The present study aimed to develop the synthesis of zinc oxide nanoparticles (ZnO-NPs) using the green method, with Aloe barbadensis leaf extract as a stabilizing and capping agent. In vitro antitumor cytotoxic activity, as well as the surface-functionalization of ZnO-NPs and their drug loading capacity against doxorubicin (DOX) and gemcitabine (GEM) drugs, were also studied. Morphological and structural properties of the produced ZnO-NPs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersion X-ray diffraction (EDX), UV-Vis spectrophotometry, Fourier-transform infrared analysis (FTIR), and X-ray diffraction (XRD). The prepared ZnO-NPs had a hexagonal shape and average particle size of 20–40 nm, with an absorption peak at 325 nm. The weight and atomic percentages of zinc (50.58% and 28.13%) and oxygen (26.71% and 60.71%) were also determined by EDAX (energy dispersive x-ray analysis) compositional analysis. The appearance of the FTIR peak at 3420 m^–1 confirmed the synthesis of ZnO-NPs. The drug loading efficiency (LE) and loading capacity (LC) of unstabilized and PEGylated ZnO-NPs were determined by doxorubicin (DOX) and gemcitabine (GEM) drugs. DOX had superior LE 65% (650 mg/g) and higher LC 32% (320 mg/g) than GEM LE 30.5% (30 mg/g) and LC 16.25% (162 mg/g) on ZnO-NPs. Similar observation was observed in the case of PEG-ZnO-NPs, where DOX had enhanced LE 68% (680 mg/g) and LC 35% (350) mg/g in contrast to GEM, which had LE and LC values of 35% (350 mg/g) and 19% (190 mg/g), respectively. Therefore, DOX was chosen to encapsulate nanoparticles, along with the untreated nanoparticles, to check their in vitro antiproliferative potential against the triple-negative breast cancer (TNBC) cell line (MDA-MB-231) through the MTT (3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) assay. This drug delivery strategy implies that the PEGylated biogenically synthesized ZnO-NPs occupy an important position in chemotherapeutic drug loading efficiency and can improve the therapeutic techniques of triple breast cancer.

Pyrazinamide (PZA) is an important component of first-line drugs because of its distinctive capability to kill subpopulations of persistent Mycobacterium tuberculosis (MTB). The prodrug (PZA) is converted to its active form, pyrazinoic acid (POA) by MTB pncA-encoded pyrazinamidase (PZase). Mutation in pncA is the most common and primary cause of PZA resistance. The aim of the present study was to explore the molecular characterization of PZA resistance in a Pashtun-dominated region of Khyber Pakhtunkhwa, Pakistan. We performed drug susceptibility testing (DST) on 753 culture-positive isolates collected from the Provincial Tuberculosis Control Program Khyber Pakhtunkhwa using the BACTEC MGIT 960 PZA method. In addition, the pncA gene was sequenced in PZA-resistant isolates, and PZA susceptibility testing results were used to determine the sensitivity and specificity of pncA gene mutations. A total of 69 isolates were PZA resistant (14.8%). Mutations were investigated in 69 resistant, 26 susceptible and one H37Rv isolates by sequencing. Thirty-six different mutations were identified in PZA-resistant isolates, with fifteen mutations, including 194_203delCCTCGTCGTG and 317_318delTC, that have not been reported in TBDRM and GMTV Databases and previous studies. Mutations Lys96Thr and Ser179Gly were found in the maximum number of isolates (n = 4 each). We did not detect mutations in sensitive isolates, except for the synonymous mutation 195C > T (Ser65Ser). The sensitivity and specificity of the pncA sequencing method were 79.31% (95% CI, 69.29 to 87.25%) and 86.67% (95% CI, 69.28 to 96.24%). Mutations in the pncA gene in circulating isolates of geographically distinct regions, especially in high-burden countries, should be investigated for better control and management of drug-resistant TB. Molecular methods for the investigation of PZA resistance are better than DST.

The supplementation of Selenium-enriched probiotics is effective in reducing oxidative stress and maintaining meat quality stability in broiler chicken especially under heat stress. An experimental study was conducted to perform Comparative analysis of Selenium yeast with inorganic Se in broilers under heat stress. A total of 120 broilers chicks of one day were assigned to 4 groups each consisting 30 chicks fed on same basal diet but different selenium sources. The basal diet of group D1 was not supplemented with Se source (Negative control), group D2 basal diet was supplemented with inorganic selenium (Sodium selenite 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase), group D3 basal diet was supplemented with commercially available organic selenium (Seleno-methionine 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase) and group D4 basal diet was supplemented with self-developed organic selenium (Se-enriched yeast 0.22mg/Kg starter phase and 0.15mg/Kg finisher phase). The performance parameters i.e. feed intake (FI), live body weight (BW) and FCR were not significantly (p>0.05) effected by selenium supplementation in the starter phase but were significantly (p<0.05) effected in the finisher phase. Selenium supplementation significantly (p<0.05) effected serum Se level in different supplemented groups. Higher serum Se value (58.20±0.06) was recorded in D4 group. Similarly significantly lower selenium value was recorded for D4 and higher was recorded for D1 (11.36±0.08). However lower serum Paraoxonase (PON) value was recorded for D4 (13.24±0.01) and higher for D1 (13.33±0.03). Comparatively self-developed Se enriched yeast increased the Se accumulation and improved antioxidant system. Glutathione peroxidase (GPx) was found higher in D4 (12.333±0.03) followed by D3, D2 and D1 respectively. Whereas superoxide dismutase (SOD) was significantly lower (p<0.05) in D4 (0.1437±0.003) followed by D3 (0.1457±0.002). Selenium supplementation increased the bird’s survival rate. Birds fed on Se enriched yeast showed higher Se deposition and better antioxidant capacity as compared to other sources of selenium. Se-enriched yeast displayed an improved result on Se deposition in tissues, and oxidative capacity, meat tenderness and immune response level as compared to other sources of selenium.

Glycosylation, a posttranslational modification, has a major role in recombinant anticancer therapeutic proteins, as most of the approved recombinant therapeutics are glycoproteins. The constant amino acid sequence of therapeutics determines the enzymatic activity, while the presence of glycans influences their pharmacokinetics, solubility, distribution, serum half-life, effector function, and binding to receptors. Glycoproteins expressed in different expression systems acquire their own oligosaccharides, which increases the protein diversity. The heterogeneity of glycans creates hurdles in downstream processing, ultimately leading to variable anticancer therapeutic efficacy. Therefore, glycoproteins require an appropriate expression system to obtain structurally and functionally identical glycans, as in humans. In many expression systems, the N-glycosylation pathway remains conserved in the endoplasmic reticulum, but divergence is observed when the protein enters the Golgi complex. Hence, in recent decades, numerous approaches have been adopted to engineer the Golgi's N-glycosylation pathway to attain human-like glycans. Several researchers have tried to engineer the N-glycosylation pathway of expression systems. In this review, we examine the glycosylation pattern in various expression systems, along with emerging technologies for glycosylation engineering of anticancer therapeutic drugs. Cancer Res; 78(11); 1–12. ©2018 AACR.

In this article, a new Multi-Layered mamdani fuzzy inference system (ML-MFIS) is propound for the Assessment of Efficient Load Balancing (ELB). The proposed ELB-ML-MFIS expert System can categorise the level of ELB in Cloud computing into Excellent, Normal or Low. ELB-ML-MFIS Expert System for ELB in cloud computing is developed under the guidelines from the Microsoft Organization and Pakistan’s Punjab Information Technology Board (PITB) Standard. ELB-ML-MFIS Expert System uses input Cloud Computing parameters such as Data-Center, Virtual-Machine, and Inter –of-Things (IOT) for different layers. This article also analyses the intensities of the Parametres and the results achieved by using the Proposed ELB-ML-MFIS Expert System. All these parameters and results are discussed with the experts of Pakistan’s Punjab Information Technology Board (PITB), Lahore. The accuracy of the proposed ELB-ML-MFIS Expert System is more accurate as compared to other approaches used for it.

The clinical application of microRNAs in modern therapeutics holds great promise to uncover molecular limitations and conquer the unbeatable castle of cancer metastasis. miRNAs play a decisive role that regulating gene expression at the post-transcription level while controlling both the stability and translation capacity of mRNAs. Specifically, miR34a is a master regulator of the tumor suppressor gene, cancer progression, stemness, and drug resistance at the cell level in p53-dependent and independent signaling. With changing, trends in nanotechnology, in particular with the revolution in the field of nanomedicine, nano drug delivery systems have emerged as a prominent strategy in clinical practices coupled with miR34a delivery. Recently, it has been observed that forced miR34a expression in human cancer cell lines and model organisms limits cell proliferation and metastasis by targeting several signaling cascades, with various studies endorsing that miR34a deregulation in cancer cells modulates apoptosis and thus requires targeted nano-delivery systems for cancer treatment. In this sense, the present review aims to provide an overview of the clinical applications of miR34a regulation in targeted therapy of cancer.