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Biomedical subjects

Ashok Kumar

Publications and source records attributed to Ashok Kumar.

At least 19 recordsLinked to original sources
PubMed2026

Synthesis of Padina boergesenii-Derived Zinc Oxide Nanoparticles and their Therapeutic Potential Against Oral Squamous Cell Carcinoma: A Transcriptomic and in Vitro Evaluation.

Cancer remains a major health challenge, with oral squamous cell carcinoma (OSCC) being an high aggressive subtype of head and neck squamous cell carcinoma that lacks effective therapeutic options. Current study integrates the synthesis of zinc oxide nanoparticles (ZnO-NPs) from the marine brown algae Padina boergesenii with the OSCC gene expression profile to evaluate their potential therapeutic effects against OSCC. Herein, the ZnO-NPs from Padina boergesenii were prepared through the green synthesis method. The obtained ZnO-NPs were characterized through spectroscopic methods, the UV spectrophotometer shows maximum absorbance at 372 nm, FT-IR presents Zn-O functional band at 516 cm- 1, HR-TEM confirms average particle size of 55.70 nm and the Zetasizer shows zeta potential of + 12.9 mV, indicating colloidal stability. The cytotoxicity assay with ZnO-NPs against oral cancer cell lines exhibited a reduction in cell viability at IC₅₀ value of 20 µg/mL. Meanwhile, the transcriptome analysis of OSCC highlights that MYC, STAT3, BRCA1, and AKT1 are the OSCC therapeutic targets involved in proliferation, immune evasion, genomic instability, and cancer signalling pathways. Further, qRT-PCR based gene expression analysis demonstrates significant down-regulation of these targets upon ZnO-NPs treatment in KB cell lines. Overall, this study emphasizes the anticancer potential of Padina boergesenii-derived ZnO-NPs that could effectively modulate the therapeutic targets and may benefit the treatment of OSCC cancer.

Cytotoxicity↗
PubMed2003

Study of the spread of a cold instantaneous heavy gas release with surface heat transfer and variable entrainment.

Air quality models help in developing relationships between the amount of pollutant released into the ambient atmosphere by a source and the corresponding incremental contribution in the atmospheric concentration. Of the various dispersion models, the heavy gas models help in predicting the concentrations due to release of gases heavier than air and the risks associated with the increased concentrations. Several differences exist among the various models developed to study the heavy-gas dispersion phenomena. These differences mainly arise because of the varied treatment given to physical processes involved in the dispersion mechanism. One of these processes, which have not been fully considered in many of the existing models, is the effect of ground heating on the movement of a cloud under windy conditions. In this study, the box model developed by Kunsch and Fannelop (J. Hazard. Mater. 43 (1995) 169) is extended to incorporate variable air entrainment on the dispersion of a heavy gas cloud spreading in a channel under windy conditions. The air entrainment was assumed to be proportional to the cloud frontal velocity. The semi-analytical equations developed were then solved by numerical methods to provide a heavy gas cloud dispersion profile. The popular Runge-Kutta fourth order technique was adopted to solve the differential equations numerically. The model was applied on a cold cloud released instantaneously and the results indicated that the model behavior follows closely the expected dispersion trends and observed cloud characteristics reported in a laboratory study. The trial run carried out in order to model the scenario of no heat transfer, by equating the source temperature to the ambient temperature, followed variations observed in the field. The analysis of cloud behavior indicated that the cloud length is strongly influenced by source density and initial cloud temperature.

Air Movements↗
PubMed2003

Tumor necrosis factor-alpha induces functionally active hyaluronan-adhesive CD44 by activating sialidase through p38 mitogen-activated protein kinase in lipopolysaccharide-stimulated human monocytic cells.

Interaction of CD44, an adhesion molecule, with its ligand, hyaluronan (HA), in monocytic cells plays a critical role in cell migration, inflammation, and immune responses. Most cell types express CD44 but do not bind HA. The biological functions of CD44 have been attributed to the generation of the functionally active, HA-adhesive form of this molecule. Although lipopolysaccharide (LPS) and cytokines induce HA-adhesive CD44, the molecular mechanism underlying this process remains unknown. In this study, we show that LPS-induced CD44-mediated HA (CD44-HA) binding in monocytes is regulated by endogenously produced tumor necrosis factor (TNF)-alpha and IL-10. Furthermore, p38 mitogen-activated protein kinase (MAPK) activation was required for LPS- and TNF-alpha-induced, but not IL-10-induced, CD44-HA-binding in normal monocytes. To dissect the signaling pathways regulating CD44-HA binding independently of cross-regulatory IL-10-mediated effects, IL-10-refractory promonocytic THP-1 cells were employed. LPS-induced CD44-HA binding in THP-1 cells was regulated by endogenously produced TNF-alpha. Our results also suggest that lysosomal sialidase activation may be required for the acquisition of the HA-binding form of CD44 in LPS- and TNF-alpha-stimulated monocytic cells. Studies conducted to understand the role of MAPKs in the induction of sialidase activity revealed that LPS-induced sialidase activity was dependent on p42/44 MAPK-mediated TNF-alpha production. Blocking TNF-alpha production by PD98059, a p42/44 inhibitor, significantly reduced the LPS-induced sialidase activity and CD44-HA binding. Subsequently, TNF-alpha-mediated p38 MAPK activation induced sialidase activity and CD44-HA binding. Taken together, our results suggest that TNF-alpha-induced p38 MAPK activation may regulate the induction of functionally active HA-binding form of CD44 by activating sialidase in LPS-stimulated human monocytic cells.

Cell Line, Tumor↗
PubMed2003

Distinct role of ZAP-70 and Src homology 2 domain-containing leukocyte protein of 76 kDa in the prolonged activation of extracellular signal-regulated protein kinase by the stromal cell-derived factor-1 alpha/CXCL12 chemokine.

Stimulation of T lymphocytes with the ligand for the CXCR4 chemokine receptor stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12), results in prolonged activation of the extracellular signal-regulated kinases (ERK) ERK1 and ERK2. Because SDF-1alpha is unique among several chemokines in its ability to stimulate prolonged ERK activation, this pathway is thought to mediate special functions of SDF-1alpha that are not shared with other chemokines. However, the molecular mechanisms of this response are poorly understood. In this study we show that SDF-1alpha stimulation of prolonged ERK activation in Jurkat T cells requires both the ZAP-70 tyrosine kinase and the Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76) scaffold protein. This pathway involves ZAP-70-dependent tyrosine phosphorylation of SLP-76 at one or more of its tyrosines, 113, 128, and 145. Because TCR activates ERK via SLP-76-mediated activation of the linker of activated T cells (LAT) scaffold protein, we examined the role of LAT in SDF-1alpha-mediated ERK activation. However, neither the SLP-76 proline-rich domain that links to GADS and LAT, nor LAT, itself are required for SDF-1alpha to stimulate SLP-76 tyrosine phosphorylation or to activate ERK. Together, our results describe the distinct mechanism by which SDF-1alpha stimulates prolonged ERK activation in T cells and indicate that this pathway is specific for cells expressing both ZAP-70 and SLP-76.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Mechanisms by which angiotensin-converting enzyme inhibitors prevent diabetes and cardiovascular disease.

Angiotensin-converting enzyme (ACE) inhibitors are the first-line therapeutic agents for treating hypertension in patients with the cardiometabolic syndrome and those with diabetes. ACE inhibitor therapy reduces both microvascular and macrovascular complications in diabetes and appears to improve insulin sensitivity and glucose metabolism. Several recent studies indicate that ACE inhibitor therapy reduces the development of type 2 diabetes in persons with essential hypertension, a population with a high prevalence of insulin resistance. ACE inhibitor therapy has been shown to improve surrogates of cardiovascular disease (eg, vascular compliance, endothelial-derived nitric oxide production, vascular relaxation and plasma markers of inflammation, oxidative stress, and thrombosis) and reduce cardiovascular disease, renal disease progression, and stroke. This article explores potential mechanism by which ACE inhibition reduces the development of diabetes, improves these surrogate markers, and reduces cardiovascular disease and renal disease.

Angiotensin II↗
PubMed2003

CCAAT/enhancer-binding protein and activator protein-1 transcription factors regulate the expression of interleukin-8 through the mitogen-activated protein kinase pathways in response to mechanical stretch of human airway smooth muscle cells.

Here we investigated the mechanisms by which mechanical stretch regulates the production of IL-8 in primary human airway smooth muscle cells (HASMC). Bronchial HASMC were subjected to cyclic mechanical stretch (12%, 1 Hz) using the computer-controlled Flexcell Strain system. Mechanical stretch increased IL-8 mRNA expression and protein production. Cyclic stretch of HASMC also increased the kinase activities of ERK1/2, JNK1, p38, and the DNA binding activities of AP-1 and C/EBP transcription factors with little effect on NF-kappa B. The inhibition of AP-1 and C/EBP transcriptional activities blocked the production of IL-8 in culture supernatants. Furthermore, the inhibition of ERK1/2 and p38 but not JNK1 caused a significant down-regulation in the expression and production of IL-8 in response to cyclic stretch. Although protein tyrosine kinases were required for the activation of both ERK1/2 and p38 kinase, stretch-activated channels, small GTPase proteins, and extracellular Ca2+ influx were required only for the activation of p38 kinase whereas phosphoinositide 3-kinase was needed for ERK1/2 activation. In addition, the phosphorylation of ERK1/2 was essential for the activation of AP-1 whereas p38 MAP kinase was needed for the activation of C/EBP. Our data demonstrate that the cyclic stretch of HASMC causes the increased production of IL-8 by activating the AP-1 and C/EBP transcription factors through the activation of ERK1/2 and p38 kinase signaling pathways.

Binding Sites↗
PubMed2003

Inactivation of cyanobacterial nitrogenase after exposure to ultraviolet-B radiation.

Exposure of the N(2)-fixing cyanobacterium Anabaena BT2 to ultraviolet-B radiation (2.5 W m(-2)) for 30 min resulted in complete loss of nitrogenase activity but 100% cell killing occurred only after a 90-min exposure. Inactivation of nitrogenase activity was not specific to Anabaena BT2; other species also showed a similar effect. The time required for 100% killing and inactivation of nitrogenase activity differed in various species, and this difference may be ascribed to the presence of different levels of UV-B protection mechanisms in individual species. Inhibition of nitrogenase activity was immediate, since exposure of cultures to UV-B for as little as 5 min elicited some inhibition of activity. The activity of UV-B-inhibited nitrogenase did not recover upon transfer of exposed cells to fluorescent light, suggesting that the inhibition may be due to specific inactivation of the enzyme. By employment of inhibitors of protein synthesis and PS-II activity, it was demonstrated that restoration of nitrogenase activity in a UV-B-treated culture occurred by fresh synthesis of nitrogenase polypeptide. Our findings suggest that estimation of nitrogenase activity in diazotrophic species may be used as a marker enzyme for assessing the impact of UV-B radiation.

Anabaena↗
PubMed2003

Compositional difference of the exopolysaccharides produced by the virulent and virulence-deficient strains of Xanthomonas oryzae pv. oryzae.

Xanthomonas oryzae pv. oryzae, the bacterial blight pathogen of rice, is known to produce phytotoxic polysaccharides. The extracellular polysaccharide (EPS) was isolated from virulent (BXO1) and virulence-deficient gum G mutant (BXO1002) strains of X. oryzae pv. oryzae and characterized using fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR). Data from the FT-IR suggested that the aldehyde (R-CHO) group and C=O of acid anhydride are present in BXO1 but absent in BXO1002. The (1)H-NMR spectra showed the presence of an acetyl amine of hexose or pentose, free amines of glucose, an beta-anomeric carbon of hexose and pentose, hydrogen next to hydroxyl group, an acetyl amine of hexose and pentose in the polysaccharides of both BXO1 and BXO1002, and the absence of alpha-anomeric carbon of hexose or pentose and the glucuronic acid in the polysaccharides produced by BXO1002. The test for glucuronic acid also confirmed the absence of glucuronic acid in the polysaccharides of BXO1002 and the presence glucuronic acid (32 microg/mg) in the polysaccharides produced by BXO1.

Bacterial Proteins↗
PubMed2003

Effect of lycopene on pre-eclampsia and intra-uterine growth retardation in primigravidas.

OBJECTIVES: To observe the effect of the antioxidant lycopene on the occurrence of pre-eclampsia and intrauterine growth retardation in primigravida women. METHODS: A total of 251 primigravida women were enrolled in this prospective, randomized controlled study in the second trimester. A total of 116 women were given oral lycopene (Group I) in a dose of 2 mg twice daily while 135 women were given a placebo (Group II) in the same dose until delivery. The criteria for recruitment included gestational age of 16-20 weeks, singleton pregnancy, absence of any medical complication and willingness on the part of the women to participate in the study. The women were followed-up until delivery for development of pre-eclampsia, mode of delivery and fetal outcome. RESULTS: The two groups were comparable in their maternal characteristics. Pre-eclampsia developed in significantly less women in the lycopene group than in the placebo group (8.6% vs. 17.7%, P=0.043 by chi-square test). Mean diastolic blood pressure was significantly higher in the placebo group (92.2+/-5.98 mmHg vs. 86.7+/-3.80 mmHg, P=0.012). Mean fetal weight was significantly higher in the lycopene group (2751.17+/-315.76 g vs. 2657+/-444.30 g, P=0.049). The incidence of intrauterine growth retardation was significantly lower in the lycopene group than in the placebo group (12% vs. 23.7%, P=0.033). CONCLUSIONS: The results of the present study suggest that the antioxidant lycopene reduces the development of pre-eclampsia and intrauterine growth retardation in primigravida women.

Adult↗
PubMed2003

Interaction of age and chronic estradiol replacement on memory and markers of brain aging.

The current study examined effects of chronic estradiol replacement on cognition and biomarkers of aging. Young, middle-aged, and aged rats were ovariectomized and implanted with blank capsules, or capsules containing high or low doses of estradiol benzoate (EB). Three weeks later, animals were tested on inhibitory avoidance and cue and spatial discrimination on the Morris water maze. High plasma estradiol levels were associated with slower swim speed and impaired retention of inhibitory avoidance. No effect of EB treatment was observed for acquisition of the spatial discrimination task, however, a dose by age interaction was observed for retention of spatial discrimination such that higher retention scores were observed for young, middle-aged and aged animals under blank, low and high dose conditions, respectively. EB treatment reversed several hippocampal markers of age-related memory impairment, blocking induction of long-term depression and decreasing cytosolic calcineurin activity. Results indicate that the level of chronic hormone replacement interacts with age to influence hippocampal function.

Aging↗
PubMed2003

Augmentation of B7 expression by herpes simplex virus antigen.

B7 costimulation plays a major role in herpes simplex virus (HSV) immunity. Effects of immunoregulatory cytokines (interferon-gamma [IFN-gamma] and interleukin-10 [IL-10]) and HSV antigens on B7-1 (CD80) and B7-2 (CD86) expression on monocytes during HSV-2 infection were investigated using flow cytometry. Our results demonstrate that HSV-2 infection effects the expression of B7 isoforms (B7-1 and B7-2) on monocytes in two ways, with opposing outcomes. It abrogates the IFN-gamma upregulation of B7-1 and B7-2 and also augments expression of B7-1 and B7-2 on monocytes through an IFN-gamma independent mechanism. The clinical significance of these opposing effects may be related to the pathogenesis of recurrent HSV disease in immunocompetent hosts.

Antigens, CD↗
PubMed2003

Evaluation of anti-diarrhoeal activity in seed extracts of Mangifera indica.

Mangifera indica is commonly grown in many parts of the world. Its seeds have been used for anti-diarrhoeal activity in Indian traditional medicine. This study evaluates the potential anti-diarrhoeal activity of methanolic (MMI) and aqueous (AMI) extracts of seeds of M. indica in experimental diarrhoea, induced by castor oil and magnesium sulphate in mice. Both MMI and AMI were given orally in the dose of 250 mg/kg, showed significant anti-diarrhoeal activity comparable with that of the standard drug loperamide. However, only MMI significantly reduced intestinal transit in charcoal meal test as compared with atropine sulphate (5 mg/kg; im). The in vitro antimicrobial activity of MMI and AMI showed variable results. While, AMI significantly inhibited growth of Streptococcus aureus and Proteus vulgaris, both MMI and AMI did not show any significant effect on growth of E. coli and Klebsiella. The results illustrate that the extracts of M. indica have significant anti-diarrhoeal activity and part of the activity of MMI may be attributed to its effect on intestinal transit.

Animals↗
PubMed2003

Longterm survival after extended resections in patients with gallbladder cancer.

BACKGROUND: Surgery is the treatment of choice for gallbladder cancer, but the extent of resection and its benefits remain unclear. STUDY DESIGN: Survival analysis of 42 patients who underwent extended resections for gallbladder cancer was performed. Resections were labeled R0 (curative) or R1 (noncurative) based on histopathologic evaluation. Survival curves were constructed using the Kaplan-Meier method, and survival data were analyzed by univariate and multivariate analyses to identify factors associated with longterm (>2 years) survival. RESULTS: R0 status was achieved in 18 patients (43%): 100%, 100%, 45%, and 0% in stages I, II, III, and IV, respectively. Patients with R0 resections had a significantly better survival than those with R1 resections (median 25.8 months versus 17.0 months; p = 0.03). R0 status was achieved in only 3 of 20 patients (15%) with node positive (N1) disease compared with 14 of 17 patients (82%) with node negative (N0) disease. Patients with N0 disease had a significantly better survival than those with N1 disease (median not reached versus 17 months; p = 0.01). None of the patients with N1 disease survived 5 years; 5-year survival for N0 patients was 58%. Adjuvant therapy did not have a significant effect on survival. CONCLUSIONS: In patients with gallbladder cancer, R0 status could be achieved in only 43% of patients undergoing extended resections. R0 status and N0 disease were associated with better longterm survival.

Adult↗
PubMed2003

Monocyte-derived IL12, CD86 (B7-2) and CD40L expression in relapsing and progressive multiple sclerosis.

Multiple sclerosis has been postulated to be an autoimmune disease in which Th1 immune responses predominate. This response is associated with an increased production of IFNgamma and IL12 produced by T cells and by cells of the monocyte (MO) lineage, respectively. An increased expression of costimulatory molecules by T cells and antigen-presenting cells is also observed. We hypothesized that in relapsing-remitting MS (RRMS) (with or without of IFNbeta treatment) and in secondary progressive patients (SPMS) IL12 and costimulatory molecules (CD80 [B7-1], CD86 [B7-2], CD28, CD40, CD40L) would be differentially produced or expressed by MO or T cells. We performed cross-sectional and longitudinal flow cytometric studies (at monthly intervals) on peripheral blood mononuclear cells (PBMC) or on MO from SPMS or untreated and IFNbeta-treated patients with RRMS. We determined that CD86 and CD40L expression was highest on MO derived from SPMS patients compared to those from RRMS or from healthy controls (HC). In vitro culture of PBMC with recombinant human IL10, a cytokine that may be increased in response to treatment with IFNbeta and that down-regulates CD86 expression, reduced the expression of CD86 on MO derived from RRMS patients to a much higher degree compared to cells derived from SPMS or HC. In vitro secreted IL12 levels from freshly isolated MO from SPMS patients were more than 10-fold higher than either the treated or the untreated RRMS or HC. RRMS patients treated with IFNbeta demonstrated slightly lower levels of MO IL12 secretion. Our data suggest that a key mechanism in the pathogenesis of MS is the increased expression of CD86 and CD40L and the increased production of IL12 during disease progression. Part of the mechanism of action of IFNbeta may be to reduce MO CD86 and CD40L expression and IL12 secretion; failure to do so might signify either a lack of response or a transition to a more progressive phase of illness.

Adjuvants, Immunologic↗
PubMed2003

Metal chelate affinity precipitation of RNA and purification of plasmid DNA.

The affinity of metal chelates for amino acids, such as histidine, is widely used in purifying proteins, most notably through six-histidine 'tails'. We have found that metal affinity interactions can also be applied to separation of single-stranded nucleic acids through interactions involving exposed purines. Here we describe a metal affinity precipitation method to resolve RNA from linear and plasmid DNA. A copper-charged copolymer of N-isopropyl acrylamide (NIPAM) and vinyl imidazole (VI) is used to purify plasmid from an alkaline lysate of E. coli. The NIPAM units confer reversible solubility on the copolymer while the imidazole chelates metal ions in a manner accessible to interaction with soluble ligands. RNA was separated from the plasmid by precipitation along with the polymer in the presence of 800 mM NaCl. Bound RNA could be recovered by elution with imidazole and separated from copolymer by a second precipitation step. RNA binding showed a strong dependence on temperature and on the type of buffer used.

Acrylamides↗
PubMed2003

Hilar benign biliary strictures: need for subclassification.

BACKGROUND: A uniformly accepted classification allows an accurate comparison of results and formulation of a standardized treatment plan. Suggested herein is a subclassification of Bismuth type III post-cholecystectomy benign biliary strictures (BBS). METHODS: Fifty-seven patients (41%) with Bismuth type III and eight patients (6%) with type IV BBS out of a total of 139 patients with BBS were analysed retrospectively. Strictures were subclassified as type IIIA where the confluence was healthy and type III B where the roof of the confluence was healthy and right and left ductal continuity was maintained, although the floor of the confluence was scarred. RESULTS: Of 57 patients with type III BBS, 44 were subclassified as type IIIA and 13 as type IIIB. Statistically significant differences were observed in the mean operative blood loss (317 vs 635 mL, P = 0.004; 317 vs 606 mL, P = 0.006), blood transfused (0.8 vs 2.2 units, P = 0.0007; 0.8 vs 2.0 units, P = 0.0008), and duration of surgery (3.8 vs 5.1 h, P = 0.002; 3.8 vs 5.6 h; P = 0.0004) between type IIIA and IIIB, and between type IIIA and IV strictures, respectively. There were no differences in the operative parameters between type IIIB and IV strictures. There was no difference in the overall morbidity (18% vs 15% vs 25%) and septic complications among the three groups. At a mean follow up of 36.4 months, 87%, 91% and 100% of patients had excellent/good outcome in type IIIA, IIIB and IV, respectively. CONCLUSIONS: Type III biliary strictures need to be subclassified, based on whether the floor of the confluence is healthy or scarred because it influences the degree of operative difficulty and morbidity. Type IIIB BBS behave like and should be classified with type IV strictures for uniformity of result evaluation.

Adult↗
PubMed2003

Anti-inflammatory activity of some novel alpha-amino naphthalene derivatives.

alpha-Acetylamino naphthalene (1) was reacted with different aromatic aldehydes and with primary or secondary amines to give alpha-aminonaphthylsubstitutedaryl chalkones (2-5) and alpha-(substituted aminoethyl)-amidonaphthalenes (14-25), respectively. These substituted chalkones were treated with hydrazinehydrate and hydroxylamine hydrochloride to give 1-acetyl-5-substitutedaryl-3-(alpha-aminonaphthyl)-2-pyrazolines (6-9) and alpha-(2-substitutedaryl-isoxazolin-4-yl)-aminonaphthalenes (10-13), respectively. Their chemical structures were confirmed by IR and 1H-NMR spectral data and elemental analysis. Studies of the anti-inflammatory and ulcerogenic activities and acute toxicity of these newly synthesized compounds were performed in vivo and compared with the standard drug, phenylbutazone (CAS 50-33-9). Some of these compounds showed potent anti-inflammatory activity and less ulcerogenic effects than phenylbutazone.

Animals↗