The infection of the human gastric mucosa by the bacterium Helicobacter pylori can lead to the development of gastritis, gastroduodenal ulcers, and cancer. The factors that determine disease development in a small percentage of infected individuals are still not fully understood. In this thesis, we aimed to identify and functionally characterize novel virulence factors of H. pylori and to understand their effect on host cell responses. In Paper I, we found that JHP0290, an uncharacterized secreted protein of H. pylori, induced macrophage apoptosis concomitant to the release of pro-inflammatory cytokine TNF via the regulation of the Src family of kinases and ERK MAPK pathways. In paper II, we demonstrated that JHP0290 exhibits both proliferative and anti-apoptotic activity, together with a faster progression of the cell cycle in gastric epithelial cells. During these responses, ERK MAPK and NF-κB pathways were activated. Paper III revealed a pro-apoptotic effect of another H. pylori-secreted protein HP1286 in macrophages via the TNF-independent and ERK-dependent pathways. No apoptosis was observed in HP1286-treated T cells or HL60 neutrophil-like cells, suggesting cell-type specific effect of HP1286. In Paper IV, we observed the pro-inflammatory activity of H. pylori secreted protein HP1173 in macrophages. The protein was found to induce TNF, IL-1β, and IL-8 in macrophages through MAPKs, NF-κB, and AP-1 signaling pathways. Furthermore, differential expression and release of JHP0290, HP1286, and HP1173 homologues was observed among H. pylori strains (papers II, III, IV).  Due to their ability to regulate multiple host cell responses, proteins JHP0290, HP1286, and HP1173 could play an important role in bacterial pathogenesis.

The morbidity and societal burden of youth bipolar spectrum disorders (BSD) are high. These disorders are multisystemic in that adult populations there are clear interactions with inflammatory processes and steroidal physiological systems. There are much less data concerning these areas of study in youth populations with BSD. This is surprising given the association of youth-onset BSD with puberty and its associated physiological changes. In this mini-review, we overview the theoretical role of inflammatory processes and steroidal physiological systems in youth BSD, describe the greater literature in adult populations, detail the literature in youth populations when available, and overview current proposed molecular mechanistic pathways and interaction effects based on the available data. We also attend to the interplay of this complex system with body composition and weight gain, an especially important consideration in relation to the role of second generation antipsychotics as the first line treatment for youth with BSD in major clinical guidelines. A developmental model of early onset BSD for boys is hypothesized with pubertal hormonal changes increasing risk for first (hypo-)manic/depressive episode. The dramatic androgen rise during puberty might be relevant for first onset of BSD in boys. A shift from general hypercortisolism driven by glucocorticoid resistance to hypocortisolism with further disease progression is assumed, while increased levels of inflammation are functionally associated with endocrine dysregulation. The interacting role of overweight body habitus and obesity in youth with BSD further indicates leptin resistance to be a central moderator of the dynamic neurobiology of BSD in youth. The intent of this mini-review is to advance our knowledge of youth BSD as multisystemic disorders with important contributions from endocrinology and immunology based on a developmental perspective. This knowledge can influence current clinical care and more importantly inform future research.

<p dir="ltr">The aquaculture industry has experienced remarkable expansion over the past few decades, largely due to the development of modern technologies and intensive farming systems. However, as the industry continues to grow, farming-related and environmental stressors such as overcrowding, poor water conditions and handling have continued to pose major obstacles to the worldwide expansion of this sector. The presence of these stressors affect the growth potential and health of farmed animals leading to significant economic losses. Hence, efficient management of the stress response of farmed species via sustainable means is important to ensure continuous development of the aquaculture sector. This study, therefore, explores the potential of dietary tryptophan supplementation to mitigate stress and improve growth, immune response, and disease resistance in channel catfish (<i>Ictalurus punctatus</i>). The study comprised a 36-day feeding trial where juvenile catfish were fed a tryptophan-supplemented diet under stressed (cortisol-supplemented) and unstressed conditions, followed by a 72-hour disease challenge with <i>Aeromonas hydrophila </i>(vAh). At the end of the study, the results show tryptophan supplementation did not significantly enhance growth or nutrient utilization, likely due to its neuroendocrine effects on feed intake. However, tryptophan demonstrated potential in modulating stress physiology and immune responses, including upregulation of key immune-related genes post-infection and promoting survival against vAh infection. These findings suggest that while tryptophan may not directly improve growth in our specific experimental conditions, its role in stress and immune regulation warrants further investigation, particularly in optimizing its dosage and combination with other dietary additives.</p>