Synthesis and biological evaluation of some heterocyclic compounds

Cancer is one of the most striking diseases that has a potential impact on human health with high mortality rate. During the last century many anticancer agents have emerged but unfortunately, these agents could not provide effective solutions for cancer treatment due to side effects and resistance. All over the world, asking for new anticancer agents is still a major goal for medicinal chemists. Pyrrole and pyrrolo[2,3-d]pyrimidine scaffolds are very interesting bioactive core exhibiting several biological activities as anticancer, anti-inflammatory, antimicrobial activities. Herein, we highlighted on the anticancer activity of the pyrrole and pyrrolo[2,3-d]pyrimidine derivatives which are reported to possess anticancer activity and many of them are in market or still in clinical trials. This work deals with design and synthesis of new pyrrole and pyrrolopyrimidine derivatives. The new compounds were screened for their cytotoxic activity against HepG2 and MCF7in vitro. The most active compounds were evaluated for their VEGFR-2 inhibition in vitr

Influence of distinctive Osmoprotectnats foliar spray in alleviating the harmful effects of water stress at sensitive growth stages of Maize (Zea mays L.)

Water availability is becoming a significant concern for crop production worldwide. In light of this, a study was conducted in maize crop to explore the effectiveness of various osmoprotectants including sodium nitroprusside nanoparticles (SNP NP) at a concentration of 90 ppm, melatonin (MEL), at 25 ppm and salicylic acid (SA) at 100 ppm in mitigating the adverse effects of drought, by evaluating their impact on morpho-physiological, biochemical and yield attributes of maize (Zea mays L.). Drought stress was induced by withholding irrigation during both the vegetative and reproductive stages of maize and then drought-stressed plants were foliar sprayed with different osmoprotectants. Results revealed that among the osmoprotectants tested, foliar application of salicylic acid at 100 ppm exhibited the most substantial improvement in morpho-physiological parameters (plant height, stem diameter, leaf number, root length, leaf area index, relative water content, leaf chlorophyll and carotenoid content) as well as biochemical parameteters like proline and soluble protein content increased, and enhanced membrane stability under drought conditions. The use of SA proved outstanding as it led to a remarkable 75% higher biological yield than plants subjected to drought stress. On the other hand, the SA foliar spray was successful, resulting in a 78.8% in grain yield. However, the extent of improvement varied depending on the growth stage at which the osmoprotectants were applied. While the foliar application of osmoprotectants showed promising results during the vegetative phase than the reproductive phase of maize. Nonetheless, the osmoprotectants' foliar spray exhibited a yield advantage by preserving photosynthetic pigments and the maize plants' ability to produce seeds under drought stress

Scrutinized System Calls Information Using J48 And Jrip For Malware Behaviour Detection

Malware is considered as one of most emerging threats due to Cybercriminals work diligently to make most of the part of the users’ network of computers as their target. A number of researchers keep on proposing the various alternative framework consisting detection methods day by days in combating activities such as single classification and the rule-based approach. However, such detection method still lacks in differentiate the malware behaviours and cause the rate of falsely identified rate, i.e., false positive and false negative increased. Therefore, integrated machine learning techniques comprise J48 and Jrip are proposed as a solution to distinguish malware behaviour more accurately. This integrated classifier algorithm applied to analyse, classify and generate rules of the pattern and program behaviour of system call information in which, the legal and illegal behaviours could identify. The result showed that the integrated classifier between J48 and Jrip significantly improved the detection rate as compared to the single classifier

Influence of rice husk ash-derived silica nanoparticles on sweetcorn (Zea mays L. sachharata) seed germination

In agriculture, the utilization of nanomaterials has garnered significant global attention. This research adopts a pioneering approach to investigate the influence of nanosilica on the germination dynamics of sweetcorn seeds. The present study aimed to synthesize and analyze an amorphous nano-silica material using rice husk ash (RHA) and its impact on the germination of sweetcorn seeds (Zea mays L. sachharata). The extracted nano-silica particles dispersed into six rates of suspensions (0, 100, 200, 300, 400 and 500 ppm) were used to study their effects on seed germination. The synthesized amorphous nano-silica was  determined for size, shape, and elemental content. The amorphous nature of the silica sample was confirmed by transmission electron microscopy-selected area electron diffraction (ED) patterns and X-ray diffraction (XRD), whereas siloxane and silanol groups were mainly detected by Fourier-transform infrared (FT-IR) spectroscopy. Image obtained using scanning electron microscopy (SEM) revealed the presence of original nanoparticles alongside secondary microparticles, probably due to agglomeration. Particles in the extracted amorphous silica had an average diameter of 35 nm. Nano-silica powder was amorphous, according to XRD. As per the EDS analysis, the extracted silica sample is 96.87 % pure. The amorphous nano-silica significantly boosted germination metrics such as germination percentage, germination index, vigour index, and mean germination time of sweetcorn. With the addition of 300 ppm nano-silica, the germination percentage increased by 40.1%, the germination index by 96%, and the vigor index by 120% over control seeds. The improvement of seed germination by amorphous nano-silica in sweetcorn implies a potential application of nano-silica in seed germination

Ameliorative Effect of Mesenchymal Stromal Cells on Diabetic Nephropathy in Male Rats

Both types of diabetes mellitus (DM) are recognized by the destruction of pancreas or deficient function of Islets’ cells causing several complications. Diabetes mainly affect the kidney leading to diabetic nephropathy (DN) in the late renal stage, which caused higher mortality in diabetic patients. Since diabetic disease appearance, nephropathy may be observed in patients with type 1 or 2 diabetes. Recently, cell culture can be used in the regenerative medicine as a new method for treating diabetes and DN. Therefore, the aim of the current study was to prove the beneficial effect of mesenchymal stromal cells (MSCs) transplantation on DN during the early stage. Male rats were randomized in 3 groups (each 20 rats): the 1st group was normal rats, while the 2nd was streptozotocin (STZ) diabetic rats and the 3rd was diabetic rats treated with a single intravenous dose of bone marrow mesenchymal stromal cells (BM-MSCs) after 3 days from STZ induction. Results indicated that STZ induced DN represented by weight loss, hyperglycemia, hypoinsulineamia, decreased glycated hemoglobin, leukocytosis and impairment of kidney function and oxidative stress in kidney tissue. After BM-MSCs treatment, blood glucose level was improved, renal function was retained, body weight loss was decreased, insulin level and HBA1C percent were ameliorated with improved oxidative stress in kidney tissue. BM-MSCs have the capacity to regenerate and differentiate into insulin- producing cells improving DM and DN

Prevalence and Risk Factors of Hepatitis B Virus among Pregnant Women in Jazan Region- Kingdom of Saudi Arabia

Background: Hepatitis B virus is one of the major etiological agents for parenterally acquired hepatitis. Viral hepatitis during pregnancy is associated with high risk of maternal complications. This study was conducted to determine the prevalence of HBV infection in pregnant women, and to find out its associated risk factors in Jazan region south KSA. Patients & Methods: A random sample of 537 pregnant females who attended Jazan general hospital and randomly selected primary health care centers in Jazan region - before 38 weeks of gestation - constituted the target population of the present study. All women were screened for HBsAgd by using HBsAg Rapid Test Device (ACON). Results: The overall prevalence of HBV virus among the women was found to be 4.1% (95% CI: 2.7 - 6.1). The prevalence of HBV according to age showed that women less than 20 years are free of HBV, whereas for other age groups HBV prevalence is found to increase with increase in age. Regarding the associated risk factors, women  with  history of hospitalization, and  jaundices showed a significant association with anti- HBV seropositive. Dental histories, blood transfusion and history of surgery did not prove significant association with  HBV. Conclusion: Prevalence of Hepatitis B virus infection in pregnant ladies was 4.1%. Past history of hospitalization and jaundices are important risk factors for transmission of infection. The study suggests expansion of the Hepatitis B vaccination program to reduce the risk of HBV among pregnant women. Key words: Hepatitis B virus, Pregnancy, Prevalence, Risk factors

Physical pegylation enhances the cytotoxicity of 5-fluorouracil-loaded PLGA And PCL nanoparticles.

Purpose : The main goal of this study is to evaluate the impact of physical incorporation of polyethylene glycol (PEG) into 5-fluorouracil (5-FU)-loaded polymeric nanoparticles (NPs). METHODS: The 5-FU-loaded NPs were prepared utilizing a simple double emulsion method using polycaprolactone (PCL) and polylactic-co-glycolic acid (PLGA) with or without PEG 6000. The surface charge, particle size, and shape of NPs were evaluated by standard procedures. Both Fourier Transform Infrared Spectroscopy and X-ray diffraction spectra of the 5-FU loaded NPs were compared against the pure 5-FU. The in vitro release profile of 5-FU from the NPs was monitored by the dialysis tubing method. Cell death and apoptosis induction in response to 5-FU NP exposure were measured by MTT and Annexin-V/7-amino-actinomycin D (7-AAD) assays, respectively, in Daoy, HepG2, and HT-29 cancer cell lines. RESULTS: The 5-FU loaded NPs were found to be spherical in shape with size ranging between 176±6.7 and 253.9±8.6 nm. The zeta potential varied between -7.13± 0.13 and -27.06±3.18 mV, and the entrapment efficiency was between 31.96% and 74.09%. The in vitro release of the drug followed a two-phase mode characterized by rapid release in the first 8 hrs followed by a period of slow release up to 72 hrs with composition-based variable extents. Cells exposed to NPs demonstrated a significant cell death which correlated with the ratio of PEG in the formulations in Daoy and HepG2 cells but not in HT-29 cells. Formulations (F1-F3) significantly induced early apoptosis in HT-29 cell lines. CONCLUSION: The physical PEGylation significantly enhanced the entrapment and loading efficiencies of 5-FU into NPs formulated with PLGA and PCL. It also fostered the in vitro cytotoxicity of 5-FU-loaded NPs in both Daoy and HepG2 cells. Induction of early apoptosis was confirmed for some of the formulations

Novel docetaxel chitosan-coated PLGA/PCL nanoparticles with magnified cytotoxicity and bioavailability

In the present study, docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) nanoparticles were successfully prepared and coated with chitosan (CS). The prepared nanoparticles (NPs) were evaluated for their particle size, zeta potential, particle morphology, drug entrapment efficiency (EE%), and in vitro drug release profile. The anticancer activity of DTX-loaded NPs was assessed in human HT29 colon cancer cell line utilizing MTT assay. The pharmacokinetics of DTX-loaded NPs was monitored in Wistar rats in comparison to DTX solution. The prepared NPs exhibited particle sizes in the range 177.1 ± 8.2-287.6 ± 14.3 nm. CS decorated NPs exhibited a significant increase in particle size and a switch of zeta potential from negative to positive. In addition, high EE% values were obtained for CS coated PCL NPs and PLGA NPs as 67.1 and 76.2%, respectively. Moreover, lowering the rate of DTX in vitro release was achieved within 48 h by using CS coated NPs. Furthermore, a tremendous increase in DTX cytotoxicity was observed by CS-decorated PLGA NPs compared to all other NPs including DTX-free-NPs and pure DTX. The in vivo study revealed significant enhancement in DTX bioavailability from CS-decorated PLGA NPs with more than 4-fold increase in AUC compared to DTX solution. In conclusion, CS-decorated PLGA NPs are a considerable DTX-delivery carrier with magnificent antitumor efficacy

Primary Fibrosarcoma of the Testicle with Puzzling Post-surgery Presentation: Mimicking Recurrence

Sarcomas of the testis are extremely rare tumors, their incidence being difficult to assess accurately. The authors report a case of a 21-year-old male, presented with painless scrotal swelling that increased in size insidiously within three months. The examination revealed a 10 cm right testicular swelling—hard, not tender and oval in shape. Testicular ultrasound revealed right heterogenous testicular mass. Tumor markers (Human chorionic gonadotrophin (HCG) and alpha fetoprotein) were normal. CT chest and abdomen were normal. Radical orchidectomy was done through an inguinal approach. Histopathology showed testicular fibrosarcoma with spindle cells. After one month, the patient noticed reappearance of a swelling in the right hemiscrotum. Right inguinal exploration with massive resection of the recurrent scrotal mass was done. Histopathology revealed inflammatory process dominated by stitch granuloma. In conclusion, the recurrence rate of testicular sarcomas is high following radical orchidectomy, but still there was a place of non-malignant massthat looks like recurrence; it might occur like nonspecific inflammatory mass and stich granuloma

Effectiveness of exercise and protein supplementation intervention on body composition, functional fitness, and oxidative stress among elderly Malays with sarcopenia

Sarcopenia, characterized as muscle loss that occurs with aging, is a major health problem in an aging population, due to its implications on mobility, quality of life, and fall risk. Protein supplementation could improve the physical fitness by increasing protein anabolism, and exercise has a documented evidence of positive effect on functional status among the elderly. However, the combined effect of both protein supplementation and exercise has not been investigated among sarcopenic elderly in the Asian population. Thus, this study aimed to determine the effectiveness of exercise intervention and protein supplementation either alone or in combination for 12 weeks, on body composition, functional fitness, and oxidative stress among elderly Malays with sarcopenia. Sixty five sarcopenic elderly Malays aged 60-74 years were assigned to the control group, exercise group (ExG), protein supplementation group (PrG), or the combination of exercise and protein supplementation group. A significant interaction effect between body weight and body mass index (BMI) was observed, with the PrG (-2.1% body weight, -1.8% BMI) showing the highest reductions. Further, there was a decrease in % body fat (-4.5%) and an increase in fat-free mass (kg) (+5.7%) in the ExG after 12 weeks (P < 0.05). The highest increments in lower and upper body strength were observed in the PrG (73.2%) and ExG (47.6%), respectively. In addition, the ExG showed a reduction in superoxide dismutase (SOD) levels, and both interventions did not alter either lipid or protein oxidation. In conclusion, the exercise program was found to improve muscle strength and body composition, while protein supplementation reduced body weight and increased upper body strength, among sarcopenic elderly in Malaysia