Background: The IκB kinase (IKK) complex, comprising the two enzymes IKKα and IKKβ, is the main activator of the inflammatory transcription factor NF-κB, which is constitutively active in many cancers. While several connections between NF-κB signaling and the oncogene c-Myc have been shown, functional links between the signaling molecules are still poorly studied.Methods: Molecular interactions were shown by co-immunoprecipitation and FRET microscopy. Phosphorylation of c-Myc was shown by kinases assays and its activity by improved reporter gene systems. CRISPR/Cas9-mediated gene knockout and chemical inhibition were used to block IKK activity. The turnover of c-Myc variants was determined by degradation in presence of cycloheximide and by optical pulse-chase experiments.. Immunofluorescence of mouse prostate tissue and bioinformatics of human datasets were applied to correlate IKKα- and c-Myc levels. Cell proliferation was assessed by EdU incorporation and apoptosis by flow cytometry.Results: We show that IKKα and IKKβ bind to c-Myc and phosphorylate it at serines 67/71 within a sequence that is highly conserved. Knockout of IKKα decreased c-Myc-activity and increased its T58-phosphorylation, the target site for GSK3β, triggering polyubiquitination and degradation. c-Myc-mutants mimicking IKK-mediated S67/S71-phosphorylation exhibited slower turnover, higher cell proliferation and lower apoptosis, while the opposite was observed for non-phosphorylatable A67/A71-mutants. A significant positive correlation of c-Myc and IKKα levels was noticed in the prostate epithelium of mice and in a variety of human cancers.Conclusions: Our data imply that IKKα phosphorylates c-Myc on serines-67/71, thereby stabilizing it, leading to increased transcriptional activity, higher proliferation and decreased apoptosis.

Hepatitis C virus remained a public health problem with approximately half of the patients untreated and undiagnosed. Chronic HCV is a leading cause of cirrhosis, fibrosis, hepatocellular carcinoma and other hepatic morbidities. Active HCV has a prevalence rate of about 1% (71 million). By July, 2019, 10 million population of Pakistan was declared to have active HCV infection. According to World Health Organization, 23,720 people died of hepatitis-related complexities in Pakistan in 2016. Individuals with certain types of ABO blood groups were more susceptible to diverse kinds of infections. For instance, blood types A and AB predisposed individuals to severe malaria, while type O conferred resistance to the many of the protozoan agent.

Coronary artery disease (CAD) is the leading cause of sudden death worldwide. Inflammation is proved to be an important player in development of the CAD. Inflammation is directly regulated by the Toll like receptors (TLRs). Susceptibility of CAD is influenced by genetic variations within TLRs and the proteins involved in its signaling cascade. The TIRAP/MAL {TIR domain containing adaptor protein / MyD88 (myeloid differentiation primary response gene 88) adaptor-like} exhibits maximum genetic variations of all adaptor proteins involved in TLR signaling cascade. Susceptibility to a number of diseases can be influenced due to presence of S180L single nucleotide polymorphism (SNP) of TIRAP/MAL. This study was conducted to investigate the functional role of this well characterized S180L polymorphism on susceptibility to CAD among Pakistani patients. A total of 146 Pakistani CAD patients and 147 controls were genotyped by Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) and the data was analyzed by using 2-tailed Chi square (x2) test. The p value ≤ 0.05 was considered to be significant.

Medicinal plants contain phytochemicals that confer therapeutic potentials, allowing plants to perform various biologically significant functions. However, the therapeutic potential of these bioactive metabolites against multidrug-resistant bacteria is limited. Hence, the potential use of rhizopheric bacteria to isolate silver nanoparticles to enhance the potential of bioactive metabolites has been adopted by researchers. Therefore, this research aimed to biogenically produce silver nanoparticles using the rhizospheric soil of Aloe barbadensis miller and to evaluate its impact in regulating the potential of bioactive metabolites produced from the medicinal plant Linum usitatissimum. The powder extract of Linum usitatissimum was macerated under four different environmental conditions including cold maceration, warm maceration, fermented, and unfermented for extraction of metabolites. Macerated extracts were then evaluated for phytochemical detection of bioactive metabolites like alkaloids, steroids, phenols, and saponins. Biogenic AgNPs were primarily confirmed by visible color change from colorless to brown and were further characterized using UV-vis spectroscopy, giving two absorbance peaks at 440 nm and 445 nm. Functional groups attached to biogenic AgNPs were detected by Fourier transform infrared (FTIR) analysis. The crystalline nature of biogenic AgNPs was evaluated by X-ray diffraction (XRD) giving a diffraction peak at angles of around 36°, 46°, 67°, and 77°. The particle size and morphological appearance of biogenic AgNPs were confirmed by Scanning Electron Microscopy (SEM). The total phenolic content of biogenic AgNPs and bioactive metabolites was estimated by the Folin–Ciocalteu (F–C) assay. The antimicrobial efficacy of biogenic AgNPs and bioactive metabolites against MDR bacterial strains was accessed. This research shows that biogenic AgNPs can be used as a strong agent in enhancing the antimicrobial potential of bioactive metabolites against MDR bacteria and they can be investigated for further experimental findings.

The term allergy refers to an exaggerated immune response to a foreign molecule. In a normal healthy individual, this foreign molecule will act as a harmless antigen, as it will be recognized & cleared by the immune system without causing any significant damage to host tissues. In certain individuals, such antigens stimulate immune system in such a way that a series of exaggerated immune response are generated against it, leading to significant tissue injury and damage to the host. Such as exaggerated immune response may also cause death of the patient. Such antigen is termed as an allergen. Allergy is categorised under Immunoglobulin E (IgE) mediated type I hypersensitivity reactions. These reactions occur when an antigen acting as an allergen attacks the immune system of the host and causes excessive stimulation of mast cells and basophils. This is followed by the release of allergy mediators which are responsible for causing local or systemic anaphylaxis, allergic asthma, allergic rhinitis, conjuctivitis. Type I allergens are of various types, the mechanism of action is same; however underlying factors may differ in each type. This article is about pollen allergens, in specific & will discuss the common sources of pollen allergens in Pakistan, the relevance and the factors behind pollen allergy.