Mechanisms of medicinal, pharmaceutical, and immunomodulatory action of probiotics bacteria and their secondary metabolites against disease management: an overview.

Probiotics or bacteriotherapy is today's hot issue for public entities (Food and Agriculture Organization, and World Health Organization) as well as health and food industries since Metchnikoff and his colleagues hypothesized the correlation between probiotic consumption and human's health. They contribute to the newest and highly efficient arena of promising biotherapeutics. These are usually attractive in biomedical applications such as gut-related diseases like irritable bowel disease, diarrhea, gastrointestinal disorders, fungal infections, various allergies, parasitic and bacterial infections, viral diseases, and intestinal inflammation, and are also worth immunomodulation. The useful impact of probiotics is not limited to gut-related diseases alone. Still, these have proven benefits in various acute and chronic infectious diseases, like cancer, human immunodeficiency virus (HIV) diseases, and high serum cholesterol. Recently, different researchers have paid special attention to investigating biomedical applications of probiotics, but consolidated data regarding bacteriotherapy with a detailed mechanistically applied approach is scarce and controversial. The present article reviews the bio-interface of probiotic strains, mainly (i) why the demand for probiotics?, (ii) the current status of probiotics, (iii) an alternative to antibiotics, (iv) the potential applications towards disease management, (v) probiotics and industrialization, and (vi) futuristic approach.

Green synthesised AuNps using Ajuga Bracteosa extract and AuNps-Free supernatant exhibited equivalent antibacterial and anticancerous efficacies.

The current study is designed to synthesize gold nanoparticles using Ajuga bracteosa extract, which is a highly known medicinal herb found in the northern Himalayas. The synthesized gold nanoparticles were initially characterized by UV-Vis spectrophotometer, SEM, FTIR, pXRD, and, GC-MS. Antibacterial efficacy of A. bracteosa extract, AuNps, and AuNps-free supernatant activity was checked against highly pathogenic clinical isolates of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa via agar well diffusion method, assuming that supernatant might have active compounds. The Nps-free supernatant showed the maximum antibacterial activity against E. coli (20.8±0.3 mm), Staphylococcus aureus (16.5±0.5), and Pseudomonas aeruginosa (13±0.6). While green synthesized AuNps showed effective antibacterial activity (Escherichia coli (16.4±0.3mm), Staphylococcus aureus (15.05±0.5mm), and Pseudomonas aeruginosa (11.07±0.6mm)) which was high compared to A. bracteosa extract. Anticancer activity was assessed by MTT assay on U87 and HEK293 cell lines. Aj-AuNps have an antigrowth effect on both the cell lines however Aj-AuNps-free supernatant which was also evaluated along with the Aj-AuNps, showed high toxicity toward HEK293 cell line compared to U87. Further, the GC-MS analysis of supernatant showed the presence of resultant toxic compounds after the reduction of gold salt, which include Trichloromethane, Propanoic acid, 2-methyl-, methyl ester, Methyl isovalerate, Pentanoic acid, 2-hydroxy-4-methyl-, Benzene-propanoic acid, and alpha-hydroxy. Based on the observation small molecular weight ligands of Ajuga bracteosa were analyzed in-silico for their binding efficacy towards selected membrane proteins of our target pathogens. RMSD is also calculated for the best docked protein ligand pose. The results revealed that among all listed ligands, Ergosterol and Decacetylajugrin IV have high virtuous binding affinities towards the membrane proteins of targeted pathogens. The current findings revealed that the Aj-AuNps are good antibacterial as well as anticancerous agents while the Nps-free supernatant is also exceedingly effective against resistant pathogens and cancer cell lines.

Acute toxicity, anti-diabetic, and anti-cancerous potential of Trillium govanianum-conjugated silver nanoparticles in Balb/c mice.

BACKGROUND: The current study aimed to develop an economic plant-based therapeutic agent to improve the treatment strategies for diseases at the nano-scale because Cancer and Diabetes mellitus are major concerns in developing countries. Therefore, in vitro and in vivo anti-diabetic and anti-cancerous activities of Trillium govanianum conjugated silver nanoparticles were assessed. METHODS: In the current study synthesis of silver nanoparticles using Trillium govanianum and characterization were done using a scanning electron microscope, UV-visible spectrophotometer, and FTIR analysis. The in vitro and in vivo anti-diabetic and anti-cancerous potential (200 mg/kg and 400 mg/kg) were carried out. RESULTS: It was discovered that Balb/c mice did not show any major alterations during observation of acute oral toxicity when administered orally both TGaqu (1000 mg/kg) and TGAgNPs (1000 mg/kg), and results revealed that 1000 mg/kg is not lethal dose as did not find any abnormalities in epidermal and dermal layers when exposed to TGAgNPs. In vitro studies showed that TGAgNPs could not only inhibit alpha-glucosidase and protein kinases but were also potent against the brine shrimp. Though, a significant reduction in blood glucose levels and significant anti-cancerous effects was recorded when alloxan-treated and CCl4-induced mice were treated with TGAgNPs and TGaqu. CONCLUSION: Both in vivo and in vitro studies revealed that TGaqu and TGAgNPs are not toxic at 200 mg/kg, 400 mg/kg, and 1000 mg/kg doses and possess strong anti-diabetic and anti-cancerous effects due to the presence of phyto-constituents. Further, suggesting that green synthesized silver nanoparticles could be used in pharmaceutical industries to develop potent therapeutic agents.

Interactions of Chitosan-coated Green Synthesized Silver Nanoparticles using Mentha spicata and Standard Antibiotics against Bacterial Pathogens.

BACKGROUND: Infectious diseases are caused by various multidrug-resistant pathogenic bacteria and in recent scenarios, nanoparticles have been used as innovative antimicrobial agents. AIMS: This current research aimed to evaluate the bactericidal effect of chitosan-coated green synthesized silver nanoparticles using aqueous extract of Mentha spicata (MSaqu) against bacterial pathogens, i.e., Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, and Streptococcus pyogenes. METHODS: Synthesis and characterization of silver nanoparticles (MSAgNPs) were carried out via atomic absorption spectrometer and Fourier-transform infrared spectroscopy. Agar well and agar disc diffusion methods were used to assess the antibacterial and synergistic effect of chitosanmediated biogenic silver nanoparticles and standard antibiotics. Three types of interactions, i.e., antagonistic (↓), synergistic (↑), and additive (¥) were observed. RESULTS: Synergistic effect was recorded against Pseudomonas aeruginosa (8.5±0.25 mm↑), Serratia marcescens (19.0±1.0 mm↑), and Klebsiela pneumonia (8.5±0.25 mm↑), an additive effect was exhibited by Escherichia coli (9.0±0.0 mm¥), Streptococcus pyogenes (10.0±0.0 mm¥), and Staphylococcus aureus (7.5±0.25 mm↓) and they showed antagonistic effects when chitosan-coated silver nanoparticles (CLMSAgNPs) were applied compared to chitosan, MSaqu, and MSAgNPs. Interesting antibacterial results were recorded when chitosan-coated Mentha spicata extract and silver nanoparticles were applied along with antibiotics. The synergistic effects of chitosan-coated silver nanoparticles (CLMSAgNPs) + K were recorded against E. coli (14.5±0.25 mm). The synergistic effects of chitosan-coated silver nanoparticles (CLMSAgNPs) + AML were recorded against E. coli (5.5±0.0 mm), S. pyogenes (10.0±0.0 mm), K. pneumonia (5.5±0.0 mm), and S. aureus (4.0±0.0 mm). The synergistic effects of chitosan-coated silver nanoparticles (CLMSAgNPs) + NOR were recorded against E. coli (16.0±0.0 mm), P. aeruginosa (19.0±0.0 mm), S. marcescens (19.5±0.25 mm), S. pyogenes (11.5.0±0.25 mm), K. pneumonia (23.0±0.0 mm), and S. aureus (8.5±0.25 mm). CONCLUSION: Current findings concluded that chitosan-coated biogenic silver nanoparticles have potential bactericidal effects against infectious pathogens and could be used as forthcoming antibacterial agents.

COYOTE: Sequence-derived structural descriptors-based computational identification of glycoproteins.

Glycoproteins play an important and ubiquitous role in many biological processes such as protein folding, cell-to-cell signaling, invading microorganism infection, tumor metastasis, and leukocyte trafficking. The key mechanism of glycoproteins must be revealed to model and refine glycosylated protein recognition, which will eventually assist in the design and discovery of carbohydrate-derived therapeutics. Experimental procedures involving wet-lab experiments to reveal glycoproteins are very time-consuming, laborious, and highly costly. However, costly and tedious experimental procedures can be assisted by ranking the most probable glycoproteins through computational methods with improved accuracy. In this study, we have proposed a novel machine learning-based predictive model for glycoproteins identification. Our proposed model is based on sequence-derived structural descriptors (SDSD) that fill the gap of unavailability of protein 3D structures and lack of accuracy in sequence information alone. Through a series of simulation studies, we have shown that our proposed model gives state-of-the-art generalization performance verified through various machine learning-centric and biologically relevant techniques and metrics. Through data mining in this study, we have also identified the role of descriptors in determining glycoproteins. Python-based standalone code together with a webserver implementation of our proposed model (COYOTE: identifiCation Of glYcoprOteins Through sEquences) is available at the URL: https://sites.google.com/view/wajidarshad/software.

In vitro Antimicrobial Activity of Biogenically Synthesized Nickel and Zinc Nanoparticles against Selected Pathogenic Bacterial Strains.

Bacterial resistance to already present antibiotics demands for new approaches in field of medicine. Scientists prefer nanoparticles (NPs) due to their promising potential in many applications. Two bacterial strains, Escherichia coli and Bacillus subtilis were used for biogenic synthesis of NPs. Characterization of prepared NPs was accomplished using UV-vis spectroscopy and fourier transform infrared spectroscopy (FTIR). The prepared NPs were confirmed by the color change from pale yellow to having white deposition for Zn NPs while from dark green to light green for Ni NPs. UV-vis spectroscopy of E. coli and B. subtilis based ZnNPs showed highest peak at 354nm and 362nm, respectively. Likewise, E. coli and B. subtilis NiNPs showed peaks at 246 nm and 238 nm, respectively. Antibacterial activity of B. subtilis based ZnNPs showed significant (p ≤ 0.05) zone of inhibition (ZOI; 27.3±0.6) against B. subtilis and 26.66±0.67 against E. coli at 100 mg/mL. Antibacterial activity of E. coli based ZnNPs showed 8.3±0.3 ZOI against B. subtilis and 6.6±0.3 ZOI against E. coli while NiNPs showed (25.0±0.0 mm) (ZOI) against B. subtilis and (25.0 ± 0.3 mm) against E. coli. Minimum inhibitory concentration (MIC) of E. coli ZnNPs showed values of 6.7±0.3 µg/mL for E. coli and 4.7±0.3 µg/mL for B. subtilis. MIC of B. subtilis ZnNPs showed 5.3±0.3 µg/mL for E. coli and 6.6±0.3 µg/mL for B. subtilis while NiNPs showed 33.0±1.0 µg/mL against E. coli and 24.0±1.0 µg/mL against B. subtilis as effective inhibitory concentrations. Minimum bactericidal concentration (MBC) of E. coli ZnNPs showed 7.3±0.3 µg/mL for E. coli and 8.3±0.3 µg/mL for B. subtilis. MBC of B. subtilis ZnNPs showed 7.6±0.3 µg/mL for E. coli and 8.6±0.3 µg/mL for B. subtilis while NiNPs showed 45.7±1.3 µg/mL against E. coli and 33.0±1.0 µg/mL against B. subtilis as effective inhibitory concentrations. It was concluded from the current study that biogenically synthesized ZnNPs and NiNPs are effective as promising antibacterial agents and have potential applications in biomedical fields.

SIP: A computational prediction of S-Adenosyl methionine (SAM) interacting proteins and their interaction sites through primary structures.

S-Adenosyl methionine (SAM), a universal methyl group donor, plays a vital role in biosynthesis and acts as an inhibitor to many enzymes. Due to protein interaction-dependent biological role, SAM has become a favorite target in various therapeutical and clinical studies such as treating cancer, Alzheimer's, epilepsy, and neurological disorders. Therefore, the identification of the SAM interacting proteins and their interaction sites is a biologically significant problem. However, wet-lab techniques, though accurate, to identify SAM interactions and interaction sites are tedious and costly. Therefore, efficient and accurate computational methods for this purpose are vital to the design and assist such wet-lab experiments. In this study, we present machine learning-based models to predict SAM interacting proteins and their interaction sites by using only primary structures of proteins. Here we modeled SAM interaction prediction through whole protein sequence features along with different classifiers. Whereas, we modeled SAM interaction site prediction through overlapping sequence windows and ranking with multiple instance learning that allows handling imprecisely annotated SAM interaction sites. Through a series of simulation studies along with biological significant evaluation, we showed that our proposed models give a state-of-the-art performance for both SAM interaction and interaction site prediction. Through data mining in this study, we have also identified various characteristics of amino acid sub-sequences and their relative position to effectively locate interaction sites in a SAM interacting protein. Python code for training and evaluating our proposed models together with a webserver implementation as SIP (Sam Interaction Predictor) is available at the URL: https://sites.google.com/view/wajidarshad/software.

Cytotoxicity, Anti-diabetic, and Hepato-protective Potential of Ajuga bracteosa-conjugated Silver Nanoparticles in Balb/c Mice.

BACKGROUND: Ajuga bracteosa is a traditional herb used against various diseases. OBJECTIVES: Current research aimed to investigate the anti-diabetic and hepato-protective effect of green synthesized silver nanoparticles (ABAgNPs) using Ajuga bracteosa aqueous extract (ABaqu). METHODS: In vitro anti-diabetic and cytotoxic effects were carried out via α- glucosidase inhibition, brine shrimp lethality, and protein kinase inhibition assays. For in vivo screening of 200 mg/kg and 400 mg/kg of both ABAgNPs and ABaqu in alloxan-induced and CCl4-induced Swiss albino mice were used. Liver and kidney functional markers, hematology, and histopathological studies were carried out after 14 days of administration. RESULTS: In vivo antidiabetic and anti-cancerous effects showed valuable anti-hyperglycemic and hepatoprotective potential when mice were treated with ABaqu and ABAgNPs. A significant reduction in the blood glucose level was recorded when ABaqu and ABAgNPs were administrated orally compared to Glibenclamide treated group. Significant reduction in ALT, AST, ALP, urea, uric acid, and creatinine was recorded in ABaqu and ABAgNPs treated diabetic mice. The hepato-protective findings indicated that ALT, ALP, AST were elevated in CCl4-induced mice while declined in both ABAgNPs and ABaqu treated CCl4-induced mice. Histopathological examination revealed that ABAgNPs have hepato-protective activity. CONCLUSION: It was concluded that ABAgNPs and ABaqu possessed strong anti-diabetic and hepatoprotective phytoconstituents, which could be used in the prevention of diseases.

Retracted: Partial purification and characterization of lipase from locally produced edible oil-seeds and its relevance in industries.

Lipase was extracted from germinating seeds of Helianthus annus (Sunflower), Zea mays (Maize), and Brassica compastris (Mustard). The lipolytic activity was assessed using olive oil as substrate at different germination-time and the maximum-activity was obtained after 120 hr. Partial-purification was executed by precipitating the seed-homogenate with varying concentration of ammonium sulfate solution. 80% ammonium sulfate solution showed maximum lipase activity of 5320IUml-1 , 3500IUml-1 , 3080IUml-1 with 9.6, 6.9, and 4.8-fold purification and total protein content of 162, 84, and 60 mg for partially purified enzyme extracts namely SN5, BN5, and MN5, respectively. The optimum temperature and pH observed for hydrolysis of olive oil were 37°C, and 8.0 respectively. Enzyme was found to be stable upto 6 days at 4°C and its activity was stimulated by Ca+2 ions. Oil-stains removal from cotton fabric was observed to be superior in the presence of lipase and detergent. Moreover, the SN5, BN5, and MN5 lipase increased free fatty acid release upto 4.2, 4.3, and 3.8 mg, respectively than wastewater without treatment of lipase (0.21 mg) and promoted fat hydrolysis to approximately 40, 42, and 48% mass reduction after 6 hr incubation of fat particle at a concentration of 20 mg/ml. Biodiesel produced by catalyzing transesterification of vegetable oil with SN5, BN5, and MN5 lipase provided an acid value of 0.8, 1.08, and 0.5 mg/g, viscosity 5.50, 5.7, and 5.53 mm2 /s and density 0.87, 0.88, and 0.79 g/ml, respectively. To the best of our knowledge, no such study has been conducted prior on lipase from the seeds mentioned above in Azad Kashmir region.

Evaluation of Cadmium Chloride-Induced Toxicity in Chicks Via Hematological, Biochemical Parameters, and Cadmium Level in Tissues.

Cadmium is a heavy metal and a non-biodegradable environmental contaminant, and its omnipresence ensures its recurrent exposure to humans and animals. Its intake by chicks leads to fatal implications. Cadmium chloride (CdCl2) because of its bio-accumulative nature is an emerging threat to the poultry industry as well as to the humans which consumes these cadmium-intoxicated chickens. In the current study, the target was to elucidate the toxic effects of CdCl2on body weight, hematological, and biochemical parameters as well as its bioaccumulation in different organs of broiler chicks. Various concentrations of CdCl2 (0, 12, 24, 38, and 48 mg/kg body weight) were administered orally to five groups (A, B, C, D, and E) of broiler chicks, respectively. The biometric screening of the exposed birds was carried out by hematological parameters such as packed cell volume (PCV), total erythrocyte count (TEC), mean corpuscular hemoglobin concentration (MCHC), total protein, white blood cells (WBC), and hemoglobin (Hb), as well as biochemical parameters superoxide dismutase (SOD), low-density lipoprotein (LDL), glutathione peroxidase (GPx), and high-density lipoprotein (HDL) with commercially available kits. Metal accumulation in different organs was detected using atomic absorption spectrophotometer. The compound exposure produced a varied impact on broiler birds. Hematological parameters showed a significant decrease except for WBC. Biochemical parameters also decreased significantly in a dose-dependent manner. However, it was revealed that the body weight of chickens was not affected considerably after CdCl2 exposure. A direct relationship was detected between the accumulation of metal within tissues (lungs, heart, and flesh) and exposure frequency. It can be deduced that an increase in Cd deposition in tissues may lead to an alteration in hematological-biochemical markers which may significantly contribute to systemic toxicity in broilers.

Spectroscopic characterizations, structural peculiarities, molecular docking study and evaluation of biological potential of newly designed organotin(IV) carboxylates.

In the search for new therapeutic agents we have synthesized 13 new organotin(IV) carboxylate derivatives of (E)-4-((4-methoxy-2-nitrophenyl)amino)-4-oxobut-2-enoic acid. The synthesized complexes were characterized by several spectroscopic techniques. A chelating or bridging bidentate nature of the carboxylate ligand was suggested from the solid state FT-IR results. Solution state multinuclear NMR (1H, 13C and 119Sn) results reveal that the geometry around the Sn atom in triorganotin(IV) complexes is trigonal bipyramidal and in diorganotin(IV) complexes is octahedral. The ligand, (E)-4-((4-methoxy-2-nitrophenyl)amino)-4-oxobut-2-enoic acid, complex 1 and complex 2 were also analyzed by single crystal X-ray technique and the results fully supports the spectroscopic data. For 1 and 2 the geometry optimized by the single crystal X-ray analyses is distorted trigonal bipyramidal. The interaction of the studied compounds with SS-DNA was investigated by UV-Vis. Spectroscopy and Molecular docking showing an intercalative mode of binding. The evaluation of the screened compounds for cancer treatment displays even higher than that of the vincristine used as a standard drug. Similarly the performance of the tested compounds as an antileishmanial agent considers them very close in activity to the standard drug, amphotericin B. The antibacterial results show that the most of the compounds have a moderate sensitivity against the studied bacterial pathogens.

Toxicological effects of toxic metals (cadmium and mercury) on blood and the thyroid gland and pharmacological intervention by vitamin C in rabbits.

Cadmium and mercury are non-biodegradable toxic metals that may cause many detrimental effects to the thyroid gland and blood. Vitamin C has been found to be a significant chain-breaking antioxidant and enzyme co-factor against metal toxicity and thus make them less available for animals. The current study was performed to find the effect of individual metals (cadmium and mercury), their co-administration, and the ameliorative effects of vitamin C on some of the parameters that indicate oxidative stress and thyroid dysfunction. Cadmium chloride (1.5 mg/kg), mercuric chloride (1.2 mg/kg), and vitamin C (150 mg/kg of body weight) were orally administered to eight treatment groups of the rabbits (1. control; 2. Vit C; 3. CdCl2; 4. HgCl2; 5. Vit C + CdCl2; 6. Vit C + HgCl2; 7. CdCl2 + HgCl2, and 8. Vit C + CdCl2 + HgCl2). After the biometric measurements of all experimental rabbits, biochemical parameters viz. triidothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), and triglycerides were measured using commercially available kits. The results exhibited significant decline (p < 0.05) in mean hemoglobin, corpuscular hemoglobin, packed cell volume, T3 (0.4 ± 0.0 ng/ml), and T4 (26.3 ± 1.6 ng/ml) concentration. While, TSH (0.23 ± 0.01 nmol/l) and triglyceride (4.42 ± 0.18 nmol/l) were significantly (p < 0.05) increased but chemo-treatment with Vit C reduces the effects of Cd, Hg, and their co-administration but not regained the values similar to those of controls. This indicates that Vit C had a shielding effect on the possible metal toxicity. The Cd and Hg also found to accumulate in vital organs when measured by atomic absorption spectrophotometer. The metal concentration trend was observed as follows: kidney > liver > heart > lungs. It was concluded that Cd and Hg are toxic and tended to bioaccumulate in different organs and their toxic action can be subdued by vitamin C in biological systems.

The protective role of ascorbic acid in the hepatotoxicity of cadmium and mercury in rabbits.

The liver is one of the vital and sensitive organs which are usually exposed against the toxicity of mercury (Hg) and cadmium (Cd). The main objective of the current study was to evaluate the potential toxicological effects of both Cd and Hg as individual and combined. Hepatotoxicity was evaluated by monitoring the biochemical parameters of the liver and their accumulation in the liver as well as therapeutic role of vitamin C in said toxicity in rabbits (Oryctolagus cuniculus). In this research, cadmium chloride (1.5 mg/kg), mercuric chloride (1.2 mg/kg), and vitamin C (150 mg/kg of body weight) were orally administered to treatment groups of the rabbits for 28 alternative days. Various biochemical parameters of the liver such as lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT), bilirubin, alanine aminotransferase (ALAT), total protein, and gamma glutamyl transferase (GGT) were estimated using blood samples. Some biochemical parameters like ASAT, ALAT, LDH, GGT, and bilirubin were significantly elevated (P ≤ 0.001) in individual Cd and Hg treatment groups, while the level of total protein was found to be significantly declined. The effects of Cd and Hg in the presence of vitamin C on these biochemical parameters were low as compared to metals-treated groups. Similar results were found when rabbits were treated with co-administration of both metals and vitamin C. Accumulation of Cd and Hg found to be higher in the liver. However, chemoprevention and chemotreatment with vitamin C significantly (P ≤ 0.01) minimized the toxicological effects of both metals but not regained the accumulation similar to that of the control group. The findings of this study provide awareness on accumulation of metals in the liver in rabbits and their toxicity tested through biochemical parameters as well as the therapeutic role of vitamin C in such alterations.

Renal toxicity of heavy metals (cadmium and mercury) and their amelioration with ascorbic acid in rabbits.

Cadmium and mercury are among the most toxic and dangerous environmental pollutants that may cause fatal implications. Vitamin C is an important chain-breaking antioxidant and enzyme co-factor against heavy metals. The objective of the present study was to evaluate the toxicological effects of cadmium chloride, mercuric chloride, and their co-administration on biochemical parameters of blood serum and metal bioaccumulation in kidneys and also to elucidate the protective effect of vitamin C in rabbits against these metals. In the current research, cadmium chloride (1.5 mg/kg), mercuric chloride(1.2 mg/kg), and vitamin C (150 mg/kg of body weight) were orally administered to eight treatment groups of the rabbits (1, control; 2, vitamin; 3, CdCl2; 4, HgCl2; 5, vitamin + CdCl2; 6, vitamin + HgCl2; 7, CdCl2 + HgCl2, and 8, vitamin + CdCl2 + HgCl2). After the biometric measurements of all experimental rabbits, biochemical parameters viz. creatinine, cystatin C, uric acid, and alkaline phosphatase (ALP) and metal bioaccumulation were determined using commercially available kits and atomic absorption spectrophotometer, respectively. The levels of creatinine (28.3 ± 1.1 µmol/l), cystatin C (1932.5 ± 38.5 ηg/ml), uric acid (4.8 ± 0.1 mg/day), and ALP (51.6 ± 1.1 IU/l) were significantly (P < 0.05) increased due to administration of mercuric chloride but in the presence of vitamin C, the effects of mercuric chloride on creatinine (21.9 ± 1.4 µmol/l), cystatin C (1676.2 ± 42.2 ηg/ml), uric acid (3.9 ± 0.1 mg/day), and ALP (43.3 ± 0.8 IU/l) were less as compared to metal-exposed specimens. Similar results were found in rabbits treated with cadmium chloride and vitamin C and also with co-administration of both metals and vitamin C. Because of the bio-accumulative nature of cadmium chloride and mercuric chloride, these metals were accumulated in kidneys of rabbits, which might lead to deleterious effects. The results of the present study provide an insight into the toxicity of the cadmium chloride, mercuric chloride, and/or their combination on biochemical parameters as well as kidneys of the rabbits and the ameliorating potential of vitamin C against these metals is also evaluated.

Biological Activities and Secondary Metabolite Screening of Rumex hastatus Extract through Fourier Transform Infrared and Raman Spectroscopy.

BACKGROUND: Human infectious diseases are caused by various pathogens including bacteria, fungi, viruses, parasites, and protozoans. These infectious agents are controlled by using synthetic drugs as well as natural sources. OBJECTIVE: The aim of current study was to evaluate the antibacterial effect of Rumex hastatus against clinical bacterial pathogens. METHODS: In current research antibacterial effect of Rumex hastatus was analyzed against seven clinical pathogenic bacteria such as Escherichia coli, Serratia marcescens, Streptococcus pyogenes, Staphylococcus epidermidis, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa through agar well diffusion method. The boiled extract was used for the phytochemical screening, antioxidant potential, thin layer chromatography, bio-autography, and spot screening. Genomic DNA was extracted to find the DNA protection effect of R. hastatus. RESULTS: Antibacterial results showed that diethyl ether extract has the maximum inhibition of S. pyogenes (9.66 ± 0.57 mm). Acetone and diethyl ether extracts showed moderate inhibition of K. pneumoniae (6.33 ± 1.52 mm and 5.66 ±1.15 mm) and S. aureus (6.33 ± 1.52 mm and 5.66 ± 0.57 mm). Similarly, chloroform extract indicated moderate inhibition of S. pyogenes (5.66 ± 1.15 mm). Ethanol extract had low or even no effect on the growth of bacteria. Genomic DNA extraction also encouraged the antibacterial effect of R. hastatus. Various phytochemical constituents such as ketoses, oligosaccharides, amino acids, amines, sugars, flavonoids, and antioxidant constituents were detected. TLC-Bioautography and spot screening results revealed the potential use of R. hustatus as an antibacterial agent. CONCLUSION: It was concluded that most of the tested fractions appeared as an important source for the discovery of new antimicrobial drugs.

Phytochemical Screening, Alpha-Glucosidase Inhibition, Antibacterial and Antioxidant Potential of Ajuga bracteosa Extracts.

BACKGROUND: Ajuga bracteosa, a medicinal herb, is used by local community to cure a number of diseases such as inflammation, jaundice bronchial asthma, cancer and diabetes. OBJECTIVES: The aim of present work was to evaluate the antioxidant potential, in vitro antidiabetic and antimicrobial effects of A. bracteosa. METHODS: n-hexane, ethyl acetate, chloroform, acetone, methanol and aqueous extracts of Ajuga bracteosa roots, were prepared via maceration. Antibacterial activity was carried out by agar well diffusion method. Quantitative and qualitative phytochemical screening was done. The antioxidant activity was determined by iron (II) chelating activity, iron reducing power, DPPH, and ABTS free radical scavenging methods, Antidiabetic activity was evaluated through inhibition of α-glucosidase assay. RESULTS: Phytochemical analysis showed the presence of phenols, flavonoids, tannins, saponins, quinines, terpenoids, xanthoproteins, glycosides, carbohydrates, steroids, phytosterols and amino acids. DPPH and ABTS potential values were recorded as 61.92% to 88.84% and 0.11% to 38.82%, respectively. Total phenolic and total flavonoid contents were expressed as gallic acid and rutin equivalents. Total iron content was expressed as FeSO4 equivalents. Chloroform and n-hexane extracts showed significant enzyme inhibition potential with IC50 values of 29.92 µg/ml and 131.7 µg/ml respectively. Aqueous extract showed maximum inhibition of E. coli, S. typhimurium, E. amnigenus, S. pyogenes, and S. aureus, (18.0±1.0 mm, 12.5±0.7 mm, 17.0±0.0 mm, 11.0±0.0 mm and 15.3±2.0 mm mm), respectively. Similarly, n-hexane extract showed maximum inhibition of E. coli, E. amnigenus, S. aureus (11.6±1.5 mm; 11.3±1.5 mm; 13.3±0.5 mm). This study also shows that n-hexane, chloroform, ethyl acetate and aqueous extracts of A. bracteosa root possess α-glucosidase inhibitory activities and therefore it may be used as hypoglycemic agents in the management of postprandial hyperglycemia. CONCLUSION: Ajuga bracteosa root extracts may provide a basis for development of antioxidant, antimicrobial and antidiabetic drugs.

Transient expression of ßC1 protein differentially regulates host genes related to stress response, chloroplast and mitochondrial functions.

BACKGROUND: Geminiviruses are emerging plant pathogens that infect a wide variety of crops including cotton, cassava, vegetables, ornamental plants and cereals. The geminivirus disease complex consists of monopartite begomoviruses that require betasatellites for the expression of disease symptoms. These complexes are widespread throughout the Old World and cause economically important diseases on several crops. A single protein encoded by betasatellites, termed ßC1, is a suppressor of gene silencing, inducer of disease symptoms and is possibly involved in virus movement. Studies of the interaction of ßC1 with hosts can provide useful insight into virus-host interactions and aid in the development of novel control strategies. We have used the differential display technique to isolate host genes which are differentially regulated upon transient expression of the ßC1 protein of chili leaf curl betasatellite (ChLCB) in Nicotiana tabacum. RESULTS: Through differential display analysis, eight genes were isolated from Nicotiana tabacum, at two and four days after infiltration with ßC1 of ChLCB, expressed under the control of the Cauliflower mosaic virus 35S promoter. Cloning and sequence analysis of differentially amplified products suggested that these genes were involved in ATP synthesis, and acted as electron carriers for respiration and photosynthesis processes. These differentially expressed genes (DEGs) play an important role in plant growth and development, cell protection, defence processes, replication mechanisms and detoxification responses. Kegg orthology based annotation system analysis of these DEGs demonstrated that one of the genes, coding for polynucleotide nucleotidyl transferase, is involved in purine and pyrimidine metabolic pathways and is an RNA binding protein which is involved in RNA degradation. CONCLUSION: ßC1 differentially regulated genes are mostly involved in chloroplast and mitochondrial functions. ßC1 also increases the expression of those genes which are involved in purine and pyrimidine metabolism. This information gives a new insight into the interaction of ßC1 with the host and can be used to understand host-virus interactions in follow-up studies.