Targeting circulating monocytes with CCL2-loaded liposomes armed with an oncolytic adenovirus.

Oncolytic viruses (OVs) selectively replicate in and destroy cancer cells resulting in anti-tumor immunity. However, clinical use remains a challenge because of virus clearance upon intravenous delivery. OV packaging using a nanomedicine approach could overcome this. Here we encapsulate an oncolytic adenovirus (Ad[I/PPT-E1A]) into CCL2-coated liposomes in order to exploit recruitment of CCR2-expressing circulating monocytes into tumors. We demonstrate successful encapsulation of Ad[I/PPT-E1A] into CCL2-coated liposomes that were preferentially taken up by CCR2-expressing monocytes. No complex-related toxicities were observed following incubation with prostate tumor cells and the encapsulation did not affect virus oncolytic activity in vitro. Furthermore, intravenous administration of our nanomedicine resulted in a significant reduction in tumor size and pulmonary metastasis in prostate cancer-bearing mice whereby a 1000-fold less virus was needed compared to Ad[I/PPT-E1A] alone. Taken together our data provide an opportunity to target OVs via circulation to inaccessible tumors using liposome-assisted drug delivery.

Probing the microbial diversity and probiotic candidates from Pakistani foods: isolation, characterization, and functional profiling.

Probiotics represent beneficial living microorganisms that confer physiological, nutritional, and functional advantages to human health, holding significant potential for development of functional foods. This research aimed to isolate, identify, and characterize potential probiotic bacterial strains sourced from fermented and non-fermented foods from Pakistan. A total of 341 bacterial strains were isolated from diverse food samples (81) collected from various regions of Pakistan. Strains were identified using 16S rRNA gene sequencing and phylogenetic analysis. The identified strains belonged to genera Bacillus, Staphylococcus, Microbacterium, Shigella, Micrococcus, Enterococcus, Sporosarcina, Paenibacillus, Limosilactobacillus, Kosakonia, Dietzia, Leclercia, Lacticaseibacillus, Levilactobacillus, Kluyvera, Providencia, Enterobacter, Neisseria, Streptococcus, Acinetobacter, Corynebacterium, Pantoea, Mammaliicoccus, Pseudomonas, Burkholderia, and Alkalihalobacillus. Selected strains were chosen for probiotic assessment, employing existing literature as a guideline. Among these selections, six strains exhibited hemolytic activity, and seven strains displayed resistance to multiple antibiotics, prompting their exclusion from subsequent evaluations. The remaining strains demonstrated auto-aggregation capacities spanning 3.39-79.7%, and displayed coaggregation capabilities with reported food-borne pathogens. Furthermore, nine strains exhibited antimicrobial properties against food-borne pathogens. The assessment encompassed diverse characteristics such as cell surface hydrophobicity, survival rates under varying conditions, cholesterol reduction ability, casein digestion capability, and antioxidant activity. Phylogenomic analysis, digital-DNA DNA hybridization (digi-DDH), and average nucleotide identity (ANI) calculations unveiled novel species potentially belonging to the genera Sporosarcina and Dietzia. Based on these findings, we advocate for the consideration of Staphylococcus cohnii subsp. cohnii NCCP-2414, Lacticaseibacillus rhamnosus NCCP-2569 and Levilactobacillus brevis NCCP-2574 as prime probiotic candidates with the potential for integration into formulation of functional foods. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03903-6.

Understanding Immune Responses to Viruses-Do Underlying Th1/Th2 Cell Biases Predict Outcome?

Emerging and re-emerging viral diseases have increased in number and geographical extent during the last decades. Examples include the current COVID-19 pandemic and the recent epidemics of the Chikungunya, Ebola, and Zika viruses. Immune responses to viruses have been well-characterised within the innate and adaptive immunity pathways with the outcome following viral infection predominantly attributed to properties of the virus and circumstances of the infection. Perhaps the belief that the immune system is often considered as a reactive component of host defence, springing into action when a threat is detected, has contributed to a poorer understanding of the inherent differences in an individual's immune system in the absence of any pathology. In this review, we focus on how these host factors (age, ethnicity, underlying pathologies) may skew the T helper cell response, thereby influencing the outcome following viral infection but also whether we can use these inherent biases to predict patients at risk of a deviant response and apply strategies to avoid or overcome them.