of biomedicine includes therapeutic advances in treatment of Fabry disease, blood group conversion and removal of α-gal type immunogenic epitopes in xenotransplantation. With considerable biotechnological applications, this enzyme has been vastly commercialized and holds greater future prospects.

Integrative analysis of hexaploid wheat roots identifies signature components during iron starvation.

Iron (Fe) is an essential micronutrient for all organisms. In crop plants, Fe deficiency can decrease crop yield significantly; however, our current understanding of how major crops respond to Fe deficiency remains limited. Herein, the effect of Fe deprivation at both the transcriptomic and metabolic level in hexaploid wheat was investigated. Genome-wide gene expression reprogramming was observed in wheat roots subjected to Fe starvation, with a total of 5854 genes differentially expressed. Homoeologue and subgenome-specific analysis unveiled the induction-biased contribution from the A and B genomes. In general, the predominance of genes coding for nicotianamine synthase, yellow stripe-like transporters, metal transporters, ABC transporters, and zinc-induced facilitator-like protein was noted. Expression of genes related to the Strategy II mode of Fe uptake was also predominant. Our transcriptomic data were in agreement with the GC-MS analysis that showed the enhanced accumulation of various metabolites such as fumarate, malonate, succinate, and xylofuranose, which could be contributing to Fe mobilization. Interestingly, Fe starvation leads to a significant temporal increase of glutathione S-transferase at both the transcriptional level and enzymatic activity level, which indicates the involvement of glutathione in response to Fe stress in wheat roots. Taken together, our result provides new insight into the wheat response to Fe starvation at the molecular level and lays the foundation to design new strategies for the improvement of Fe nutrition in crops.

Cytokines expression levels from tissue, plasma or serum as promising clinical biomarkers in adenocarcinoma of the prostate: a systematic review of recent findings.

Prostate cancer (PC) is a common cancer (excluding non-melanoma skin cancer) in men in many parts of the world, although incidence and mortality rates vary significantly by population. In current medical practice, prognostic markers for PC include the presenting serum prostate-specific antigen (PSA) level, tumour Gleason score (GS) and clinical tumour stage. However, existing pre-treatment factors cannot be used to predict acute radiotherapy (RT)-induced toxicity. Therefore, new protein biomarkers are required in RT oncology to improve decision-making, treatment and therapy monitoring for PC patients. The aim of this systematic review is to the update potential research to address the difference in cytokine expression and their association with RT-induced toxicity and clinical outcomes. Studies were collected after searching three electronic databases: PubMed, Medline, and Google Scholar. An additional search was carried out through cross-check on a bibliography of selected articles. After the selection process made by two of the authors, 19 articles met the inclusion criteria and were included in the systematic review. Results from previous studies identified elevated levels of cytokines have been reported in several types of cancers and have sometimes correlated with disease progression or prognosis. Elevated levels of cytokine were noticed after immediate exposure to RT and their association with RT-induced acute/late toxicity of PC patients. Moreover, above studies also identified overexpression of cytokines on tumour biopsies and correlation with shortening cancer-specific survival and biochemical recurrence. Thus, altered levels of cytokine might be predictive biomarkers for RT-induced and clinical outcomes of PC patients.

Association of IL-8-251 A/T rs4073 and IL-10 rs1800872 -592C/A Polymorphisms and Coronary Artery Disease in North Indian Population.

CAD (Coronary Artery Disease) morbidity is becoming an endemic worldwide. Recently, the role of pro- and anti-inflammatory cytokines in the development of atherosclerotic plaques has been explored, but the association of their genetic polymorphisms and CAD has yet not been established. The present study aimed to investigate the association of IL-8-251A/T (rs4073) and IL-10 -592C/A (rs1800872) polymorphisms and the risk of CAD in North Indian population. 1000 subjects (500 angiographically confirmed CAD patients and 500 controls) were genotyped by ARMS-PCR. Results revealed a significant risk association of both the polymorphisms with CAD. The heterozygous and the mutant genotypes of IL-8 rs4073 were both found to be associated with the risk of disease after adjusting for the confounders (padj < 0.001, ORadj 3.121, 95% CI 1.926-5.056 and padj < 0.001, ORadj 3.116, 95% CI 1.952-4.973, respectively), but only the mutant AA genotype of IL-10 rs1800872 correlated with risk of disease with padj < 0.001, ORadj 4.106, 95% CI 2.160-7.806). Stratifying the samples on the basis of gender revealed CAD in heterozygous and mutant in males (padj < 0.001, ORadj 3.693, 95% CI 2.031-6.716; padj < 0.001, ORadj 3.288, 95% CI 1.848-5.851, respectively) and only the mutant to be associated with risk of disease in females (padj = 0.010, ORadj 2.867, 95% CI 1.284-6.404) for IL-8 rs4073, whereas only the mutant genotype AA of IL-10 rs1800872 associated with CAD risk in males (padj < 0.001, ORadj 5.821, 95% CI 2.831-11.970). Stratified analysis based on age showed a significant higher risk in the heterozygous and mutant genotype in subjects below 40 years of age (padj = 0.039, ORadj 5.052, 95% CI 1.081-23.602; and padj = 0.025, ORadj 5.533, 95% CI 1.239-24.704, respectively) compared with the heterozygous and mutant genotype association of the risk of disease in subjects above 40 years of age (padj < 0.000, ORadj 2.964, 95% CI 1.747-5.027; and padj < 0.000, ORadj 2.859, 95% CI 1.716-4.762, respectively) in IL-8 rs4073. For IL-10 rs1800872, risk association was seen only in subjects above 40 years of age (padj < 0.001, ORadj 5.049, and 95% CI 2.414-10.561). The present study exhibited associations of IL-8-251A/T (rs4073) and IL-10 -592C/A (rs1800872) with CAD in the North Indian population and also that the associations are gender and age dependent.

A novel study to examine the association of PCSK9 rs505151 polymorphism and coronary artery disease in north Indian population.

There is a drastic increase in the number of people suffering from coronary artery disease (CAD) worldwide with Indians being no exception. Being a developing country and experiencing a dramatic shift in lifestyle and eating habits, urbanization and industrialization, all these factors have collectively predisposed the Indian population towards CAD and the prevalence data arequite alarming. Genetic studies have disclosed the role of genes in CAD susceptibility and severity. One such gene is proprotein convertase subtilisin/kexin type 9 (PCSK9) which is sought to modulate the cholesterol levels and hence, has implications in CAD. We aim to explore the association of PCSK9 A/G (rs505151) polymorphism and hence, the susceptibility towards CAD in the north Indian population. Five-hundred angiographically confirmed CAD patients and 500 healthy individuals as control were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis revealed a significant association with the G allele with odds ratio (OR)=1.50, 95% confidence interval (CI)=1.22-1.85 and P=0.000. Also, a strong association was observedfor CAD risk with OR=1.590, 95% CI=1.106-2.284 and P=0.012. However, the homozygous GG mutant genotype was found to be completely absent from our population. Analysis of the dominant model also revealed an association with CAD risk. Our work demonstrated for the first time the association of PCSK9 A/G (rs505151) polymorphism with CAD risk in the north Indian population.

Interaction between ALOX15 polymorphisms and coronary artery disease in North Indian population.

BACKGROUND: Coronary artery disease (CAD) is major cause of death and morbidity worldwide. Arachidonate 12/15-lipoxygenase (ALOX) is a member of the lipid peroxidizing enzyme family and implicated in the pathogenesis of atherosclerosis, but with contradicting results. AIM: The present study aimed to investigate the association of two polymorphisms in ALOX15 (rs2619112 and rs7217186) and the risk of CAD in North Indian population. METHODS: A total of 500 angiographically confirmed CAD patients and 500 control subjects of North Indian population were recruited in the case-control study and genotyped by PCR-RFLP. RESULTS: The data showed a significant association between the two polymorphisms and CAD. Multiple logistic regression revealed heterozygous genotype of both the polymorphisms viz. GA of rs2619112 and CT of rs7217186 to be associated with significant high risk of CAD after adjustment for confounders (p = 0.034, OR = 2.274, 95% CI (1.062-4.870) and p = 0.000, OR = 3.407, 95% CI (2.092-5.548) respectively). Stratified analysis based on gender showed GA and AA of rs2619112 each significantly increased the risk of CAD in females (p = 0.001, OR = 13.120, CI = 2.780-61.928; p = 0.028, OR = 5.393, CI = 1.196-24.316 respectively) whereas only GA increased CAD risk in males (p = 0.005, OR = 2.277, CI = 1.290-4.020). In case of rs7217186, CT and TT showed a significant high risk of CAD in males (p = 0.000, OR = 4.048, CI = 2.678-6.119; p = 0.000, OR = 2.861, CI = 1.928-4.245). CONCLUSION: The present study shows that rs7217186:C > T and rs2619112:G > A of ALOX15 are associated with increased risk of CAD in the North Indian population.