Production, optimization, scale up and characterization of polyhydoxyalkanoates copolymers utilizing dairy processing waste.

The microbial biotransformation using low-cost feedstock to produce biopolymers (degradable), an alternative to petrochemical-based synthesis plastics (non-degradable), can be a beneficial approach towards sustainable development. In this study, the dairy industry processes waste (whey) is used in polyhydroxyalkanoate (PHA) copolymer production. Initial screening suggested that Ralstonia eutropha produced higher PHA as compared to Bacillus megaterium. A central composite rotatable design-based optimization using two process variables (amino acid and tween-80) concentration remarkably influenced PHA co-polymer production under physiological conditions of pH (7), temperature (37 °C), and agitation rate of 150 rpm. High polyhydroxybutyrate (PHB) mass fraction yield of 69.3% was observed as compared to predicted yield of 62.8% from deproteinized whey as feed. The combination of tryptophan (50 mg L-1) and tween-80 (3 mL-1) enhanced R. eutropha mass gain to 6.80 g L-1 with PHB contents of 4.71 g L-1. Further, characterization of PHA and its copolymers was done by ESI-MS, FTIR, and TEM. On upscaling up to 3.0 L, the PHA contents and yields were noted as quite similar by R. eutropha. This study demonstrates that dairy waste processing waste can be potentially utilized as inexpensive feed for producing high content of biopolymers to develop a sustainable system of waste management.

Green Synthesis of Fluorescent Carbon Dots from Annona squamosa Leaves: Optical and Structural Properties with Bactericidal, Anti-inflammatory, Anti-angiogenesis Applications.

A hydrothermal method was employed for green synthesis of fluorescent carbon dots (GCDs) from Annona squamosa leaves. The synthesized GCDs were confirmed by microscopic and spectroscopic techniques such as: High Resolution Transmission Electron Microscopy (HR-TEM), Atomic Force Microscopy (AFM), UV-Vis spectrometry, Fluorescence spectrometry, X-Photoelectron Spectroscopy (XPS), X-ray Diffraction spectroscopy (XRD), and Fourier Transform Infrared Spectroscopy (FTIR). The produced GCDs had shown multiple properties, including massive antibacterial activity at concentration 200 µg/ml. The stabilization of human red blood cells served as a method to assess the anti-inflammatory activity. We also looked at how GCDs affected the angiogenesis process. The density of blood vessels was significantly decreased after treatment with GCDs, according to the results of the Chorio-Allantoic Membrane assay (p < 0.05). As per the study prepared GCDs from fallen leaves of Annona squamosa have multifunctional applications.

Stem Cells: Therapeutic Implications in Chemotherapy and Radiotherapy Resistance in Cancer Therapy.

Cancer stem cells (CSCs) are transformed forms of normal stem cells within heterogeneous mixture of cancer cells. These are mainly responsible for the recurrence of cancer after treatment because of their ability to develop resistance against chemo and radiotherapy due to various factors such as activation of signalling pathways important for self-renewal, DNA repair capacity, microenvironment and expression of ABC transporters. Targeting these mechanisms as potential factors can eliminate CSCs, which eventually decreases cancer recurrence. This review focuses on the characteristics of CSCs, their role in the development of resistance to chemotherapy and radiotherapy along with the therapeutic potential targets for successful elimination of CSC population.

"Before the training I just assumed they've done something bad": Reporting on professional training for pharmacy assistants and pharmacy dispensary technicians on medically assisted treatment of opioid dependence.

BACKGROUND: A study that examined the lived experiences of Medically Assisted Treatment of Opioid Dependence (MATOD) consumers suggested that they had experienced discrimination and stigma in pharmacies in regional Victoria, Australia. To address this, the need for professional training opportunities for Pharmacy Assistants (PAs) and Pharmacy Dispensary Technicians (PTDs) had been emphasised. A research project was undertaken to develop training modules using Social Determinants of Health (SDH) for PAs and PDTs involved in providing MATOD pharmacy services in regional Victoria, and to evaluate their effectiveness. OBJECTIVES: The study aimed to examine and evaluate changes in attitudes and practices amongst PAs and PDTs involved in MATOD services in regional Victoria, Australia and who had undertaken the training modules. METHODS: The paper reports primarily on the in-depth qualitative interviews that were completed after the training with PAs and PTDs. Thematic analysis was employed to code the data. RESULTS: Thematic analysis generated five themes: understanding of the professional role of PAs and PTDs, initial judgements concerning MATOD consumers, reflection on the SDH, training content analysis, and the post-training impact upon Professional Practice. These themes reflected participants' insights with regards both to MATOD consumers and the impact the training itself had had on their professional practice. CONCLUSION: "Consciousness-raising" from participation in the training can positively influence the development of participants' professional attitudes and practices with regards to MATOD service delivery. This development supports that training informed by SDH and ideas of critical reflection can help facilitate the creation of knowledge around the social construction of health and increased understanding of the impacts of language-use, attitudes and behaviour.

Type-1 interferons prolong the lifespan of neutrophils by interfering with members of the apoptotic cascade.

Polymorphonuclear Neutrophils (PMNs) are metabolically highly active phagocytes, present in abundant numbers in the circulation. These active cells take the onus of clearing invading pathogens by crowding at inflammatory sites in huge numbers. Though PMNs are extremely short living and die upon spontaneous apoptosis, extended lifespan has been observed among those cells arrive at the inflammation sites or tackle intracellular infections or face any microbial challenges. The delay/inhibition of spontaneous apoptosis of these short-living cells at the inflammatory core rather helps in combating pathogens. Like many candidates, type-1 interferons (type-1 IFNs) is a group of cytokines predominant at the inflammation site. Although there are some isolated reports, a systematic study is still lacking which addresses the impact of the predominant type of interferon on the spontaneous apoptosis of neutrophils. Here in, we have observed that exposure of these IFNs (IFN-ß, IFN-α & IFN-ω etc) on human neutrophils prevents the degradation of the Bfl1, an important anti-apoptotic partner in the apoptotic cascade. Treatment showed a significant reduction in the release of cytochrome-C in the cytosol, a critical regulator in the intrinsic apoptotic pathway. We also noticed a reduction in the conversion of procaspase -3 to active caspase-3, a crucial executioner caspase towards initiation of apoptosis. Taken together our results show that exposure to interferon interferes with apoptotic pathways of neutrophils and thereby delay its spontaneous apoptosis. These findings would help us further deciphering specific roles if these inflammatory agents are causing any immune-metabolomic changes on PMNs at the inflammatory and infection core.

Pro-inflammatory cytokine Interleukin-1ß (IL-1ß) controls Leishmania infection.

Leishmania is an obligate intracellular parasite uses low pH phagolysosomal compartments of host macrophages as their final abode. IL-1ß is a pro inflammatory cytokine, which is secreted by immune cells to trigger inflammation and this has been found profoundly in the lesions caused by Leishmania pathogens. But the specific role of this cytokine on host cell macrophages during infection has not been fully explored. Here in, we have showed that prolonged exposure of IL-1ß on macrophages increases the parasite burden. Pre-treatment of bone marrow derived macrophages (BMDM) with IL-1ß also generates significantly higher amount of anti-inflammatory cytokine IL-10. As IL-10 plays crucial role in the establishment of infection, enhanced production of IL-10 observed upon IL-1ß treatment could contribute to the progression of the disease. By quantifying the production of Nitric oxide (NO), we further report that the pretreatment of IL-1ß fails to produce the nitric oxide. By measuring the footpad thickness in two different mice strains of differential susceptibility we showed IL-1ß treatment increases parasitic burden. As our results shows that the exposure of IL-1ß helps in disease progression, IL-1ß signalling may be an attractive target for future therapeutic intervention.

Neutrophils: Interplay between host defense, cellular metabolism and intracellular infection.

Neutrophils are short-living innate immune cells present in abundance in the circulation and they provide the first line of defense against infection. Microbicidal effector functions of the immune cells are tightly linked with their metabolic state. Overall knowledge of the association of neutrophil defense with cellular metabolism is still elusive. Recent studies have reported that neutrophil metabolism during granulopoiesis is impacted by the homeostatic process of autophagy. Autophagy is a complex process of which the subtype xenophagy, an antimicrobial autophagic process, clears invading pathogens. Neutrophils, being sentinels of innate immunity, encounter microbes and digest them. Studies on neutrophil antimicrobial autophagy process is still in its primeval state and has not been much explored as in other professional phagocytes. However, several obligate-intracellular pathogens are able to subvert the toxic antimicrobial machineries and utilize neutrophils as their final abodes or "Trojan Horses" for further propagation. In this review, we would provide an insight into the relationship between neutrophil microbicidal effector functions emphasizing on selective antimicrobial autophagy and metabolism, highlighting on some successful pathogens which have evolved ways to subvert or exploit this defense.