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Antimicrobial resistance poses a significant global health threat, necessitating innovative approaches for combatting it. This review explores various mechanisms of antimicrobial resistance observed in various strains of bacteria. We examine various strategies, including antimicrobial peptides (AMPs), novel antimicrobial materials, drug delivery systems, vaccines, antibody therapies, and non-traditional antibiotic treatments. Through a comprehensive literature review, the efficacy and challenges of these strategies are evaluated. Findings reveal the potential of AMPs in combating resistance due to their unique mechanisms and lower propensity for resistance development. Additionally, novel drug delivery systems, such as nanoparticles, show promise in enhancing antibiotic efficacy and overcoming resistance mechanisms. Vaccines and antibody therapies offer preventive measures, although challenges exist in their development. Non-traditional antibiotic treatments, including CRISPR-Cas systems, present alternative approaches to combat resistance. Overall, this review underscores the importance of multifaceted strategies and coordinated global efforts to address antimicrobial resistance effectively. [ABSTRACT FROM AUTHOR]

Honeybees are vital for global crop pollination, making indispensable contributions to agricultural productivity. However, these vital insects are currently facing escalating colony losses on a global scale, primarily attributed to parasitic and pathogenic attacks. The prevalent response to combat these infections may involve the use of antibiotics. Nevertheless, the application of antibiotics raises concerns regarding potential adverse effects such as antibiotic resistance and imbalances in the gut microbiota of bees. In response to these challenges, this study reviews the utilization of a probiotic-supplemented pollen substitute diet to promote honeybee gut health, enhance immunity, and overall well-being. We systematically explore various probiotic strains and their impacts on critical parameters, including survival rate, colony strength, honey and royal jelly production, and the immune response of bees. By doing so, we emphasize the significance of maintaining a balanced gut microbial community in honeybees. The review also scrutinizes the factors influencing the gut microbial communities of bees, elucidates the consequences of dysbiosis, and evaluates the potential of probiotics to mitigate these challenges. Additionally, it delineates different delivery mechanisms for probiotic supplementation and elucidates their positive effects on diverse health parameters of honeybees. Given the alarming decline in honeybee populations and the consequential threat to global food security, this study provides valuable insights into sustainable practices aimed at supporting honeybee populations and enhancing agricultural productivity. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the potential of poly(amido amine) (PAMAM) dendrimer decorated graphene oxide (GO) based nanocarrier for targeted delivery of a hydrophobic anticancer drug, quercetin (QSR). Methods: GO-PAMAM was successfully synthesized by covalent bonding between GO and NH2-terminated PAMAM dendrimer (zero generation). To investigate drug loading performance, QSR was loaded on the surface of GO as well as GO-PAMAM. Further, the release behaviour of QSR-loaded GO-PAMAM was studied. Finally, an in-vitro sulforhodamine B assay was performed in HEK 293T epithelial cells and MDA MB 231 breast cancer cells. Key findings: It was observed that GO-PAMAM shows higher QSR loading capacity compared to GO. Also, synthesized nanocarrier exhibits controlled as well as pH-responsive release of QSR and the amount of QSR released at pH 4 was approximately two times higher than the release at pH 7.4. Furthermore, GO-PAMAM was found to be biocompatible for HEK 293T cells, and a high cytotoxic effect was observed for QSR-loaded GO-PAMAM on MDA MB 231 cells. Conclusions: The present investigation highlights the potential application of synthesized hybrid materials as a nanocarrier with excellent loading and controlled releasing efficiency for the delivery of the hydrophobic anticancer drug. Graphical Abstract [ABSTRACT FROM AUTHOR]

Drug resistance, according to World Health Organization, is one of the most serious threats to public health. This makes antibiotics ineffective and reduces their therapeutic potential. One of the most prevalent multidrug-resistant bacteria is Staphylococcus aureus which is considered to be the most common pathogen and mortality factor in both hospital and nonhospital environments worldwide. Due to an unprecedented increase in reports of drug resistance in pathogens, and also due to adverse and severe side effects of drugs, there is an urgent need to redirect scientific efforts towards search for antioxidative natural substances and other alternative sources having therapeutic potential against microbes. Natural products such as propolis seem to exhibit most promising therapeutic potential against microorganisms. Thus, present study is focused on antioxidative potential of propolis in combination with standard antibiotics ampicillin and amoxicillin against S. aureus infected BALB/c mice. For this, mice were divided into seven groups, they were decapitated after suitable experimental periods, then their liver, kidney and spleen were excised from control and experimental groups, which were homogenized and then used for different biochemical estimations following the standard protocols. Results showed that S. aureus caused severe biochemical alterations by 5th day of infection that is, lipid peroxidation increased significantly (P <0.05), reduced glutathione level and activity of antioxidant enzymes (SOD, CAT, GPx, GR, GST) decreased significantly (P <0.05) in liver, kidney and spleen of S. aureus infected mice. Ethanolic extract of propolis at a dose of 250 mg/kg body weight of mice when used alone to treat S. aureus infection gave significantly good results by 15th day of treatment. Better results were observed when propolis was used along with antibiotics. The levels of antioxidant molecules and enzymes along with liver and kidney function enzymes were restored to near normal after 15 days of treatment. So it can be concluded that propolis along with antibiotics acts as a potent free radical scavenger and can be used as a potential therapeutic agent against staphylococcal infection. [ABSTRACT FROM AUTHOR]

The study was undertaken to characterize the total phenolics, flavonoids, essential oils, quinones, tannins and antioxidant activity of 15 samples of wild Murraya koenigii (L.) Spreng. (MK) leaves obtained from different locations of Himachal Pradesh at various growth stages. The results indicated a significant variation in total phenolic content which ranged from [(170.09 ± 4.59 to 303.57 ± 7.94) in pre-flowering, (266.48 ± 7.49 to 450.01 ± 11.78) in the flowering stage, and (212.72 ± 5.37 to 363.85 ± 9.79) in fruiting stage], expressed as mg tannic acid equivalents (TAE)/g. The total flavonoid content ranged from [(15.17 ± 0.36 to 33.40 ± 0.81) in preflowering, (25.16 ± 0.67 to 58.17 ± 1.52) in flowering stage, and (17.54 ± 0.42 to 37.34 ± 0.97) in fruiting stage], expressed as mg catechin equivalent (CE)/g. Total tannin content ranged from [(75.75 ± 1.69 to 143 ± 3.74) in pre-flowering, (116 ± 3.26 to 207 ± 5.42) in the flowering stage, and (47 ± 1.18 to 156 ± 4.05) in fruiting stage], expressed as mg TAE/g. The essential oil content ranged from (0.64 ± 0.01 to 0.89 ± 0.02%) in pre-flowering, (0.85 ± 0.02 to 1 ± 0.02%) in flowering stage, and (0.54 ± 0.01 to 0.7 ± 0.01%) in fruiting stage. Quinones ranged from [(2.05 ± 0.05 to 2.97 ± 0.07) in pre-flowering, (3.07 ± 0.07 to 4.95 ± 0.13) in flowering stage, and (1.02 ± 0.02 to 1.96 ± 0.04) in fruiting stage], expressed as mM/min/g tissue. Antioxidant activity ranged from [(4.01 ± 0.09 to 7.42 ± 0.17) in pre-flowering, (8.08 ± 0.19 to 13.60 ± 0.35) in flowering stage, and (3.11 ± 0.06 to 6.37 ± 0.15) in fruiting stage], expressed as μg/ml. Data was subjected to multivariate analysis using principal component analysis (PCA), hierarchical clustering analysis (HCA). This was used for elucidating the intricate relationships between the phytochemical properties. All evaluated phytochemical parameters significantly increased during the growth transition from pre-flowering to the flowering stage, followed by their gradual decrease during the fruiting stage. The present study can serve as rationale for commercializing MK for aromatic and phytopharmaceutical industries. [ABSTRACT FROM AUTHOR]

The aim of present study was to evaluate antioxidant effect of propolis alone as well as in combination with antibiotics; ampicillin and amoxicillin against Staphylococcus aureus induced oxidative damage in spleen, by using biochemical and histopathological methods. Infection was induced in mice with S. aureus (5x106CFU/mL i.p) and protective potential of propolis against infection was evaluated by administrating 250 mg/kg body weight of propolis every day for 15 days. Mice were killed after experimental period and spleen was excised, homogenized and then used for different biochemical and histopathological estimations. Results obtained showed that lipid peroxidation level increased significantly (P <0.05), while level of reduced glutathione and activity of antioxidant enzymes (GP, GR, GST, CAT, and SOD) were decreased in spleen of S. aureus infected mice, which were increased to normal level (P <0.05) in propolis and antibiotics combination treatment. Present study also revealed that S. aureus infection caused significant change in cellular architecture of spleen as revealed by histopathological changes which were also restored to near normal after treatment with propolis and antibiotics when used in combination. These findings suggest therapeutic potential of propolis against S. aureus induced oxidative stress and histopathological damage in spleen. [ABSTRACT FROM AUTHOR]

The study was undertaken to characterize the total phenolics, flavonoids, essential oils, quinones, tannins and antioxidant activity of 15 samples of wild Murraya koenigii (L.) Spreng. (MK) leaves obtained from different locations of Himachal Pradesh at various growth stages. The results indicated a significant variation in total phenolic content which ranged from [(170.09 ± 4.59 to 303.57 ± 7.94) in pre-flowering, (266.48 ± 7.49 to 450.01 ± 11.78) in the flowering stage, and (212.72 ± 5.37 to 363.85 ± 9.79) in fruiting stage], expressed as mg tannic acid equivalents (TAE)/g. The total flavonoid content ranged from [(15.17 ± 0.36 to 33.40 ± 0.81) in preflowering, (25.16 ± 0.67 to 58.17 ± 1.52) in flowering stage, and (17.54 ± 0.42 to 37.34 ± 0.97) in fruiting stage], expressed as mg catechin equivalent (CE)/g. Total tannin content ranged from [(75.75 ± 1.69 to 143 ± 3.74) in pre-flowering, (116 ± 3.26 to 207 ± 5.42) in the flowering stage, and (47 ± 1.18 to 156 ± 4.05) in fruiting stage], expressed as mg TAE/g. The essential oil content ranged from (0.64 ± 0.01 to 0.89 ± 0.02%) in pre-flowering, (0.85 ± 0.02 to 1 ± 0.02%) in flowering stage, and (0.54 ± 0.01 to 0.7 ± 0.01%) in fruiting stage. Quinones ranged from [(2.05 ± 0.05 to 2.97 ± 0.07) in pre-flowering, (3.07 ± 0.07 to 4.95 ± 0.13) in flowering stage, and (1.02 ± 0.02 to 1.96 ± 0.04) in fruiting stage], expressed as mM/min/g tissue. Antioxidant activity ranged from [(4.01 ± 0.09 to 7.42 ± 0.17) in pre-flowering, (8.08 ± 0.19 to 13.60 ± 0.35) in flowering stage, and (3.11 ± 0.06 to 6.37 ± 0.15) in fruiting stage], expressed as µg/ml. Data was subjected to multivariate analysis using principal component analysis (PCA), hierarchical clustering analysis (HCA). This was used for elucidating the intricate relationships between the phytochemical properties. All evaluated phytochemical parameters significantly increased during the growth transition from pre-flowering to the flowering stage, followed by their gradual decrease during the fruiting stage. The present study can serve as rationale for commercializing MK for aromatic and phytopharmaceutical industries. [ABSTRACT FROM AUTHOR]

Due to emerging drug resistance in pathogenic organisms, most of the second generation antibiotics are not effective in controlling the disease. As a consequence, the dosage and duration of drug intake has increased leading to drug induced toxicity and various side effects. A large number of natural products are being reported to ameliorate the toxicity and oxidative stress caused by antibiotics. Here, we explored the antioxidative potential of honey bee product propolis alone as well as in combination with antibiotics in Staphylococcus aureus infected BALB/c mice. For experimental design, mice were divided in to seven groups and decapitated after experimental period. Kidney was excised, homogenized and then used for different biochemical and histopathological estimations. Results observed after treatment with propolis and antibiotics were compared with those of S. aureus infected group. Results showed increase in lipid peroxidation, decrease in reduced glutathione levels and antioxidant enzymes such as; catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and glutathione reductase. On the contrary, treatment with propolis, led to reduction in levels of LPO and increase in activities of antioxidant enzymes. Also, histopathology of kidney and all kidney function enzymes were restored to near normal. [ABSTRACT FROM AUTHOR]

Essential oils (EOs) extracted from aromatic plants are a potential source of several bioactive compounds. In the present study, hydro-distillation of Apium graveolens essential oil (AG-EO) was carried out and its chemical constituents were analyzed using Gas Chromatography (GC) and Gas Chromatography-Mass spectrometry (GC/MS) followed by examination of its antifungal, antioxidant, and cytotoxic potential against human breast cancer cells, MDA-MB-231. Analysis of EO resulted in the identification of nineteen (19) compounds majorly in 1,2-diphenyl-1,2-ethanediol (65.2%), 3-butyl phthalide (9.1%), limonene (6.4%), 1,1-dimethyl-1,2,3,5,7,8,9,9a-octahydro-benzocyclohepten-6-one (5.6%). Further, antifungal activity of A. graveolens EO (AG-EO) against three soil borne phytopathogenic fungal strains namely Fusarium oxysporum, Curvularia lunata, and Sclerotinia sclerotiorum showed significant mycelial growth inhibition at a concentration of 500 μg/mL with IC50 value ranging between 966-220.76 μg/mL. The antioxidant potential of EO was evaluated using dedicated spectrophotometric assays such as FRAP and DPPH. Results revealed the free radical scavenging potential of AG-EO with the value of 7.71±0.04 mM AAE/100g (for DPPH assay) and 8.31±0.03 mM AAE/100g (for FRAP assay). Additionally, the percentage of cell survival of MDA-MD-231 human breast cancer cells after treatment with EO was about 68% at 24h showing the cytotoxic effect of AG-EO against breast cancer cells whereas for non-malignant control HEK 293T cells it was about 83%. The present study indicated that the antioxidant, antifungal, and cytotoxic potential of AG-EO, a natural source of bioactive compounds, could be employed in the food, pharmaceuticals, agriculture, and cosmetics industries. However, further evaluations on animal models and clinical studies are warranted. [ABSTRACT FROM AUTHOR]

Graphene oxide (GO) has attracted tremendous attention as a most promising nanomaterial among the carbon family since it emerged as a polynomial functional tool with rational applications in diverse fields such as biomedical engineering, electrocatalysis, biosensing, energy conversion, and storage devices. Despite having certain limitations due to its irreversible aggregation performance owing largely to the strong van der Waals interactions, efforts have been made to smartly engineer its surface chemistry for realistic multimodal applications. The use of such GO-based engineered devices has increased rapidly in the last few years, principally due to its excellent properties, such as huge surface area, honeycomb-like structure allowing vacant interstitial space to accommodate compounds, sp2 hybridized carbon, improved biocompatibility and cell surface penetration due to electronic interactions. Amongst multifaceted GO dynamics, in this review, attempts are made to discuss the advanced applications of GO or graphene-based materials (GBNs) in the biomedical field involving drug or therapeutic gene delivery, dual drug or drug–gene combination targeting, special delivery of drug cocktails to the brain, stimuli-responsive release of molecular payloads, and Janus-structured smart applications for polar–nonpolar combination drug loading followed by targeting together with smart bioimaging approaches. In addition, the advantages of duel-drug delivery systems are discussed in detail. We also discuss various electronic mechanisms, and detailed surface engineering to meet microcosmic criteria for its utilization, various novel implementations of engineered GO as mentioned above, together with discussions of its inevitable toxicity or disadvantages. We hope that the target audience, belonging to biomedical engineering, pharmaceutical or material science fields, may acquire relevant information from this review which may help them design future studies in this field. [ABSTRACT FROM AUTHOR]

Background: Neem (Azadirachta indica), Tulsi (Ocimum sanctum) and Cow urine (Bos indicus) has been widely used as a therapeutic potential or additive agent in different ethnomedicinal practices as well as modern science also proved its therapeutic potential to treat various diseases and balance the body conditions. Aims: Alone study on Neem, Tulsi and Cow urine (CU) has been widely performed but this study aims to evaluate the individual as wel l as synergistic antioxidant and antibacterial activity of Neem, and Tulsi's leaves extract in different organic solvents and Cow urine. Materials and Methods: Antioxidant activity was carried out by using 2,2-Diphenyl1-picrylhydrazyl (DPPH) radical scavenging activity and the antibacterial activity was tested by the agar disc diffusion method against gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli, Proteus vulgaris and Klebsiella species) bacteria. Results: The antioxidant and antibacterial activity is concentration-dependent. The neem extract in chloroform shows the highest ZOI against S. aureus (14±2). Similarly, the neem extract in cow urine (8±0.86) and tulsi extract in methanol (8±1.04) shows the highest ZOI against E. coli. Against K. species cow urine is most effective (9±0.29) followed by neem extract in chloroform and cow urine (8±0.77). In P. vulgaris almost all sample shows ZOI around 7 mm. In synergistic antibacterial study tulsi and neem extract in cow urine shows the highest ZOI against E. coli (12±1.75) and P. vulgaris (10±1.44). The tulsi and neem extract in hexane is not effective against S. aureus and E. coli but effective in P. vulgaris and K. species (ZOI 7 mm). Tulsi and neem extract in chloroform, methanol, and cow urine show similar ZOI (9 mm). In DPPH free radical scavenging activity the methanolic extract of tulsi shows the highest inhibition of free radicle (96.35±0.001), followed by methanolic extract of neem (84.85±0.042). The fresh cow urine inhibits (25.19±0.037) followed by neem extract in chloroform (24.53±0.003), neem extract in cow urine (21.8±0.012), tulsi extract in chloroform (20.86±0.047), tulsi extract in hexane (19.5±0.031), tulsi extract in cow urine (18.33±0.023) and the least inhibition by neem extract in hexane (6.74±0.042). Conclusion: This study concludes that the neem, tulsi and cow urine has good antioxidant and antibacterial activity individually as well as synergistically and the effect is concentration-dependent. Hence the combination formulation could be a better option to study deep in the future. [ABSTRACT FROM AUTHOR]

The population of the freshwater animal was declined day by day due to the degradation of habitat and use of illegal fishing methods, which cause a great threat to these aquatic animals. The main purpose of this study was to scrutinize the wild population and fecundity of freshwater prawn Macrobrachium assamense peninsulare in Rawasan stream to assess the health status of prawn. Fecundity was estimated by a random sampling of prawn from five selected sites of Rawasan stream. A wild collection of a total of 35 ovigerous females was collected for an interval of 2 years (August 2013–July 2015) from May to September month, that is breeding session. The maximum number of eggs was 102 eggs in an individual having 52 mm total length and 2.66 g body weight. It was concluded that fecundity of Macrobrachium assamense peninsulare was low, and egg dimension was larger than other closely related species of freshwater prawn. Fecundity of Macrobrachium assamense peninsulare showed a positive relationship with a total weight (R2 = .71) and moderate with the total length (R2 = .38). A strong correlation exists between egg mass and total weight, and between egg mass and total length of female (R2 = .849 and R2 = .77 at p < .05) respectively. The numbers of eggs, that is fecundity, in a female were increased with the body growth of an individual, which results in a linear graph. [ABSTRACT FROM AUTHOR]

BACKGROUND The contribution of single nucleotide polymorphisms in transcriptional regulation of the human angiotensin receptor type I (hAT1R) gene in age-related chronic pathologies such as hypertension and associated renal disorders is not well known. The hAT1R gene has single nucleotide polymorphisms in its promoter that forms 2 haplotypes (Hap), Hap-I and Hap-II. Hap-I of AT1R gene is associated with hypertension in Caucasians. We have hypothesized here that age will alter the transcriptional environment of the cell and will regulate the expression of hAT1R gene in a haplotype-dependent manner. This could likely make subjects with Hap-I increasingly susceptible to age-associated, AT1R-mediated complications. METHOD We generated transgenic (TG) mice with Hap-I and Hap-II. Adults (10–12 weeks) and aged (20–24 months) TG male mice containing either Hap-I or Hap-II were divided into 4 groups to study (i) the age-associated and haplotype-specific transcriptional regulation of hAT1R gene and (ii) their physiological relevance. RESULTS In aged animals, TG mice with Hap-I show increased expression of hAT1R and higher blood pressure (BP); suppression of antioxidant defenses (hemoxygenase, superoxide dismutase) and antiaging molecules (ATRAP, Klotho, Sirt3); increased expression of pro-inflammatory markers (IL-6, TNFα, CRP, NOX1); and increased insulin resistance. In vivo ChIP assay shows stronger binding of transcription factor USF2 to the chromatin of Hap-I mice. CONCLUSION Our results suggest that in aged animals, as compared with Hap-II, the TG mice with Hap-I overexpress hAT1R gene due to the stronger transcriptional activity, thus resulting in an increase in their BP and associated renal disorders. [ABSTRACT FROM AUTHOR]

BACKGROUND: The transcriptional regulation of the human angiotensin receptor subtype 1 (AT1R) gene in pathophysiologies, like the metabolic syndrome, is poorly understood. The human AT1R gene has polymorphisms in its promoter that can be arranged in 2 haplotypes. Variants -810T, -713T, -214A, and -153A always occur together (Hap-I) and variants -810A, -713G, -214C, and -153G form Hap-II. We have hypothesized that high fat diet will alter cellular transcriptional milieu and increase hAT1R gene expression in a haplotype-dependent manner. This will set up an AT1Rmediated feed-forward loop promoting inflammation, oxidative stress, and hypertension in Hap-I mice. METHOD: Since Hap-I of the human AT1R gene is associated with hypertension in Caucasians, we generated transgenic (TG) mice with Hap-I and Hap-II and studied the physiological significance of high fat diet (HFD) on haplotype specific gene expression. Animals were fed with HFD for 20 weeks followed by blood pressure (BP) analysis and collection of their tissues for molecular and biochemical studies. RESULTS: After HFD treatment, as compared to Hap-II, TG mice with Hap-I show increased expression of hAT1R gene and higher BP; suppression of antioxidant defenses (HO1, SOD1) and increased expression of IL-6, TNFα, IL-1β, NOX1. In vivo ChIP assay has shown that transcription factors CEBPβ, STAT3, and USF bind more strongly to the chromatin obtained from Hap-I TG mice. CONCLUSIONS: Taken together, our results suggest, that after HFD treatment, as compared to Hap-II, the TG mice with Hap-I overexpress the AT1R gene due to the stronger transcriptional activity, thus resulting in an increase in their BP. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) in the human angiotensinogen (hAGT) gene may modulate its transcription and affect the regulation of blood pressure via activation of the renin-angiotensin aldosterone system (RAAS). In this regard, we have identified polymorphisms in the 2.5 Kb promoter of the hAGT gene that form two haplotype (Hap) blocks: -6A/G (-1670A/G, -1562C/T, -1561T/C) and -217A/G (-532T/C, -793A/G, -1074T/C & -1178G/A). hAGT gene with Hap -6A/-217A (Hap I) is associated with increased blood pressure whereas, Hap -6G/-217G (Hap II) is associated with normal blood pressure in human subjects. Since RAAS over activity contributes to hypertension in obesity, we have made transgenic mice (TG) containing either Hap I or Hap II of the hAGT gene to understand the role of obesity on its transcriptional regulation. Although, a high-fat diet (60% Kcal from fat, 12 weeks) elevates hAGT and mAGT regardless of haplotype, this effect is significantly (p<0.05) accentuated in Hap I mice, in both adipose and liver tissues. Chromatin Immuno- precipitation (ChIP) assay shows an increased binding of transcription factors including, GR, CEBPβ and STAT3 to the chromatin of the Hap I TG mice after high-fat diet as compared to Hap II TG mice (p<0.05). Differential plasma levels of hAGT in Hap II and I mice, after high-fat diet, further corroborate the variable transcriptional regulation of the hAGT, governed by gene-haplotypes. Taken together, our results show that SNPs in the Hap-I of the hAGT gene promote high-fat diet-induced binding of transcription factors GR, CEBP-β and STAT3, which lead to elevated expression of the hAGT gene in hepatic and adipose tissues. [ABSTRACT FROM AUTHOR]

Hypertension is one of the co-morbid conditions for stroke and profoundly increases its incidence. Angiotensin II (AngII) is shown to be at the center stage in driving the renin angiotensin system via activation of angiotensin 1 receptor (ATR). This makes the ATR gene one of the candidates whose differential regulation leads to the predisposition to disorders associated with hypertension. A haplotype block of four SNPs is represented primarily by haplotype-I, or Hap-I (TTAA), and haplotype-II, or Hap-II (AGCG), in the promoter of human ATR (hATR) gene. To better understand the physiological role of these haplotypes, transgenic (TG) mice containing Hap-I and Hap-II of the hATR gene in a 166-kb bacterial artificial chromosome (BAC) were generated. Mice received injection of endothelin-1 (1 mg/ml) directly in to the striatum and were evaluated for neurologic deficit scores and sacrificed for analysis of infarct volume and mRNA levels of various proteins. Mice containing Hap-I suffered from significantly higher neurological deficits and larger brain infarcts than Hap II. Similarly, the molecular analysis of oxidant and inflammatory markers in brains of mice showed a significant increase ( p < 0.05) in NOX-1 (2.3-fold), CRP (4.3-fold), and IL6 (1.9-fold) and a corresponding reduced expression of antioxidants SOD (60 %) and HO1 (55 %) in Hap-I mice as compared to Hap-II mice. These results suggest that increased expression of hATR rendered Hap-I TG mice susceptible to stroke-related pathology, possibly due to increased level of brain inflammatory and oxidative stress markers and a suppressed antioxidant defense system. [ABSTRACT FROM AUTHOR]

Purpose: Prevalence data of herpes simplex virus (HSV) in oral mucositis in children on treatment for cancer is limited. Quantitative polymerase chain reaction (PCR) has been seldom utilized for detection of HSV-1/2 in oral mucosa. Methods: Children on treatment for cancer with oral mucositis were enrolled as cases and healthy children as controls. An oral swab from the lesion in cases and mucosal scraping in controls were obtained. Both qualitative and real-time quantitative PCR for HSV-1/2 were performed. Serum ELISA-IgG/IgM for HSV-1/2 antibodies (NovaLisa™-Dietzenbach-Germany) were measured. Results: Thirty-two cases (Age, 6.3 ± 3.4 years) and 30 controls were enrolled. Majority (69 %) of cases had ALL. All patients had febrile neutropenia, except two. ELISA-IgM-HSV-1/2 was not positive in any case or control. ELISA-IgG-HSV-1/2 was positive in 11 (34 %) cases and nine (30 %) controls ( p = 1.0). Qualitative PCR for HSV-1 detected the virus in eight (25 %) cases and nil controls ( p = 0.009). HSV-2 was not detected in any case/control by qualitative PCR. Quantitative PCR detected HSV-1 in 21 (66 %) and HSV-2 in 22 (69 %) cases. In controls, quantitative PCR detected HSV-1 in three (10 %) and HSV-2 in none. In patients, the mean viral load of HSV-1 (5,500 ± 15,987 × 10 copies/nanogram DNA) was more than HSV-2 (4.03 ± 8.5 × 10) ( p = 0.11). There was no correlation of HSV-1/2 with grading of mucositis. Conclusions: Both HSV-1/2 are commonly shed from oral mucosal lesions in children receiving chemotherapy. In a novel finding, real-time PCR detected copies of HSV-2 in 69 % cases, all missed by conventional PCR. Implication for morbidity, if any, or treatment needs to be determined. [ABSTRACT FROM AUTHOR]

Background: Paediatric systemic lupus erythematosus (pSLE) exhibits an aggressive clinical phenotype with severe complications and overall poor prognosis. The aim of this study was to analyse differential expression of low molecular weight (LMW) serum protein molecules of pSLE patients with active disease in comparison to sera of healthy age matched controls. Further, some of the differential expressed spots were characterised and identified by Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) and liquid chromatography (LC-MS). Methods: 2D-PAGE was performed using pooled sera of active pSLE and age matched healthy controls. Gels were silver-stained and differentially expressed protein spots were detected by automated image master platinum 2D software. 79 ± 17 protein spots were detected for control gels and 78 ± 17 protein spots for patient gels. Of these eleven protein spots were selected randomly and characterized by MALDI-TOF MS (five protein spots) and LC MS (six protein spots) techniques. Results: Out of the 11 protein spots, 5 protein spots were significantly upregulated viz., leiomodin 2 (LMOD2); epidermal cytokeratin 2; immunoglobulin kappa light chain variable region; keratin 1 and transthyretin (TTR). Three protein spots were significantly down regulated e.g., apolipoprotein A1 (APOA1); chain B human complement component C3c; campath antibody antigen complex. Two protein spots (complement component C3; retinol binding protein (RBP) were found to be expressed only in disease and one protein spot cyclohydrolase 2 was only expressed in controls. Conclusions: We conclude that 2-D maps of patients with active pSLE and controls differ significantly. In this pilot study, using proteomic approach we have identified differential expressed proteins (of LMW) e.g., RBP, LMOD 2, TTR, Component C3c Chain B and APO A1. However, in future, further studies need to confirm the physiological and pathological role of these proteins in similar cohorts of pSLE. [ABSTRACT FROM AUTHOR]