-
1.
Update on vitamin D role in severe infections and sepsis.
Cutuli, SL, Ferrando, ES, Cammarota, F, Franchini, E, Caroli, A, Lombardi, G, Tanzarella, ES, Grieco, DL, Antonelli, M, De Pascale, G
Journal of anesthesia, analgesia and critical care. 2024;(1):4
Abstract
Severe infections frequently require admission to the intensive care unit and cause life-threatening complications in critically ill patients. In this setting, severe infections are acknowledged as prerequisites for the development of sepsis, whose pathophysiology implies a dysregulated host response to pathogens, leading to disability and mortality worldwide.Vitamin D is a secosteroid hormone that plays a pivotal role to maintain immune system homeostasis, which is of paramount importance to resolve infection and modulate the burden of sepsis. Specifically, vitamin D deficiency has been widely reported in critically ill patients and represents a risk factor for the development of severe infections, sepsis and worse clinical outcomes. Several studies have demonstrated the feasibility, safety and effectiveness of vitamin D supplementation strategies to improve vitamin D body content, but conflictual results support its benefit in general populations of critically ill patients. In contrast, small randomised clinical trials reported that vitamin D supplementation may improve host-defence to pathogen invasion via the production of cathelicidin and specific cytokines. Nonetheless, no large scale investigations have been designed to specifically assess the impact of vitamin D supplementation on the outcome of critically ill septic patients admitted to the intensive care unit.
-
2.
Phase II Study of the Liposomal Formulation of Eribulin (E7389-LF) in Combination with Nivolumab: Results from the Small Cell Lung Cancer Cohort.
Nishio, M, Murakami, S, Kawakami, H, Okishio, K, Tamiya, M, Kobayashi, H, Fujimoto, D, Sugawara, S, Kozuki, T, Oya, Y, et al
Cancer research communications. 2024;(1):226-235
Abstract
PURPOSE E7389-LF is a liposomal formulation of eribulin that contributes to tumor vascular remodeling. The phase II part of this phase Ib/II study assessed the efficacy/safety of E7389-LF in combination with nivolumab in several disease cohorts; herein, we report results from the small cell lung cancer (SCLC) cohort. EXPERIMENTAL DESIGN Patients with unresectable/measurable SCLC and disease progression with first-line platinum-based chemotherapy with/without an immune checkpoint inhibitor (ICI) were enrolled to receive E7389-LF 2.1 mg/m2 plus nivolumab 360 mg intravenously every 3 weeks. The primary objective of this part was to assess the objective response rate (ORR). Secondary objectives included assessments of safety and progression-free survival (PFS); exploratory assessments included overall survival (OS) and biomarkers. RESULTS Thirty-four patients were enrolled. By the data cut-off date (May 31, 2022), 29 (85.3%) had discontinued. Efficacy/biomarker analyses included 33 patients (1 had their diagnosis changed postenrollment); the ORR of E7389-LF plus nivolumab was 24.2% [95% confidence interval (CI): 11.1-42.3], the median PFS was 3.98 months (95% CI: 2.63-4.40), and, at a median follow-up of 10.6 months, the median OS was not reached (95% CI: not estimable). Notably, 27 of 33 patients (81.8%) had received an ICI as their prior first-line therapy. Treatment-related, treatment-emergent adverse events occurred in 97.1% (any grade) and 82.4% (grade ≥3) of enrolled patients; the most common event was neutropenia. Changes in vascular and immune-related plasma markers were observed. CONCLUSIONS E7389-LF 2.1 mg/m2 in combination with nivolumab 360 mg every 3 weeks showed notable antitumor activity as second-line therapy for SCLC; no new safety signals were observed compared with either agent as monotherapy. SIGNIFICANCE This phase II part of a phase Ib/II study assessed liposomal eribulin (E7389-LF) plus nivolumab in 34 patients with pretreated SCLC; 8 of 33 evaluable patients (including 6/27 pretreated with ICIs) had objective responses. The combination was tolerable; increases in vasculature-related biomarkers tended to correlate with responses.
-
3.
Developmental Impacts of Epigenetics and Metabolism in COVID-19.
Naik, N, Patel, M, Sen, R
Journal of developmental biology. 2024;(1)
Abstract
Developmental biology is intricately regulated by epigenetics and metabolism but the mechanisms are not completely understood. The situation becomes even more complicated during diseases where all three phenomena are dysregulated. A salient example is COVID-19, where the death toll exceeded 6.96 million in 4 years, while the virus continues to mutate into different variants and infect people. Early evidence during the pandemic showed that the host's immune and inflammatory responses to COVID-19 (like the cytokine storm) impacted the host's metabolism, causing damage to the host's organs and overall physiology. The involvement of angiotensin-converting enzyme 2 (ACE2), the pivotal host receptor for the SARS-CoV-2 virus, was identified and linked to epigenetic abnormalities along with other contributing factors. Recently, studies have revealed stronger connections between epigenetics and metabolism in COVID-19 that impact development and accelerate aging. Patients manifest systemic toxicity, immune dysfunction and multi-organ failure. Single-cell multiomics and other state-of-the-art high-throughput studies are only just beginning to demonstrate the extent of dysregulation and damage. As epigenetics and metabolism directly impact development, there is a crucial need for research implementing cutting-edge technology, next-generation sequencing, bioinformatics analysis, the identification of biomarkers and clinical trials to help with prevention and therapeutic interventions against similar threats in the future.
-
4.
Roles of autophagy in killing of mycobacterial pathogens by host macrophages - Effects of some medicinal plants.
Tatano, Y, Shimizu, T, Sano, C, Tomioka, H
European journal of microbiology & immunology. 2024;(1):26-36
Abstract
Autophagy is a cellular stress-induced intracellular process, through which damaged cellular components are decomposed via lysosomal degradation. This process plays important roles in host innate immunity, particularly the elimination of intracellular pathogens inside host macrophages. A more detailed understanding of the roles of autophagic events in the effective manifestation of macrophagic antimycobacterial activity is needed. Furthermore, the effects of medicinal plants on macrophagic autophagy response to mycobacterial infection need to be clarified. We herein examined the significance of autophagic events in the manifestation of host immunity during mycobacterial infection, by performing a literature search using PubMed. Recent studies demonstrated that autophagy up-regulated macrophage functions related to the intracellular killing of mycobacteria, even when pathogens were residing within the cytoplasm of macrophages. The majority of medicinal plants potentiated macrophagic autophagy, thereby enhancing their antimycobacterial functions. In contrast, most medicinal plants down-regulate the development and activation of the Th17 cell population, which reduces macrophage antimycobacterial activity. These opposing effects of medicinal plants on macrophage autophagy (enhancement) and Th17 cell functions (inhibition) may provide a plausible explanation for the clinical observation of their modest efficacy in the treatment of mycobacterial infections.
-
5.
The anterior chamber of the eye technology and its anatomical, optical and immunological bases.
Berggren, PO, Yang, SN, Shi, Y
Physiological reviews. 2024
Abstract
The anterior chamber of the eye (ACE) is distinct in its anatomy, optics and immunology. This guarantees that the eye perceives visual information in the context of physiology even when encountering adverse incidents like inflammation. In addition, this endows the ACE with the special nursery bed iris enriched in vasculatures and nerves. The ACE constitutes a confined space enclosing an oxygen/nutrient-rich, immune-privileged and less stressful milieu as well as an optically transparent media. Therefore, aside from visual perception, the ACE unexpectedly serves as an excellent transplantation site for different body parts and a unique platform for non-invasive, longitudinal and intravital micro-imaging of different grafts. On the basis of these merits, the ACE technology has evolved from the prototypical through the conventional to the advanced version. Studies using this technology as a versatile biomedical research platform have led to a diverse range of basic knowledge and in-depth understanding of a variety of cells, tissues and organs as well as artificial biomaterials, pharmaceuticals and abiotic substances. Remarkably, the technology turns in vivo dynamic imaging of the morphological characteristics, organotypic features, developmental fates and specific functions of intracameral grafts into reality under physiological and pathological conditions. Here we review the anatomical, optical and immunological bases as well as technical details of the ACE technology. Moreover, we discuss major achievements obtained and potential prospective avenues for this technology.
-
6.
Dietary composition of adult eosinophilic esophagitis patients is related to disease severity.
Eussen, SRBM, Wielders, S, de Rooij, WE, Van Ampting, MTJ, Van Esch, BCAM, de Vries, JHM, Bredenoord, AJ, Vlieg-Boerstra, B
Immunity, inflammation and disease. 2024;(3):e1206
Abstract
BACKGROUND In addition to the elimination diet, dietary composition may influence disease severity in patients with eosinophilic esophagitis (EoE) through modulation of the immune response. AIM: To explore the immunomodulatory role of nutrition before and during elimination diet in adult EoE patients. METHODS Nutritional intake was assessed in 39 Dutch adult EoE patients participating in the Supplemental Elemental Trial (Dutch trial registry NL6014, NTR6778) using 3-day food diaries. In this randomized controlled trial, diagnosed patients received either a four-food elimination diet alone (FFED) or FFED with addition of an amino acid-based formula for 6 weeks. Multiple linear regression analyses were performed to assess associations between the intake of nutrients and food groups per 1000 kCal and peak eosinophil count/high power field (PEC), both at baseline and after 6 weeks. RESULTS At baseline, we found a statistically significant negative (thus favorable) relationship between the intake of protein, total fat, phosphorus, zinc, vitamin B12, folate, and milk products and PEC (p < .05), while calcium (p = .058) and full-fat cheese/curd (p = .056) were borderline (favorably) significant. In contrast, total carbohydrates, prepacked fruit juice, and white bread were significantly positively (unfavorable) related to PEC (p < .05), while ultra-processed meals (p = .059) were borderline (unfavorably) significant. After dietary intervention, coffee/tea were significantly negatively (favorably) related to PEC, hummus/legumes were significantly positively (unfavorably) related with PEC, while peanuts were borderline significantly positively related (p = .058). CONCLUSION Dietary composition may be related to inflammation in adult EoE patients. High-quality and anti-inflammatory diets may be a promising adjuvant therapy in the dietary management of EoE.
-
7.
Targeting ageing with rapamycin and its derivatives in humans: a systematic review.
Lee, DJW, Hodzic Kuerec, A, Maier, AB
The lancet. Healthy longevity. 2024;(2):e152-e162
-
-
Free full text
-
Abstract
Rapamycin and its derivatives (rapalogs) are inhibitors of mTOR, a major regulator of the ageing process. We aimed to summarise the effects of rapamycin and its derivatives on the severity of ageing-related physiological changes and disease in adults. A search across five databases yielded 18 400 unique articles, resulting in 19 included studies. Rapamycin and its derivatives improved physiological parameters associated with ageing in the immune, cardiovascular, and integumentary systems of healthy individuals or individuals with ageing-related diseases. Overall, no significant effects on the endocrine, muscular, or neurological systems were found. The effects of rapamycin or its derivatives on the respiratory, digestive, renal, and reproductive systems were not assessed. No serious adverse events attributed to rapamycin and its derivatives were reported in healthy individuals; however, there were increased numbers of infections and increases in total cholesterol, LDL cholesterol, and triglycerides in individuals with ageing-related diseases. Future studies should assess the remaining unexamined systems and test the effects of long-term exposure to rapamycin and its derivatives.
-
8.
Probiotics intervention in colorectal cancer: From traditional approaches to novel strategies.
Ha, S, Zhang, X, Yu, J
Chinese medical journal. 2024;(1):8-20
-
-
Free full text
-
Abstract
The intestine harbors a large population of microorganisms that interact with epithelial cells to maintain host healthy physiological status. These intestinal microbiota engage in the fermentation of non-digestible nutrients and produce beneficial metabolites to regulate host homeostasis, metabolism, and immune response. The disruption of microbiota, known as dysbiosis, has been implicated in many intestinal diseases, including colorectal cancer (CRC). As the third most common cancer and the second leading cause of cancer-related death worldwide, CRC poses a significant health burden. There is an urgent need for novel interventions to reduce CRC incidence and improve clinical outcomes. Modulating the intestinal microbiota has emerged as a promising approach for CRC prevention and treatment. Current research efforts in CRC probiotics primarily focus on reducing the incidence of CRC, alleviating treatment-related side effects, and potentiating the efficacy of anticancer therapy, which is the key to successful translation to clinical practice. This paper aims to review the traditional probiotics and new interventions, such as next-generation probiotics and postbiotics, in the context of CRC. The underlying mechanisms of probiotic anti-cancer effects are also discussed, including the restoration of microbial composition, reinforcement of gut barrier integrity, induction of cancer cell apoptosis, inactivation of carcinogens, and modulation of host immune response. This paper further evaluates the novel strategy of probiotics as an adjuvant therapy in boosting the efficacy of chemotherapy and immunotherapy. Despite all the promising findings presented in studies, the evaluation of potential risks, optimization of delivery methods, and consideration of intra-patient variability of gut microbial baseline must be thoroughly interpreted before bench-to-bedside translation.
-
9.
Insights Into Inflammatory Bowel Disease and Effects of Dietary Fatty Acid Intake With a Focus on Polyunsaturated Fatty Acids Using Preclinical Models.
Smyth, M, Lunken, G, Jacobson, K
Journal of the Canadian Association of Gastroenterology. 2024;(1):104-114
Abstract
While the aetiology of inflammatory bowel disease (IBD) has been linked to genetic susceptibility coupled with environmental factors, the underlying molecular mechanisms remain unclear. Among the environmental factors, diet and the gut microbiota have been implicated as drivers of immune dysregulation in IBD. Indeed, epidemiologic studies have highlighted that the increase in incidence of IBD parallels the increase in dietary intake of omega-6 (n-6) polyunsaturated fatty acids (PUFAs) and the change in balance of intake of n-6 to n-3 fatty acids. Experimental evidence suggests that the increase in n-6 PUFA intake increases cell membrane arachidonic acid, which is accompanied by the production of pro-inflammatory mediators as well as increased oxidative stress; together, this contributes to the development of chronic inflammation. However, it is also increasingly clear that some of the n-6 PUFA-derived mediators exert beneficial effects depending on the settings and timing of ingestion. In contrast to n-6, when n-3 PUFA eicosapentaenoic acid and docosahexaenoic acid are incorporated into the cell membrane and are metabolized into less pro-inflammatory eicosanoids, as well as strong specialized pro-resolving mediators, which play a role in inflammation cessation. With a focus on preclinical models, we explore the relationship between dietary lipid, the gut microbiome, and intestinal inflammation.
-
10.
The Killer's Web: Interconnection between Inflammation, Epigenetics and Nutrition in Cancer.
Mecca, M, Picerno, S, Cortellino, S
International journal of molecular sciences. 2024;(5)
Abstract
Inflammation is a key contributor to both the initiation and progression of tumors, and it can be triggered by genetic instability within tumors, as well as by lifestyle and dietary factors. The inflammatory response plays a critical role in the genetic and epigenetic reprogramming of tumor cells, as well as in the cells that comprise the tumor microenvironment. Cells in the microenvironment acquire a phenotype that promotes immune evasion, progression, and metastasis. We will review the mechanisms and pathways involved in the interaction between tumors, inflammation, and nutrition, the limitations of current therapies, and discuss potential future therapeutic approaches.