At present metformin is the core for the management of type-2 diabetes mellitus. The key clue of metformin as a hypoglycemic drug was collected from the traditional utilization of Galega officinalis for the management of diabetes. Modern study recommends several valuable activities of Metformin other than the hypoglycemic effect such as type-1 diabetes mellitus, polycystic ovary syndrome, cholesterol-lowering effect, avoidance of heart disease, age, cancer, and neuroprotection. In the present review, we are discussing about the source and versatile utilization of metformin and its outcome.

Background and objective Zingiber officinaleis, known as ginger, has been used in Arabic traditional medicine for its immense pharmacological effects. Encapsulation of the bioactive compounds is a powerful approach to improve their bioactivities, decrease their toxicities, and expand their physical steadiness. In this investigation, the cytotoxic activity of free and nanoencapsulated ginger against three human tumor cell lines was assessed with respect to IC50 and selectivity index. Additionally, the prompted apoptotic changes by free and nanoencapsulated ginger were evaluated. Materials and methods Ethanol extract was prepared from powdered ginger. Total phenol content was measured using the Folin–Ciocalteau method, where ginger extract (GE) (30 µl) was mixed with 2.37 ml deionized water, and then 150 µl Folin–Ciocalteau’s phenol reagent and 450 µl sodium bicarbonate (20% w/v) were added to the mixture. Absorbance was measured at 760 nm. Preparations of GE-loaded in Whey protein isolate (WPI) were done through charged alkaline WPI solution by absolute ethanol. Results GE demonstrated the most powerful anticancer activity on breast cancer cells with high selectivity index (SI) and specificity. The particle size of WPI nanoparticles was 91.98 nm, which decreased by increasing the loading percentage of the ginger-extract reaching 73.47 nm with maximum loading. Conversely, the encapsulation efficiency (EE) of the encapsulated ginger-extract in WPI nanoparticles was 79.78%, which was increased by increasing the loading percentage of the ginger extract. Moreover, nanoparticle yield was higher than 78.45% for all samples. Encapsulation of GE enhanced the tumor suppression effect of the free GE. This may be attributed to the slow release and high solubility of the nanoencapsulated ginger. Conclusion Nanoencapsulation using WPI upgraded altogether the bioavailability of ginger and its anticancer action in comparison with free GE.

Background and objectives The conservation and management of threatened and endangered species is a tremendous challenge that must be addressed to achieve the goal of halting the loss of plant biodiversity. According to the IUCN Red List of Threatened Species, Cyperus esculentus lies in the least concern category. This means that it has been evaluated against the Red List criteria and does not qualify for critically endangered, vulnerable, or near threatened. In Egypt, the people depend mainly on the wild growing tubers, whereas the area of land cultivated with tiger nut is becoming very small. This is highly affecting the population of the plant and explains the need to introduce its cultivation in different phytogeographical regions of Egypt. Materials and methods Tubers of C. esculentus were obtained from Wady Elsheh Farm, Assuit Governorate, Egypt, and were cultivated in four different locations during two planting periods. Physical and chemical properties of the soils were determined. In addition, water used for irrigation was analyzed. Moreover, growth and yield parameters were recorded. The 80% methanol extract of powdered tubers was prepared using the ultrasound-assisted extraction, and the antioxidant activity was determined using the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. Results and conclusion The obtained results showed that soil type and water used for irrigation had a significant effect on plant growth, that is, plant height and fresh and dry weight of herb during the two seasons. Moreover, the four extracts of samples obtained from the four locations exerted remarkable antioxidant activity (83.4, 92.4, 90.7, and 65.1%, respectively), which could be attributed to high flavonoids content of the tubers. The soil and water for irrigation at Wadi Elsaeida, Aswan Governorate, and El-Bahrya Oasis are more suitable for the production of C. esculentus tubers.

Background and objective Invertases represent a group of industrially important enzymes that catalyze the breakdown of sucrose into fructose and glucose. The objective of the present work was the production of invertase enzyme from Penicillium spp. using orange peel waste as substrate under optimum conditions, and also immobilization and characterization of invertase using chitin as carrier. Materials and methods The fungal strain Penicillium spp. and Trichoderma viride were studied for invertase production using different agricultural wastes as substrate. Some parameters such as concentrations of substrate, incubation time, and inoculum size affecting invertase produced by Penicillium spp. using orange peel as substrate were investigated. The invertase produced by Penicillium spp. was partially purified with acetone (60%). Different carriers such as chitin, foam, and saw dust were used for invertase immobilization by covalent binding. The characterizations of immobilized invertase on chitin such as substrate concentrations, pH values, temperature, time of the reaction, thermal stability, and some metal ions were determined. Results and conclusion On comparison between production of invertase from Penicillium spp. and T. viride using different agricultural wastes, it was found that Penicillium spp. produced the highest amount of invertase in the presence of 5% w/v orange peel waste as the carbon source (0.63 U/ml). The optimum incubation period for invertase production was observed after seventh day of incubation periods, using two disks 4 mm in diameter, which produced maximum invertase activity of 1.98 U/ml. The crude enzyme from Penicillium spp. was partially purified by 60% acetone and produced 0.44 U/ml, and then immobilized invertase by covalent binding on chitin showed the highest immobilized yield (88.1%). Overall, 5.0 mg of sucrose as substrate gave the highest activity yield. The optimum conditions for immobilized invertase were at pH 6.0, 30°C, after 30 min of the reaction time; the highest immobilization yields of invertase were 93.2, 98.1, and 100.2%, respectively. The immobilized invertase was completely stable at 50°C, for 30 min Moreover, tryptone, alumina, l-serine and hydroxyproline, zinc sulfate, and EDTA enhanced the yield of invertase immobilized with 182.7, 165.1, 137.7, 134.8, 117.6, and 108.2%, respectively.

Background Isatin as a product was first obtained from the oxidation of indigo dye by nitric acid and chromic acids by Otto Linné Erdman and Auguste Laurent in 1841. Objective This study presents the synthesis of some new isatin derivatives and examines their biological activities. Materials and methods 2-Cyano-N’-(5-nitro-2-oxoindolin-3-ylidene)acetohydrazide (2) reacted with some reagents, namely, salicylaldehyde, phenyl isothiocyanate, ethyl chloroacetate, ethyl iodide, ethyl cyanoacetate, thioglycolic acid, phenyl isothiocyanate, malononitrile, and hydrazine hydrate to produce compounds 3, 4, 5, 6, 8, 9, 10, 11, and 12, respectively. Moreover, compound 6 reacted with hydrazine hydrate to produce compound 7. Antimicrobial activities of some newly synthesized compounds were studied. Results Antioxidant, anticoagulant, and fibrinolytic activities of the new synthesized compounds (1–12) were studied. Compound 10 exhibited highest fibrinolytic activity. On the contrary, compound 12 exhibited highest anticoagulant activities. Moreover, it was noticed that compound 9 exhibited highest antioxidant activity. Conclusion In summary, 14 novel isatin derivatives were synthesized and screened for their antioxidant, anticoagulant, and fibrinolytic activities. Some compounds displayed moderate-to-excellent activities such as antioxidant, anticoagulant, and fibrinolytic agents.

Background Herb–drug interaction study, which is the newest area of research, can affect the modern practice of medicine. Aim The present study was designed to explore the herb–drug interaction of Aloe vera gel, an herbal drug used in herbal formulation for hypoglycemic activity, with glimepiride in normal and diabetic rats. Materials and methods Lethal dose 50% studies for the aqueous extract of A. vera were carried out in albino mice up to the dose level of 2000 mg/kg by following ‘up and down method’ of Organization for Economic and Cooperation Development guidelines no. 425 of Committee for the Purpose of Control and Supervision of Experiments on Animals. Overall, 1/5th, 1/10th, and 1/20th doses of the maximum dose tested for lethal dose 50% of the aqueous extract were selected for the experimental study. A. vera (100, 200, and 400 mg/kg, postoperatively) and glimepiride ½ therapeutic dose (TD), 1 TD, and 2 TD (0.036, 0.072, and 0.144 mg/200 g, postoperatively) were administered orally alone as single doses and as well as concomitantly in normal and streptozotocin-induced diabetic rats. Results After the treatment in all the groups, serum glucose levels were determined, and the serum insulin levels were estimated only in the diabetic rats using chemiluminescence assay method. Both A. vera and glimepiride on their own when administered alone showed hypoglycemic effect in normal rats. The hypoglycemic effect observed with combination of A. vera and glimepiride was significantly more compared with either of the drugs given alone. A. vera also augmented the hypoglycemic effect of glimepiride in streptozotocin-induced diabetic rats. Conclusion Administration of A. vera with glimepiride increased the serum insulin levels. It has been concluded that A. vera augmented hypoglycemic effect of glimepiride. There was a herb–drug interaction that necessitates dose readjustment of glimepiride and monitoring of glucose levels to avoid hypoglycemic condition.

Background and objective Pectin-degrading enzymes applied in the food industries are preferred to be obtained from fungal origin because fungi are potent producers of pectic enzymes and the optimal pH of fungal enzymes is very close to the pH of many fruit juices, ranging from pH 3.0 to 5. Pectinolytic enzymes, have several industrial applications in different industries such as food industries to concentrate fruit juices. They increased the yield of fruit juice from the pulp and removal of haze from juices to get a clear product. Research to find microorganisms to produce high-quality polygalacturonase (PGase) and technical constraint include supply of cheap and pure raw materials needed to produce inexpensive enzymes. Utilization of agroindustrial residues offers potential benefits for solid-state fermentation, which is attractive for the implementation of sustainable bioprocesses. Materials and methods Fungal strain screening for PGase production was studied in 250 ml Erlenmeyer flasks containing 5 g of tested substrate moistened to 50% (v/w, ml/g) with distilled water. One milliliter of spore suspension (10⁶ spores) from each fungus was used as inoculum. The cultures were incubated at 30°C for 4 days. At the end of the incubation period, 100 ml of distilled water was added to each flask, blended by shaking at 150 rpm for 30 min, and harvested by filtration. The filtrates were saved as sources of crude enzyme. The selected fungal strain and substrate were incubated for 120 h at 30°C and culture was taken at 24 h intervals to detect the optimum incubation period. Sugar beet pulp was moistened to different moisture levels, that is, 1 : 1, 1 : 2, 1 : 3, and 1 : 4 (v/w) under the optimum incubation period to determine the more suitable moisture content for enzyme production. Sodium phosphate buffer at 0.1 M was used for adjusting the initial pH of fermentation medium to different values from 3.5 to 7.5 to study the effect of pH on enzyme secretion. The fungus was incubated under different temperatures, that s, 20, 25, 30, 35, and 40°C to study the temperature effect on enzyme production. Inorganic nitrogen sources (at level 0.92 mg N/g solid substrate) were applied in the fermentation medium to study their effect on enzyme yield. Results and conclusion Aspergillus awamori NRC-F18 showed promising PGase’ production activity than other fungi screened. The study showed that the fungus gave promising results when the moisture content was adjusted to 70% (v/w), initial pH value 5.0, and incubation temperature at 35°C for 72 h. The enzyme activity was increased when urea was the sole nitrogen source at a level of 0.92 mg/g solid substrate supplemented to fermentation medium. Under the above conditions, 396.4 U/g original substrate was obtained. A study on the obtained PGase revealed that it has an optimum pH that ranged from 4.5 to 5.5, as well as it gave the highest activity when incubated at 50°C. Eighty percent ammonium sulfate (w/v) was applied to precipitate enzyme protein, as 24% of total protein involved 61% of total PGase activity obtained with a specific activity of 36.94 U/mg protein against 12.8 U/mg protein in the crude culture supernatant. After fermentation the mixture from unutilized raw material and fungal biomass after enzyme elution was 76% (w/w) from the original substrate dry weight involving 14.2% protein related to 9.2% before beet pulp fermentation which could be utilized as feedstuff component in rations for ruminant feed.

Background Red beet (Beta vulgaris L.) is the most important edible crop that belongs to the family Amaranthaceae. It is considered as an excellent source of foliate and manganese. It contains betalains, which are considered as natural pigments consisting of two major components, the yellow betaxanthin and violet betacyanin. Objectives In this paper, the effect of different light qualities [white, blue, green, red, and ultraviolet (UV)] on the red beet extract content was examined. The main aim of this study was to choose the light quality which will elevate betalains. Materials and methods Red beet seeds were well sterilized and germinated on Murashigue and Skoog basal medium. After 4 weeks, the germinated seedlings (explants) were exposed to different wave lengths. Three replicates for each wavelength treatment were collected after 10, 20, and 30 days. Regarding UV treatment, cultures were exposed to UV rays type C for 10, 20, or 30 min, and three replicates for each time period were collected. Fresh weight of each explants was measured and stored at −20°C till further usage. Overall, 0.2 g of fresh weight was used for extraction using 2 ml extraction solvent (80 ml methanol+20-ml sterilized distilled water+100 μl phosphoric acid). The antioxidant activity, total phenols, and betalains were determined using spectrophotometer. Results and conclusion The highest values of both fresh weight and free radical scavenging capacity of 2,2-diphenyl-1-picrylhydrazyl percentage were recorded with exposing the cultures to the blue light for 30 days or the exposure to UV rays for 30 min (1.285 and 0.746 g and 42.27 and 43.88%, respectively). It was obviously recorded that exposing the cultures to the red light for 10 days or exposing them to the UV rays for 10 min gave the highest values of the total phenol (1.54 and 0.88 mg GAE/g FW, respectively). The highest value of betalains (Betacyanin and Betaxanthin) was recorded with exposing the cultures to the red light for 30 days (0.12 and 0.077 mg/g FW, respectively).

Background Osteoporosis, chronic diseases, or conditions that may start early in the premenopausal period have become a real well-being medical issue worldwide. Aim The aim was to assess the accuracy of Osteoporosis Self-Assessment Tool (OST) score as a screening method for detection of osteoporosis among Egyptian premenopausal women compared with dual-energy radiographic absorptiometry. Participant and methods This was a retrospective cross-section study including 539 premenopausal Egyptian women, and their age ranged from 20 to 44 years. They underwent evaluation by dual-energy X-Ray absorptiometry examination of the left femoral neck at the ‘Bone Densitometry Unit’ of the ‘Medical Excellence Research Center (MERC)’, ‘National Research Centre (NRC)’, and then BMI and OST score were calculated from the data. Results The cutoff value of OST among premenopausal women was 7.5 to detect the risk of osteoporosis using the receiver operating characteristic curve, with 71% area under the curve (P<0.000), 71% sensitivity, 59% specificity, 65% accuracy, 63% positive predictive value, and 67% negative predictive value. Any form of bone loss ‘osteopenia or osteoporosis’ could be suspected if there is decreased BMI in the presence of risk factors. Conclusion The Egyptian premenopausal women OST score is 7.5. If it is lower this value, osteoporosis will be predict and needs further management..

Background and objectives L-asparaginase is a therapeutic enzyme used for the treatment of hematopoietic diseases, for example, acute lymphoblastic leukemia. It has many applications other than as an anticancer agent, which includes in the treatment of autoimmune diseases, infectious diseases, antimicrobial property, canine and feline cancers. The aim of this study is to increase the production level of L-asparaginase by the cloning and expression of Bacillus subtilis L-asparaginase (Asp) gene in Escherichia coli. Materials and methods PCR was used for the amplification of Asp gene of B. subtilis. Asp gene was cloned with the blunt vector pJET1.2 under the control of T7 or lacUV5 promoters. Transformation of both plasmids was done in E. coli JM 107. L-asparaginase was determined in E. coli JM 107 recombinant strains. Results Bacillus Asp gene was amplified using PCR and the primers were deduced from the published ansA sequence. PCR program was optimized. The PCR product (1112 bp DNA fragment containing the Asp gene) was detected, purified, and sequenced. The DNA sequence including the complete Asp CDS sequence was deposited in GenBank (GenBank accession number KJ642620.1). The amplicon was cloned using the blunt vector pJET1.2 under the control of T7 or lacUV5 promoters. The recombinant plasmids containing the Asp gene were transformed and expressed into E. coli JM 107. The expression level of Asp in the recombinant stains was increased up to 22 U/ml, which is 2.5-fold higher than that of E. coli JM 107 wild type. The vector promoters had regulatory effect on L-asparaginase production, where the activity under the control of T7 promoter was increased by 47% compared with that of lacUV5 promoter. Conclusion L-asparaginase production could be improved by cloning and by the expression of its corresponding gene in E. coli. The T7 promoter had a higher regulatory effect on L-asparaginase production level than lacUV5 promoter.

Background and objective The emergence of multiple drug-resistant pathogenic microorganisms leads to the search for new, safe, and effective therapeutic substances. Essential oils (EOs) of the cinnamon species are known for their biological antimicrobial and antioxidant properties. Therefore, in our study, the EO extracted from the bark of wild Cinnamomum zeylanicum grown in the green mountains of Oman was investigated to study both the aspects. Materials and methods Chemical composition of the EO was analyzed by gas chromatography–mass spectrometry, and then its antimicrobial potential was tested against different Gram-positive, Gram-negative bacteria and fungi. The minimum inhibitory concentration (MIC) was detected and a further in-depth study on the antimicrobial mode of action of the EO at the MIC concentration was studied, in addition to the determination of the antioxidant potential of the studied EO. Results and conclusion Thirty compounds were identified, and the major constituents were cinnamaldehyde (81.78%), bornyl acetate (5.33%), and cinnamyl acetate (2.82%). The antimicrobial results showed a highly significant activity against all tested microbes. The MIC of our EO ranged from 3.3 μl/ml for Gram-positive bacteria and fungi to 10 μl/ml for Gram-negative ones. The mode of action of EO at MIC concentration showed that it had a strong effect on cell viability, permeability of cell membrane, and leakage of cell constituents such as DNA, RNA, and protein from the cell membrane to outside with the lethal percent reaching 99.99%. Moreover, it was observed that the bactericidal and fungicidal effects act in a dose- and time-dependent manner and they depend on the culture condition. Finally, the EO had a strong antioxidant effect with IC₅₀ equaling 2.3 mg. Cinnamon essential oil has a great potential as a useful agent help in combating resistant microorganisms coupled with healing of wounds according to its antioxidant activity.

Background and objective Fluorinated pyrazoles are widely studied for their anti-inflammatory activities. A new series of fluorinated pyrazole chalcones (4a-g and 5a-g) were synthesized and screened for anti-inflammatory and analgesic activities. Materials and methods Fluorinated pyrazole chalcones were synthesized using polyethylene glycol 400 (PEG-400) as an alternative reaction medium. The anti-inflammatory activity of compounds 4a-g and 5a-g were assessed by the carrageenan paw edema model in rats. Analgesic activity was studied by the tail-flick method in rats. Result and conclusion Among the series, compound 5f was found to be the most potent anti-inflammatory agent, whereas compounds 4c, 4f, 4g, 5a, 5c, 5d, and 5g showed significant anti-inflammatory activity comparable to the reference standard diclofenac sodium. Three compounds 4d, 4f, and 5c showed significant analgesic activity comparable to the reference standard aspirin. From the result, compounds 4c, 4f, 5a, 5c, and 5f have found biologically active members with an interesting dual anti-inflammatory and analgesic profile. Anti-inflammatory activities are supported by the docking study to analyze the possible interactions with the cyclooxygenase-2 enzyme.

Introduction Pharmacoepidemiology is a relatively new scientific topic, and it’s the concepts, methods, and implications are in line with the observations of health studies in the past few decades. It involves the postmarketing investigations, drug utilization review, and the monitoring of both adverse drug reactions and the clinical efficacy of drugs. The Anatomical Therapeutic Chemical classification system as a drug classification method and the defined daily dose (DDD) as a measurement unit have been recommended by WHO for drug utilization studies. Patients and methods This was a prospective cross-sectional study. It was done using the Anatomical Therapeutic Chemical/DDD system and by calculating DDD per 100 bed-days (BDs) for four antibiotics, namely, vancomycin, metronidazole, ceftriaxone, and ceftazidime, used in 78 patients admitted in the internal medicine ICU ward in a hospital of Tehran University of Medical Sciences from April to October 2018. Results The DDD/100 BDs for ceftazidime, ceftriaxone, metronidazole, and vancomycin was 5.96, 4.17, 9.65, and 28.02, respectively. Conclusion Comparing the results of the current study with those of similar studies, it was found that the DDD/100 BDs for ceftazidime, ceftriaxone, and metronidazole is within the normal range, whereas that of vancomycin was much higher than normal.

Objective This study aimed to assess the efficiency of ethyl acetate (EtOAc) extract of Deverra tortuosa (Desf) against Candida albicans. Materials and methods The antifungal activity of the EtOAc extract of D. tortuosa was evaluated using the paper disk diffusion method. The minimum inhibitory concentrations were assessed using broth dilution methods. The antivirulence efficiency of the EtOAc extract was assessed through the evaluation of antibiofilm using the broth dilution method, reduction in fungal dimorphism using spider and GLcNAc media, and assessment of phospholipase activity using egg yolk emulsion medium. The time-kill assay of the EtOAc extract was assessed. Cytotoxicity evaluation of the EtOAc extract against normal cell line MRC-5 using MTT assay was done. The compounds in extract were analyzed using gas chromatography-mass spectrometry. Results and conclusion The inhibition zone of the EtOAc extract of D. tortuosa was 26 mm and minimum inhibitory concentrations was 12.5 mg/ml against C. albicans. The antibiofilm activity of the EtOAc extract showed inhibition of up to 52.2% at a concentration of 25 mg/ml. The EtOAc extract showed a complete reduction in fungal dimorphism and transition between yeast cell and hyphae at concentration of 25 mg/ml. The time-kill assay showed inhibition activity at different concentrations in a dose-dependent manner with −2.6 log¹⁰ CFU after 24 h at 25 mg/ml. Our results support the in vitro potential of D. tortuosa extract as anti-C. albicans. Gas chromatography-mass spectrometry indicated that 23 peaks were observed. Five (74.53%) antimicrobial compounds were present in considerable amounts, including 9-octadecenoic acid (Z)-, methyl ester/hexadecanoic acid, methyl ester/9,12-octadecadienoic acid (Z, Z)-, methyl ester/octadecanoic acid, methyl ester/phenol,2,4-bis (1,1-dimethyl ethyl)-, and another 18 compounds comprised 25.47%. Cytotoxic activity of EtOAc against MRC-5 cells showed little toxicity, with IC₅₀ exceeding 249 µg/ml after 24 h of incubation.