Anticancer Potential of Pineapple and its Bioactive Compound Bromelain.

Various ailments have been treated with pineapple [Ananas comosus (L.) Merr.] throughout medicinal history. Pineapple and its bioactive compound bromelain possess health-promoting benefits. Detailed information on the chemotherapeutic activities of pineapple and its bioactive compound bromelain is provided in this review, which analyses the current literature regarding their therapeutic potential in cancer. Research on disease models in cell cultures is the focus of much of the existing research. Several studies have demonstrated the benefits of pineapple extract and bromelain for in vitro and in vivo cancer models. Preliminary animal model results show promise, but they must be translated into the clinical setting. Research on these compounds represents a promising future direction and may be well-tolerated.

Interplay of inflammatory biomarkers in heart disease patients with depressive symptoms: An update.

The pathophysiological mechanisms that connect heart disease and depressive disorders have been identified as abnormal endothelial function, dysregulation of the Hypothalamic Pituitary Adrenal (HPA) axis and abnormal platelet activities. Among these mechanisms, both endothelial dysfunction and HPA axis dysregulation are influenced by low grade inflammation and play significant roles in both conditions. Consequently, it is hypothesized that inflammation is an integral part of the formation of atherosclerotic plaques, linking the occurrence of heart diseases to the activation and shedding of intercellular adhesion molecules (ICAMs), especially soluble ICAM-1. This process is accompanied by the local and systemic secretion of various inflammatory markers like interleukin-6, Tumour Necrosis Factor, and C-reactive protein. Therefore, this review primarily focuses on defining the potential role of different inflammatory biomarkers in depression and heart disease and assessing whether mediators could serve as predictive biomarkers for detecting depressive symptoms in patients with heart disease.

Silicic and Humic Acid Priming Improves Micro- and Macronutrient Uptake, Salinity Stress Tolerance, Seed Quality, and Physio-Biochemical Parameters in Lentil (Lens culinaris spp. culinaris).

Lentil is an important grain legume crop which is mostly grown on marginal soils that hamper its productivity. Improvement of salt tolerance in lentils is considered to be a useful strategy of utilizing salt-affected lands in an economic manner. This study was conducted to evaluate the effectiveness of seed priming using silicic acid and humic acid both seperately and in combination to improve salt stress tolerance among three different lentil varieties: IPL-316 (tolerant), PSL-9, and PDL-1 (susceptible). The concentrations and durations of treatments were standardized under the normal condition and the salinity stress condition. Salt stress hindered seedling emergence and biomass production and accelerated Na+ toxicity and oxidative damage at the seedling stage in untreated seeds. Nevertheless, chemical priming improved early seedling emergence, increased root length, shoot length, and seed vigor index I and II, and reduced the mean germination time. A significant quantitative change in biochemical parameters under normal and salinity stress conditions was observed in IPL-316,viz. Specifically, for IPL-316, the following parameters were observed (values under the normal condition and values under salt stress conditions, respectively): chlorophyll-a (16 and 13 mg/g Fw), chlorophyll-b (25 and 16 mg/g FW), total chlorophyll content (42 and 30 mg/g FW), relative leaf water content (92% and 82%), total soluble sugars (26 and 33 ug/g FW), free amino acid (10 and 7 mg/g FW), total phenol (26 and 24 mg of GAE/g FW), total protein (35 and 29 mg/g FW), carbohydrate (208 and 173 mg/g FW), superoxide dismutase (SOD) (29 and 35 unit/min./g FW), proline (0.28 and 0.32 u mol/g FW), catalase (CAT) (84 and 196 unit/mL/g FW), and peroxidase (POX) (217 and 738 unit/mL/g FW). Furthermore, histochemical analysis of H2O2 and O2-, micronutrients, and macronutrients also increased, while malondialdehyde (MDA) (0.31 and 0.47 nmol/mL FW) content decreased using silicic and humic acid priming under salt stress conditions. The combination of silicic and humic acids improved seedling growth and reduced oxidative damage in lentil plants under salt stress conditions. The combination of silicic and humic acid priming hastened seedling emergence, seed quality parameters, and biochemical parameters under salt stress over respective control. To the best of our knowledge, this is the first report of integrated chemical priming in lentils for salinity stress. In conclusion, chemical priming using a combination of silicic and humic acid performed better in terms of seed quality due to enhanced antioxidant machinery, better membrane stability and osmolyte protection, and enhanced nutrient uptake under salt stress conditions.

Preclinical and Clinical Use of Indigenously Developed 99mTc-Diethylenetriaminepentaacetic Acid-Bis-Methionine: l-Type Amino Acid Transporter 1-Targeted Single Photon Emission Computed Tomography Radiotracer for Glioma Management.

A new era in tumor classification, diagnosis, and prognostic evaluation has begun as a consequence of recent developments in the molecular and genetic characterization of central nervous system tumors. In this newly emerging era, molecular imaging modalities are essential for preoperative diagnosis, surgical planning, targeted treatment, and post-therapy evaluation of gliomas. The radiotracers are able to identify brain tumors, distinguish between low- and high-grade lesions, confirm a patient's eligibility for theranostics, and assess post-radiation alterations. We previously synthesized and reported the novel l-type amino acid transporter 1 (LAT-1)-targeted amino acid derivative in light of the use of amino acid derivatives in imaging technologies. Further, we have developed a single vial ready to label Tc-lyophilized kit preparations of diethylenetriaminepentaacetic acid-bis-methionine [DTPA-bis(Met)], also referred to as methionine-diethylenetriaminepentaacetic acid-methionine (MDM) and evaluated its imaging potential in numerous clinical studies. This review summarizes our previous publications on 99mTc-DTPA-bis(Met) in different clinical studies such as detection of breast cancer, as a prognostic marker, in detection of recurrent/residual gliomas, for differentiation of recurrent/residual gliomas from radiation necrosis, and for comparison of 99mTc-DTPA-bis(Met) with 11C-L-methionine (11C-MET), with relevant literature on imaging modalities in glioma management.

Short-term trivalent arsenic and hexavalent chromium exposures induce gut dysbiosis and transcriptional alteration in adipose tissue of mice.

BACKGROUND: Inorganic arsenic [As(III)] and hexavalent chromium [Cr(VI)] can potentially affect metabolic functions. These heavy metal(s)/metalloids can also affect the gut microbial architecture which affects metabolic health. Here, we assessed the effects of short-term exposure of As(III) and Cr(VI) on key transcription factors in adipose tissues and on selected gut microbial abundances to understand the possible modulatory role of these toxicants on host metabolic health. METHODS AND RESULTS: qRT-PCR based relative bacterial abundance studies in cecal samples, gene expression analysis for gut wall integrity in ileum and colon and adipogenesis, lipolysis, and thermogenic genes in gonadal white and brown adipose tissue (gWAT and BAT), along with tissue oxidative stress parameters have been performed. As(III) and Cr(VI) exposure reduced beneficial Lactobacilli, Bifidobacteria, Akkermansia, Lachenospiraceae, Fecalibacterium, Eubacterium, and clostridium coccoid group while increasing lipopolysaccharides producing Enterobacteriaceae abundances. It also impaired structural features and expression of key tight junction and mucin production genes in ileum and colon (Cld-2, Cld-4, ZO-1, ZO-2, MUC-2 and - 4). In gWAT it inhibited adipogenesis (PPARγ, FASN, SREBP1a), lipolysis (HSL, ACOX-1), and thermogenesis (UCP-1, PGC1a, PRDM-16, PPARa) related genes expression, whereas in BAT, it enhanced adipogenesis and reduced thermogenesis. These exposures also reduces the endogenous antioxidants levels in these tissues and promote pro-inflammatory cytokines genes expression (TLRs, IL-6, MCP-1). The combinatorial exposure appears to have more deleterious effects. CONCLUSION: These effects of As(III) and Cr(VI) may not directly be linked to their known toxicological effects, instead, more intriguing crosstalk with gut microbial ecosystem hold the key.

Exploring the Role of Stem Cell Therapy in Treating Neurodegenerative Diseases: Challenges and Current Perspectives.

Several human neurological disorders, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, spinal cord injury, multiple sclerosis, and brain stroke, are caused by the injury to neurons or glial cells. The recent years have witnessed the successful generation of neurons and glia cells driving efforts to develop stem-cell-based therapies for patients to combat a broad spectrum of human neurological diseases. The inadequacy of suitable cell types for cell replacement therapy in patients suffering from neurological disorders has hampered the development of this promising therapeutic approach. Attempts are thus being made to reconstruct viable neurons and glial cells from different stem cells, such as embryonic stem cells, mesenchymal stem cells, and neural stem cells. Dedicated research to cultivate stem cell-based brain transplantation therapies has been carried out. We aim at compiling the breakthroughs in the field of stem cell-based therapy for the treatment of neurodegenerative maladies, emphasizing the shortcomings faced, victories achieved, and the future prospects of the therapy in clinical settings.

Expression of potential reference genes in response to macronutrient stress in rice and soybean.

Given the complexity of nutrient stress responses and the availability of a few validated reference genes, we aimed to identify robust and stable reference genes for macronutrient stress in rice and soybean. Ten potential reference genes were evaluated using geNorm, NormFinder, BestKeeper, Comparative ΔCt method, and RefFinder algorithms under low and completely starved conditions of nitrogen (N), phosphorus (P), potassium (K), and sulphur (S). Results revealed distinct sets of reference gene pairs, showing stable expression under different experimental conditions. The gene pairs TIP41/UBC(9/10/18) and F-box/UBC10 were most stable in rice and soybean, respectively under N stress. Under P stress, UBC9/UBC10 in rice and F-Box/UBC10 in soybean were most stable. Similarly, TIP41/UBC10 in rice and RING FINGER/UBC9 in soybean were the best gene pairs under K stress while F-Box/TIP41 in rice and UBC9/UBC10 in soybean were the most stable gene pairs under S stress. These reference gene pairs were validated by quantifying the expression levels of high-affinity transporters like NRT2.1/NRT2.5, PT1, AKT1, and SULTR1 for N, P, K, and S stress, respectively. This study reiterates the importance of choosing reference genes based on crop species and the experimental conditions, in order to obtain concrete answers to missing links of gene regulation in response to macronutrient deficiencies.

Proteomics and Neurodegenerative Disorders: Advancements in the Diagnostic Analysis.

Changes in protein structure and function, alteration in protein-protein interaction, and significant difference in protein concentration inside the body could play an important role in indicating the pathological evidence of abnormalities before the development of clinical symptoms and act as a critical detection and diagnostic tool commonly known as biomarkers. Biomarkers play important roles in the diagnosis of various chronic diseases, including cancer. Neurodegenerative disorders, including Parkinson's, Alzheimer's, Huntington's, prion, and multiple sclerosis, are well characterized by neuronal deterioration, resulting in precise modifications of neuronal proteins. Nowadays, the diagnosis of neurological disorders is based on proteins or biomarkers. These biomarkers may be found in the cerebrospinal fluid, blood, serum, plasma, saliva, or urine sample. Early diagnosis is urgently needed to prevent further damage. For early diagnosis, identifying the changes in novel protein levels and their functions under the disease conditions is necessary. These can be used as specific proteomic biomarkers for diseases, and they can be possibly identified using neuroproteomics. Neuroproteomics is an emerging tool to corroborate disease-associated protein profiles. It also gives an idea about how these proteins interact with other proteins and undergo post-translational modifications. Neuroproteomics is based on bioinformatics, which provides functional characteristics and advances in technology such as mass spectroscopy, and can help in the discovery of various disease-specific biomarkers. This review gives a complete idea about the types of biomarkers, sources of biomarkers, and techniques involved in the discovery of biomarkers for early diagnosis of neurodegenerative diseases.

Effect of fentanyl and its three novel analogues on biochemical, oxidative, histological, and neuroadaptive markers after sub-acute exposure in mice.

AIMS: Comparative sub-acute toxicity, including tolerance and dependence potential of fentanyl and its three novel and potent analogues was determined in mice. MAIN METHODS: Comparative sub-acute (21 d, intraperitoneal; 1/10 LD50) toxicity of fentanyl and its three novel analogues viz., N-(1-(2-phenoxyethyl)-4-piperidinyl) propionanilide (2), N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), and N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6) was determined in mice. Animals were observed for additional seven days to assess the recovery. The brain, liver and kidney toxicity was assessed on the basis of various biochemical, oxidative, histological, and neuroadaptive markers. The expression levels of key neuronal markers associated with drug tolerance and dependence were investigated by western blot and immunohistochemistry. KEY FINDINGS: Fentanyl and its analogues caused abnormal levels of liver and kidney specific biomarkers in plasma. Brain malondialdehyde (MDA) levels were raised by all the treatments and kidney MDA level by analogue 6 (21 d). Reduced glutathione levels in brain, liver, and kidney were diminished by all the treatments (21 & 28 d) and a significant change in the levels of antioxidant enzymes was also produced mainly after 21 d. The deleterious effects of fentanyl and its analogues were further substantiated by corresponding histopathological changes in brain, liver and kidney (21 & 28 d). These compounds were also found to produce neuroadaptive changes as evidenced by the increased expression levels of c-Fos, glucocorticoid receptor, N-methyl-d-aspartate receptor1 and µ-opioid receptor (21 & 28 d). SIGNIFICANCE: Three novel analogues of fentanyl were envisaged to have alternative therapeutic potentials. However, their comparative sub-acute toxicity revealed undesirable side effects, thereby masking their therapeutic ability.

Antimicrobial activity of a novel polyherbal combination for the treatment of vaginal infection.

The present study evaluated the antimicrobial activity of Azadirachta indica (AI), Cichorium intybus (CI), and Trigonella foenum-graecum (TFG) against bacterial and fungal pathogens responsible for the vaginal infections. The AI, CI, and TFG were selected to include antimicrobial and antifungal action against wide range of microbes. The different extracts of the herbs were evaluated for antibacterial and antifungal activity by well diffusion assays. Based on the results, the combination was selected and evaluated, "polyherbal antimicrobial (PHA)." The developed PHA extract demonstrated synergistic broad-spectrum antimicrobial activities including antibacterial and antifungal activity (minimum inhibition concentration: 5-7 mg/ml).

Biochemical, Oxidative, and Physiological Changes Caused by Acute Exposure of Fentanyl and Its 3 Analogs in Rodents.

Synthesis and bioefficacy of fentanyl and its 8 new 1-substituted analogs (1-8) were earlier reported by us. Of these 8 compounds, N-(1-(2-phenoxyethyl)-4-piperidinyl)propionanilide (2), N-isopropyl-3-(4-( N-phenylpropionamido)piperidin-1-yl)propanamide (5), and N- t-butyl-3-(4-( N-phenylpropionamido)piperidin-1-yl) propanamide (6) were found to be more effective and less toxic compared to fentanyl. The present study reports the acute effect of fentanyl (0.50 Median Lethal Dose (LD50); intraperitoneal) and its 3 analogs (2, 5, and 6) on various biochemical and oxidative parameters in mice and various physiological parameters in rats. Blood alkaline phosphatase (1 hour and 7 days) and urea levels (1 hour) were significantly elevated by fentanyl, while alanine aminotransferase levels (1 hour) were increased by both fentanyl and analog 2 compared to the corresponding control. Increase in partial pressure of carbon dioxide and decrease in partial pressure of oxygen were also caused by fentanyl and analog 2 (1 hour). Analog 6 alone elevated malondialdehyde levels in the brain, liver, and kidney tissues (7 days). The LD50 of fentanyl and analogs 2, 5, and 6 were found to be 0.879, 87.88, 69.80, and 55.44 mg/kg, respectively, in rats. Significant decrease in heart rate, mean arterial pressure, respiratory rate (RR), and neuromuscular transmission was produced by fentanyl and analog 2, while analog 5 decreased the RR alone. The changes, particularly the respiratory depression, were found to be reversed by naloxone, a µ-receptor antagonist. Thereby, indicating involvement of µ-receptor mediated effects of the compounds. To conclude, all the analogs were found to be less toxic compared to fentanyl, suggesting their possible role in pain management.

An immunological approach of sperm sexing and different methods for identification of X- and Y-chromosome bearing sperm.

Separation of X- and Y-chromosome bearing sperm has been practiced for selection of desired sex of offspring to increase the profit in livestock industries. At present, fluorescence-activated cell sorter is the only successful method for separation of X- and Y-chromosome bearing sperm. This technology is based on the differences in DNA content between these two types of sperm and has been commercialized for bovine sperm. However, this technology still has problems in terms of high economic cost, sperm damage, and lower pregnancy rates compared to unsorted semen. Therefore, an inexpensive, convenient, and non-invasive approach for sperm sexing would be of benefit to agricultural sector. Within this perspective, immunological sperm sexing method is one of the attractive choices to separate X- and Y-chromosome bearing sperm. This article reviews the current knowledge about immunological approaches, viz., H-Y antigen, sex-specific antigens, and differentially expressed proteins for sperm sexing. Moreover, this review also highlighted the different methods for identification of X- and Y-sperm.

Plasma levels of monokine induced by interferon-gamma/chemokine (C-X-X motif) ligand 9, thymus and activation-regulated chemokine/chemokine (C-C motif) ligand 17 in children with Kawasaki disease.

BACKGROUND: Monokines induced by interferon-gamma/Chemokine (C-X-C motif) ligand 9 (MIG/CXCL9), thymus and activation-regulated chemokine/Chemokine (C-C motif) ligand 17 (TARC/CCL17) are chemotactic factors that specifically collect and activate leukocytes, which are considered as chemoattractants of T helper cells. In the present study, we have investigated the effects of T helper type-1 (Th1) cells and T helper type-2 (Th2) cells in Kawasaki disease (KD) by determining plasma levels of MIG/CXCL9 and TARC/CCL17 and exploring the relationship between MIG/CXCL9, TARC/CCL17 levels and coronary artery lesions (CAL). METHODS: Forty-three children patients with KD and 19 healthy controls were included in this study. General characteristics were obtained from all subjects. Plasma concentrations of chemotactic factors of MIG/CXCL9 and TARC/CCL17 were measured by enzyme-linked immunosorbent assay (ELISA) for all subjects. RESULTS: Plasma levels of MIG/CXCL9, TARC/CCL17, and the ratios of MIG/TARC were significantly elevated in pediatric patients with KD compared to those in the control group. There were also significantly higher levels of MIG/CXCL9, TARC/CCL17, MIG/TARC ratios and prominently lower hemoglobin (Hb) levels in KD with CAL compared to KD without coronary artery lesions (NCAL). Hb was significantly decreased and plasma MIG/CXCL9 levels had a significantly negative correlation with CRP in KD with CAL patients (KD-CAL), whereas a positive correlation of plasma MIG/CXCL 9 with WBC was observed in KD without CAL patients (KD-NCAL). CONCLUSION: Th1 and Th2 cells may be involved in an imbalanced activation in pediatric KD patients during an acute period of the disease. Furthermore, immune lesions of vessels in KD patients may be mediated by the imbalanced activation of Th1 and Th2 cells.

Biochemical, oxidative and histological changes caused by sub-acute oral exposure of some synthetic cyanogens in rats: ameliorative effect of α-ketoglutarate.

Time-dependent cyanide generation and acute toxicity of six different cyanogens were reported earlier, out of which malononitrile (MCN), propionitrile (PCN), and sodium nitroprusside (SNP) were found to be very toxic. We report here 14 d sub-acute toxicity of MCN, PCN, and SNP (oral; 1/10 LD50 daily) in female rats, and its amelioration by α-ketoglutarate (α-KG; oral; 5.26 mmol/kg; +5 min), a potential cyanide antidote. Significant decrease in white blood cells (PCN, SNP), platelets count (PCN), and blood glucose levels (MCN, PCN, SNP) was accompanied by elevated levels of alanine aminotransferase, lactate dehydrogenase (MCN, PCN, SNP), and aspartate aminotransferase (PCN, SNP). Oxidative damage was evidenced by diminished total antioxidant status in plasma and enhanced malondialdehyde levels in liver and kidney. This was accompanied by diminished levels of reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase in the brain, liver and kidney. We also observed increased levels of blood cyanide and thiocyanate, together with inhibition of cytochrome c oxidase and thiosulfate-sulfur transferase activities in total brain and liver homogenate, respectively. Cyanogens also produced several histological changes in all the organs studied. Post-treatment with α-KG significantly abrogated the toxicity of cyanogens, indicating its utility as an antidote for long-term cyanogen exposure.

Accelerated stability and bioassay of a new oral α-ketoglutarate formulation for treating cyanide poisoning.

CONTEXT: Due to several limitations of existing cyanide antidotes, α-ketoglutarate (α-KG) has been proposed as a promising treatment for cyanide. OBJECTIVE: This study reports the accelerated stability and bioassay of a new oral α-KG formulation. MATERIALS AND METHODS: Amber-colored PVDF bottles containing 100 ml of 10% α-KG in 70% sorbitol, preservative (sodium methyl paraben and sodium propyl paraben), sweetener (sodium saccharine), flavor (American ice-cream soda and peppermint) and color (tartrazine), at pH 7.0-8.0 were stored in stability chamber (40 ± 2 °C and 75 ± 5% humidity) for 6 months in a GMP compliant facility. Various physical (pH, color, evaporation, extractable volume and clarity), chemical (identification and quantification of active ingredient) and microbiological (total aerobic count) analyses, together with protection studies were carried periodically in mice. Acute toxicity of the formulation and bioavailability of α-KG were assessed in rats at the beginning of the experiment. RESULTS: No physical changes and microbiological growth were observed in the formulation. After 6 months, α-KG content in the formulation diminished by ∼24% but its protective efficacy against cyanide remained at 5.9-fold. Protection was further characterized spectrophotometrically by disappearance of α-KG spectrum in the presence of cyanide, confirming cyanohydrin formation. Oral LD50 of α-KG formulation in rats was >7.0 g/kg body weight, and did not produce any acute toxicity of clinical significance. Also, an appreciable amount of α-KG was measured in blood. CONCLUSION: As per the guidelines of International Conference on Harmonization, the new α-KG formulation exhibited satisfactory stability, bioefficacy and safety as cyanide antidote.

Synthesis and biological evaluation of some novel 1-substituted fentanyl analogs in Swiss albino mice.

Fentanyl [N-(1-phenethyl-4-piperidinyl)propionanilide] is a potent opioid analgesic agent, but a has narrow therapeutic index. We reported earlier on the synthesis and bioefficacy of fentanyl and its 1-substituted analogs (1-4) in mice. Here we report the synthesis and biological evaluation of four additional analogs, viz. N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6), isopropyl 2-[4-(N-phenylpropionamido)piperidin-1-yl]propionate (7) and t-butyl 2-[4-(N-phenylpropionamido)piperidin-1-yl]propionate (8). The median lethal dose (LD50) determined by intravenous, intraperitoneal and oral routes suggests these analogs to be comparatively less toxic than fentanyl. On the basis of observational assessment on spontaneous activities of the central, peripheral, and autonomic nervous systems, all the analogs were found to be similar to fentanyl. Naloxone hydrochloride abolished the neurotoxic effects of these analogs, thereby ascertaining their opioid receptor-mediated effects. All the analogs displayed significant analgesic effects, measured by formalin-induced hind paw licking and tail immersion tests at their respective median effective dose (ED50). They also exhibited 8-12 fold increase in therapeutic index over fentanyl. However, 5 and 6 alone produced lower ED50 (20.5 and 21.0 µg/kg, respectively) and higher potency ratio (1.37 and 1.33, respectively) compared to fentanyl. They could thus be considered for further studies on pain management.

Genome-wide identification and expression pattern of drought-responsive members of the NAC family in maize.

NAC proteins are plant-specific transcription factors (TFs). Although they play a pivotal role in regulating distinct biological processes, TFs in maize are yet to be investigated comprehensively. Within the maize genome, we identified 152 putative NAC domain-encoding genes (ZmNACs), including eight membrane-bound members, by systematic sequence analysis and physically mapped them onto ten chromosomes of maize. In silico analysis of the ZmNACs and comparison with similar genes in other plants such as Arabidopsis, rice, and soybean, revealed a similar NAC sequence architecture. Phylogenetically, the ZmNACs were arranged into six distinct subgroups (I-VI) possessing conserved motifs. Phylogenetic analysis using stress-related NAC TFs from Arabidopsis, rice, and soybean as seeding sequences identified 24 of the 152 ZmNACs (all from Group II) as putative stress-responsive genes, including one dehydration-responsive ZmSNAC1 gene reported earlier. One drought-tolerant genotype (HKI577) and one susceptible genotype (PC13T-3) were used for studying the expression pattern of the NAC genes during drought stress. qRT-PCR based expression profiles of 11 genes predicted to be related to stress confirmed strong differential gene expression during drought stress. Phylogenetic analyses revealed that ZmNAC18, ZmNAC51, ZmNAC145, and ZmNAC72, which were up-regulated in the tolerant genotype and down-regulated in the susceptible genotype, belonged to the same group to which also belong other drought-responsive genes, namely SNAC1, OsNAC6, ANAC019, and ANAC055, which act as a transcriptional activator and are strongly induced under stress from various abiotic sources. Differentially expressed ZmNAC genes, alone or in combination with each other or with other type(s) of TFs, may control the general cellular machinery and regulate stress-responsive downstream genes. Alternatively, they may serve as a platform to regulate a broad set of genes, which are subsequently fine-tuned by specific regulators. This genome-wide identification and expression profiling opens new avenues for systematic functional analysis of new members of the NAC gene family, which may be exploited in developing lines that are better adapted to drought.

Acute toxicity of some synthetic cyanogens in rats: time-dependent cyanide generation and cytochrome oxidase inhibition in soft tissues after sub-lethal oral intoxication.

Cyanogens include complex nitrile-containing compounds that can generate free cyanide of toxicological significance. Acute toxicity, time-dependent cyanide generation and cytochrome oxidase (CYTOX) inhibition in soft tissues, and urinary thiocyanate levels were measured after acute cyanogen intoxication in rats. Order of cyanogens in terms of LD50 was: malononitrile (MCN)>propionitrile (PCN)≈sodium nitroprusside (SNP)>acrylonitrile (ACN)>succinonitrile (SCN)>acetonitrile (ATCN) for oral, and SNP>MCN>ACN>PCN>SCN>ATCN for intraperitoneal and subcutaneous routes. MCN was most toxic by oral (LD50=66.4 mg/kg) and SNP by intraperitoneal (LD50=16.7 mg/kg) and subcutaneous (LD50=11.9 mg/kg) routes. Minimum survival time (25 min) was recorded after 4.0 LD50 ATCN. Order of cyanogens (0.75 LD50; oral) on the basis of maximum blood cyanide and time of peak cyanide generation were: ATCN>SNP>SCN>PCN>MCN>ACN, and MCN (30 min)

Development of controlled release formulations of thiram employing amphiphilic polymers and their bioefficacy evaluation in seed quality enhancement studies.

Controlled release formulations of Thiram (Dimethylcarbamothioylsulfanyl-N,N-dimethylcarbamodithioate), a contact fungicide, have been prepared using laboratory synthesized poly(ethylene glycol) (PEG) based functionalized amphiphilic copolymers. The kinetics of thiram from developed controlled release (CR) formulations were studied in comparison with that of the commercially available 75 WS. Release from the commercial formulation was faster than with the developed CR formulations. Maximum amount of thiram was released on 35th day for PEG-2000 4d, 28th day for PEG-1500 4c, 21st day for PEG-1000 4b and 15th day for PEG-600 4a in comparison to commercial formulation (7th day). The diffusion exponent (n) of thiram in water ranged from 0.356 to 0.545 in the tested formulations. The half-release (t(1/2)) values ranged between 14.78 to 22.1 days, and the Period of Optimum Availability (POA) of thiram ranged from 7.79 to 25.15 days. An effort has also been made to identify the suitable polymers that could reduce the seed deterioration during storage and also act as an effective carrier of fungicide thiram. The results demonstrate that the seeds coated with the different formulations deteriorated at a slower pace as manifested in high germination percentage over control. Apart from the fungicidal effect of thiram, the polymers acted as barriers to moisture reducing the rate of seed deterioration and checked the degradation of thiram. The CR formulation 4d, with PEG 2000, was found to be most effective as seed coat.

Fast disintegrating tablets: Opportunity in drug delivery system.

Fast disintegrating tablets (FDTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Oral drug delivery remains the preferred route for administration of various drugs. Recent developments in the technology have prompted scientists to develop FDTs with improved patient compliance and convenience. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. The popularity and usefulness of the formulation resulted in development of several FDT technologies. FDTs are solid unit dosage forms, which disintegrate or dissolve rapidly in the mouth without chewing and water. FDTs or orally disintegrating tablets provide an advantage particularly for pediatric and geriatric populations who have difficulty in swallowing conventional tablets and capsules. This review describes various formulations and technologies developed to achieve fast dissolution/dispersion of tablets in the oral cavity. In particular, this review describes in detail FDT technologies based on lyophilization, molding, sublimation, and compaction, as well as approaches to enhancing the FDT properties, such as spray drying and use of disintegrants. In addition, taste-masking technologies, experimental measurements of disintegration times, and dissolution are also discussed.