scholarly journals Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1189
Author(s):  
Madhur Wyatt ◽  
K. Leigh Greathouse
Keyword(s):  
Immune Surveillance ◽  
Microbial Transformation ◽  
Colon Carcinogenesis ◽  
Tryptophan Metabolism ◽  
Host Cells ◽  
Therapeutic Approaches ◽  
Therapeutic Modalities ◽  
Indolic Compounds ◽  
Cancer Initiation ◽  
The Impact

Tryptophan metabolism, via the kynurenine (Kyn) pathway, and microbial transformation of tryptophan to indolic compounds are fundamental for host health; both of which are altered in colon carcinogenesis. Alterations in tryptophan metabolism begin early in colon carcinogenesis as an adaptive mechanism for the tumor to escape immune surveillance and metastasize. The microbial community is a key part of the tumor microenvironment and influences cancer initiation, promotion and treatment response. A growing awareness of the impact of the microbiome on tryptophan (Trp) metabolism in the context of carcinogenesis has prompted this review. We first compare the different metabolic pathways of Trp under normal cellular physiology to colon carcinogenesis, in both the host cells and the microbiome. Second, we review how the microbiome, specifically indoles, influence host tryptophan pathways under normal and oncogenic metabolism. We conclude by proposing several dietary, microbial and drug therapeutic modalities that can be utilized in combination to abrogate tumorigenesis.

scholarly journals Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer

2021 ◽  
Author(s):  
K. Leigh Greathouse ◽  
Madhur Wyatt
Keyword(s):  
Immune Surveillance ◽  
Microbial Transformation ◽  
Colon Carcinogenesis ◽  
Tryptophan Metabolism ◽  
Host Cells ◽  
Therapeutic Approaches ◽  
Therapeutic Modalities ◽  
Indolic Compounds ◽  
Cancer Initiation ◽  
The Impact

Tryptophan metabolism, via the kynurenine (Kyn) pathway, and microbial transformation of tryptophan to indolic compounds, are fundamental for host health; both of which are altered in colon carcinogenesis. Alterations in tryptophan metabolism begin early in colon carcinogenesis as an adaptive mechanism for the tumor to escape immune surveillance and metastasize. The microbial community is a key part of the tumor microenvironment and influences cancer initiation, promotion and treatment response. A growing awareness of the impact of the microbiome on tryptophan (Trp) metabolism in the context of carcinogenesis has prompted this review. We first compare the different metabolic pathways of Trp under normal cellular physiology to colon carcinogenesis, in both the host cells and the microbiome. Second, we review how the microbiome, specifically indoles, influence host tryptophan pathways under normal and oncogenic metabolism. We conclude by proposing several dietary, microbial and drug therapeutic modalities that can be utilized in combination to abrogate tumorigenesis.

Alteraciones sistémicas y metabólicas producidas por lesión medular

2019 ◽  
Vol 1 (1) ◽  
pp. 59-75
Author(s):  
Gabriel Guízar Sahagún
Keyword(s):  
Spinal Cord ◽  
Daily Living ◽  
Autonomic Function ◽  
Clinical Presentation ◽  
Scientific Literature ◽  
International Standards ◽  
Therapeutic Approaches ◽  
Cord Injury ◽  
Life Threatening ◽  
The Impact

Besides the well-known loss of motor and sensory capabilities, people with spinal cord injury (SCI) experience a broad range of systemic and metabolic abnormalities including, among others, dysfunction of cardiovascular, respiratory, gastrointestinal, urinary, and endocrine systems. These alterations are a significant challenge for patients with SCI because such disorders severely interfere with their daily living and can be potentially life-threatening. Most of these disorders are associated with impairment of regulation of the autonomic nervous system, arising from disruption of connections between higher brain centers and the spinal cord caudal to the injured zone. Thus, the higher and more complete the lesion, the greater the autonomic dysfunction and the severity of complications.This article summarizes the medical scientific literature on key systemic and metabolic alterations derived of SCI. It provides information primarily focused on the pathophysiology and clinical presentation of these disorders, as well as some guides to prevent and alleviate such complications. Due to the impact of these alterations, this topic must be a priority and diffuse to those involved with the care of people with SCI, including the patient himself/herself. We consider that any collaborative effort should be supported, like the development of international standards, to evaluate autonomic function after SCI, as well as the development of novel therapeutic approaches.

The Management of Post-Tonsillectomy Morbidity in Patients With Sleep Apnoea

2019 ◽  
Vol 70 (10) ◽  
pp. 3738-3740
Keyword(s):  
Day Surgery ◽  
Sleep Apnoea ◽  
Integrative Approach ◽  
Multicenter Studies ◽  
Therapeutic Modalities ◽  
Advantages And Disadvantages ◽  
Obstructive Sleep ◽  
Wide Range ◽  
The Impact ◽  
Surgery Center

The Tonsillectomy in children or adults is an intervention commonly encountered in the ENT (Ear Nose and Throat) and Head and Neck surgeon practice. The current tendency is to perform this type of surgery in major ambulatory surgery centers. Two objectives are thus pursued: first of all, the increase of the patient quality of life through the reintegration into the family as quickly as possible and secondly, the expenses associated with continuous hospitalization are reduced. Any tertiary (multidisciplinary) sleep center must ensure the complete diagnosis and treatment (including surgery) of sleep respiratory disorders. Under these conditions the selection of patients and especially the implementation of the specific protocols in order to control the postoperative complications it becomes essential. The present paper describes our experience of tonsillectomy as treatment for selected patients with chronic rhonchopathy (snoring) and mild to moderate obstructive sleep apnoea. It was presented the impact of antibiotics protocols in reducing the main morbid outcomes following tonsillectomy, in our day surgery center. The obtained results can also be a prerequisite for the integrative approach of the patients with sleep apnoea who were recommended surgical treatment. Considering the wide range of therapeutic modalities used in sleep apnoea, each with its specific advantages and disadvantages, more extensive and multicenter studies are needed. Keywords: post-tonsillectomy morbidity, day surgery center, sleep disorders

scholarly journals Consumption of Select Dietary Emulsifiers Exacerbates the Development of Spontaneous Intestinal Adenoma

2021 ◽  
Vol 22 (5) ◽  
pp. 2602
Author(s):  
Emilie Viennois ◽  
Benoit Chassaing
Keyword(s):  
Intestinal Inflammation ◽  
Tumor Development ◽  
Low Grade ◽  
Gastrointestinal Cancers ◽  
Cancer Initiation ◽  
And Function ◽  
The Impact ◽  
Chronic Intestinal Inflammation ◽  
Low Grade Inflammation ◽  
Intestinal Adenoma

Inflammation is a well-characterized critical driver of gastrointestinal cancers. Previous findings have shown that intestinal low-grade inflammation can be promoted by the consumption of select dietary emulsifiers, ubiquitous component of processed foods which alter the composition and function of the gut microbiota. Using a model of colitis-associated cancer, we previously reported that consumption of the dietary emulsifiers carboxymethylcellulose or polysorbate-80 exacerbated colonic tumor development. Here, we investigate the impact of dietary emulsifiers consumption on cancer initiation and progression in a genetical model of intestinal adenomas. In APCmin mice, we observed that dietary emulsifiers consumption enhanced small-intestine tumor development in a way that appeared to be independent of chronic intestinal inflammation but rather associated with emulsifiers’ impact on the proliferative status of the intestinal epithelium as well as on intestinal microbiota composition in both male and female mice. Overall, our findings further support the hypothesis that emulsifier consumption may be a new modifiable risk factor for colorectal cancer (CRC) and that alterations in host–microbiota interactions can favor gastrointestinal carcinogenesis in individuals with a genetical predisposition to such disorders.

scholarly journals Senescence under appraisal: hopes and challenges revisited

2021 ◽  
Author(s):  
Camilla S. A. Davan-Wetton ◽  
Emanuela Pessolano ◽  
Mauro Perretti ◽  
Trinidad Montero-Melendez
Keyword(s):  
Cellular Senescence ◽  
Clinical Success ◽  
Immune Surveillance ◽  
Favourable Outcome ◽  
Cellular Growth ◽  
Therapeutic Approaches ◽  
Cycle Arrest ◽  
Therapeutic Development ◽  
The Right ◽  
Inflammation Resolution

AbstractIn recent years, cellular senescence has become the focus of attention in multiple areas of biomedical research. Typically defined as an irreversible cell cycle arrest accompanied by increased cellular growth, metabolic activity and by a characteristic messaging secretome, cellular senescence can impact on multiple physiological and pathological processes such as wound healing, fibrosis, cancer and ageing. These unjustly called ‘zombie cells’ are indeed a rich source of opportunities for innovative therapeutic development. In this review, we collate the current understanding of the process of cellular senescence and its two-faced nature, i.e. beneficial/detrimental, and reason this duality is linked to contextual aspects. We propose the senescence programme as an endogenous pro-resolving mechanism that may lead to sustained inflammation and damage when dysregulated or when senescent cells are not cleared efficiently. This pro-resolving model reconciles the paradoxical two faces of senescence by emphasising that it is the unsuccessful completion of the programme, and not senescence itself, what leads to pathology. Thus, pro-senescence therapies under the right context, may favour inflammation resolution. We also review the evidence for the multiple therapeutic approaches under development based on senescence, including its induction, prevention, clearance and the use of senolytic and senomorphic drugs. In particular, we highlight the importance of the immune system in the favourable outcome of senescence and the implications of an inefficient immune surveillance in completion of the senescent cycle. Finally, we identify and discuss a number of challenges and existing gaps to encourage and stimulate further research in this exciting and unravelled field, with the hope of promoting and accelerating the clinical success of senescence-based therapies.

scholarly journals Codon harmonization reduces amino acid misincorporation in bacterially expressed P. falciparum proteins and improves their immunogenicity

AMB Express ◽  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Neeraja Punde ◽  
Jennifer Kooken ◽  
Dagmar Leary ◽  
Patricia M. Legler ◽  
Evelina Angov
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Codon Usage ◽  
Dna Sequences ◽  
Structural Integrity ◽  
Host Cells ◽  
Loss Of Function ◽  
Species Specific ◽  
And Function ◽  
The Impact

Abstract Codon usage frequency influences protein structure and function. The frequency with which codons are used potentially impacts primary, secondary and tertiary protein structure. Poor expression, loss of function, insolubility, or truncation can result from species-specific differences in codon usage. “Codon harmonization” more closely aligns native codon usage frequencies with those of the expression host particularly within putative inter-domain segments where slower rates of translation may play a role in protein folding. Heterologous expression of Plasmodium falciparum genes in Escherichia coli has been a challenge due to their AT-rich codon bias and the highly repetitive DNA sequences. Here, codon harmonization was applied to the malarial antigen, CelTOS (Cell-traversal protein for ookinetes and sporozoites). CelTOS is a highly conserved P. falciparum protein involved in cellular traversal through mosquito and vertebrate host cells. It reversibly refolds after thermal denaturation making it a desirable malarial vaccine candidate. Protein expressed in E. coli from a codon harmonized sequence of P. falciparum CelTOS (CH-PfCelTOS) was compared with protein expressed from the native codon sequence (N-PfCelTOS) to assess the impact of codon usage on protein expression levels, solubility, yield, stability, structural integrity, recognition with CelTOS-specific mAbs and immunogenicity in mice. While the translated proteins were expected to be identical, the translated products produced from the codon-harmonized sequence differed in helical content and showed a smaller distribution of polypeptides in mass spectra indicating lower heterogeneity of the codon harmonized version and fewer amino acid misincorporations. Substitutions of hydrophobic-to-hydrophobic amino acid were observed more commonly than any other. CH-PfCelTOS induced significantly higher antibody levels compared with N-PfCelTOS; however, no significant differences in either IFN-γ or IL-4 cellular responses were detected between the two antigens.

scholarly journals The Impact of Geography in Hepatocellular Carcinoma: A Retrospective Population Based Study

2021 ◽  
Vol 28 (1) ◽  
pp. 396-404
Author(s):  
Irene S. Yu ◽  
Shiru L. Liu ◽  
Valeriya Zaborska ◽  
Tyler Raycraft ◽  
Sharlene Gill ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retrospective Chart Review ◽  
Population Based ◽  
Tumor Board ◽  
Treatment Center ◽  
Population Based Study ◽  
Therapeutic Modalities ◽  
Quaternary Center ◽  
Statistics Canada ◽  
The Impact

Background: The treatment of hepatocellular carcinoma (HCC) includes different therapeutic modalities and multidisciplinary tumor board reviews. The impact of geography and treatment center type (quaternary vs. non-quaternary) on access to care is unclear. Methods: A retrospective chart review was performed on HCC patients who received sorafenib in British Columbia from 2008 to 2016. Patients were grouped by Statistics Canada population center (PC) size criteria: large PC (LPC), medium PC (MPC), and small PC (SPC). Access to specialists, receipt of liver-directed therapies, and survival outcomes were compared between the groups. Results: Of 286 patients, the geographical distribution was: LPC: 75%; MPC: 16%; and SPC: 9%. A higher proportion of Asians (51% vs. 9% vs. 4%; p < 0.001), Child–Pugh A (94% vs. 83% vs. 80%; p = 0.022), and hepatitis B (37% vs. 15% vs. 4%; p < 0.001) was observed in LPC vs. MPC vs. SPC, respectively. LPC patients were more likely referred to a hepatologist (62% vs. 48% vs. 40%; p = 0.031) and undergo transarterial chemoembolization (TACE) (43% vs. 24% vs. 24%; p = 0.018). Sixty percent were treated at a quaternary center, and the median overall survival (OS) was higher for patients treated at a quaternary vs. non-quaternary center (28.0 vs. 14.6 months, respectively; p < 0.001) but similar when compared by PC size. Treatment at a quaternary center predicted an improved survival on multivariate analysis (hazard ratio (HR): 0.652; 95% confidence interval (CI): 0.503–0.844; p = 0.001). Conclusions: Geography did not appear to impact OS but patients from LPC were more likely to be referred to hepatology and undergo TACE. Treatment at a quaternary center was associated with an improved survival.

scholarly journals Specialized Pro-Resolving Lipid Mediators in Neonatal Cardiovascular Physiology and Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 933
Author(s):  
Andrea Gila-Diaz ◽  
Gloria Herranz Carrillo ◽  
Pratibha Singh ◽  
David Ramiro-Cortijo
Keyword(s):  
Tissue Repair ◽  
Cardiovascular Health ◽  
Critical Role ◽  
Potential Effect ◽  
Lipid Mediators ◽  
Physiological Effects ◽  
Therapeutic Approaches ◽  
The Impact ◽  
Long Chain

Cardiovascular disease remains a leading cause of mortality worldwide. Unresolved inflammation plays a critical role in cardiovascular diseases development. Specialized Pro-Resolving Mediators (SPMs), derived from long chain polyunsaturated fatty acids (LCPUFAs), enhances the host defense, by resolving the inflammation and tissue repair. In addition, SPMs also have anti-inflammatory properties. These physiological effects depend on the availability of LCPUFAs precursors and cellular metabolic balance. Most of the studies have focused on the impact of SPMs in adult cardiovascular health and diseases. In this review, we discuss LCPUFAs metabolism, SPMs, and their potential effect on cardiovascular health and diseases primarily focusing in neonates. A better understanding of the role of these SPMs in cardiovascular health and diseases in neonates could lead to the development of novel therapeutic approaches in cardiovascular dysfunction.

scholarly journals Perturbation of host autophagy by the Irish potato famine pathogen

2014 ◽  
Vol 70 (a1) ◽  
pp. C826-C826
Author(s):  
Abbas Maqbool ◽  
Richard Richard ◽  
Tolga Bozkurt ◽  
Yasin Dagdas ◽  
Khaoula Belhai ◽  
...  
Keyword(s):  
Host Cell ◽  
Plant Cells ◽  
Irish Potato ◽  
Effector Proteins ◽  
Host Cells ◽  
Cell Physiology ◽  
Biochemical Basis ◽  
The Impact ◽  
Potato Famine ◽  
Irish Potato Famine

Autophagy is a catabolic process involving degradation of dysfunctional cytoplasmic components to ensure cellular survival under starvation conditions. The process involves formation of double-membrane vesicles called autophagosomes and delivery of the inner constituents to lytic compartments. It can also target invading pathogens, such as intracellular bacteria, for destruction and is thus implicated in innate immune pathways [1]. In response, certain mammalian pathogens deliver effector proteins into host cells that inhibit autophagy and contribute to enabling parasitic infection [2]. Pyhtophthora infestans, the Irish potato famine pathogen, is a causative agent of late blight disease in potato and tomato crops. It delivers a plethora of modular effector proteins into plant cells to promote infection. Once inside the cell, RXLR-type effector proteins engage with host cell proteins, to manipulate host cell physiology for the benefit of the pathogen. As plants lack an adaptive immune system, this provides a robust mechanism for pathogens to circumvent host defense. PexRD54 is an intracellular RXLR-type effector protein produced by P. infestans. PexRD54 interacts with potato homologues of autophagy protein ATG8 in plant cells. We have been investigating the structural and biochemical basis of the PexRD54/ATG8 interaction in vitro. We have purified PexRD54 and ATG8 independently and in complex from E. coli. Using protein/protein interaction studies we have shown that PexRD54 binds ATG8 with sub-micromolar affinity. We have also determined the structure of PexRD54 in the presence of ATG8. This crystal structure provides key insights into how the previously reported WY-fold of oomycete RXLR-type effectors [3] can be organized in multiple repeats. The structural data also provides insights into the interaction between PexRD54 and ATG8, suggesting further experiments to understand the impact of this interaction on host cell physiology and how this benefits the pathogen.

scholarly journals The Impact of Interferon Gamma Receptor Expression on the Mechanism of Escape From Host Immune Surveillance in Hepatocellular Carcinoma

Hepatology ◽  
2000 ◽  
Vol 32 (3) ◽  
pp. 491-500 ◽  
Author(s):  
Mitsuo Nagao ◽  
Yoshiyuki Nakajima ◽  
Hiromichi Kanehiro ◽  
Michiyoshi Hisanaga ◽  
Yukio Aomatsu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Interferon Gamma ◽  
Immune Surveillance ◽  
Receptor Expression ◽  
Gamma Receptor ◽  
The Impact ◽  
Host Immune Surveillance
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