Role of Respite Palliative Care in Understanding and Managing Complex Palliative Care Situation - A Case Report.

Introduction: The concept of total pain encompasses a person's physical, psychological, social, spiritual, and practical struggles. Effective pain and symptom management are the core elements of palliative care which aims at reducing suffering and improving quality of life (QOL) throughout the course of illness and need to be addressed with multidisciplinary coordinated approach in a timely manner. It may be challenging for palliative care providers to address all these distressing issues during short out-patient consultations. Hence, Respite Palliative Care Unit (RPCU) is an appropriate place to provide holistic patient care. Case Description: A 59-year-old widow, from Muslim community, was following up with Palliative Medicine out-patient department for management of progressively increasing chest pain with frequent exacerbations. She remained unsatisfied with the pain management and reported moderate to severe intensity of pain despite maximal pain management using multimodal approaches. We planned to systematically explore and address the issues leading to uncontrolled pain and distress. The patient was admitted to RPCU for holistic pain management and continuity of care. We explored and addressed the complex psycho-socio-spiritual aspects contributing to the total pain experience to achieve better symptom control and improve her overall well-being. Conclusion: This case report emphasizes the role of RPCU in effective and holistic management of psychosocial, spiritual issues, difficult communication, and advanced care planning. This model of palliative care can be a valuable addition to various health-care set-ups in the developing countries for improvement of patient care.

Synbiotic supplementation with prebiotic green banana resistant starch and probiotic Bacillus coagulans spores ameliorates gut inflammation in mouse model of inflammatory bowel diseases.

PURPOSE: The research goal is to develop dietary strategies to help address the growing incidence of inflammatory bowel diseases (IBD). This study has investigated the effectiveness of green banana resistant starch (GBRS) and probiotic Bacillus coagulans MTCC5856 spores for the amelioration of dextran-sulfate sodium (DSS)-induced colitis in mice. METHODS: Eight-week-old C57BL/6 mice were fed standard rodent chow diet supplemented with either B. coagulans, GBRS or its synbiotic combination. After 7 days supplementation, colitis was induced by adding 2% DSS in drinking water for 7 days while continuing the supplemented diets. Animal health was monitored and after 14 days all animals were sacrificed to measure the biochemical and histochemical changes associated with each supplement type. RESULTS: The disease activity index and histological damage score for DSS-control mice (6.1, 17.1, respectively) were significantly higher (p < 0.0001) than the healthy mice. Synbiotic supplementation alleviated these markers (- 67%, - 94% respectively) more adequately than B. coagulans (- 52%, - 58% respectively) or GBRS (- 57%, - 26%, respectively) alone. Compared to DSS-control synbiotic supplementation significantly (p < 0.0001) maintained expressions of tight junction proteins. Moreover, synbiotic effects accounted for ~ 40% suppression of IL-1ß and ~ 29% increase in IL-10 levels in serum while also reducing C-reactive protein (- 37%) compared to that of the DSS-control. While, B. coagulans alone could not induce additional levels of short-chain fatty acid (SCFA) production beyond the caecum, the synbiotic combination with GBRS resulted in substantial increased SCFA levels across the whole length of the colon. CONCLUSION: The synbiotic supplementation with B. coagulans and GBRS ameliorated the overall inflammatory status of the experimental IBD model via synergistic functioning. This supports researching its application in mitigating inflammation in human IBD.

Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory Mechanisms.

Oxidative stress is a key player of the inflammatory cascade responsible for the initiation of ulcerative colitis (UC). Although the short chain quinone idebenone is considered a potent antioxidant and a mitochondrial electron donor, emerging evidence suggests that idebenone also displays anti-inflammatory activity. This study evaluated the impact of idebenone in the widely used dextran sodium sulphate (DSS)-induced mouse model of acute colitis. Acute colitis was induced in C57BL/6J mice via continuous exposure to 2.5% DSS over 7 days. Idebenone was co-administered orally at a dose of 200 mg/kg body weight. Idebenone significantly prevented body weight loss and improved the disease activity index (DAI), colon length, and histopathological score. Consistent with its reported antioxidant function, idebenone significantly reduced the colonic levels of malondialdehyde (MDA) and nitric oxide (NO), and increased the expression of the redox factor NAD(P)H (nicotinamide adenine dinucleotide phosphate) dehydrogenase quinone-1 (NQO-1) in DSS-exposed mice. Immunohistochemistry revealed a significantly increased expression of tight junction proteins, which protect and maintain paracellular intestinal permeability. In support of an anti-inflammatory activity, idebenone significantly attenuated the elevated levels of pro-inflammatory cytokines in colon tissue. These results suggest that idebenone could represent a promising therapeutic strategy to interfere with disease pathology in UC by simultaneously inducing antioxidative and anti-inflammatory pathways.

A human origin strain Lactobacillus acidophilus DDS-1 exhibits superior in vitro probiotic efficacy in comparison to plant or dairy origin probiotics.

Background: The health benefits of probiotics are well established and known to be strain-specific. However, the role of probiotics obtained from different origins and their efficacy largely remains unexplored. The aim of this study is to investigate the in vitro efficacy of probiotics from different origins. Methods: Probiotic strains utilized in this study include Lactobacillus acidophilus DDS-1 (human origin), Bifidobacterium animalis ssp. lactis UABla-12 (human origin), L. plantarum UALp-05 (plant origin) and Streptococcus thermophilus UASt-09 (dairy origin). Screening assays such as in vitro digestion simulation, adhesion, cell viability and cytokine release were used to evaluate the probiotic potential. Results: All strains showed good resistance in the digestion simulation process, especially DDS-1 and UALp-05, which survived up to a range of 107 to 108 CFU/mL from an initial concentration of 109 CFU/mL. Two human colonic mucus-secreting cells, HT-29 and LS174T, were used to assess the adhesion capacity, cytotoxicity/viability, and cytokine quantification. All strains exhibited good adhesion capacity. No significant cellular cytotoxicity or loss in cell viability was observed. DDS-1 and UALp-05 significantly upregulated anti-inflammatory IL-10 and downregulated pro-inflammatory TNF-α cytokine production. All the strains were able to downregulate IL-8 cytokine levels. Conclusion: Of the 4 strains tested, DDS-1 demonstrated superior survival rates, good adhesion capacity and strong immunomodulatory effect under different experimental conditions.

Short-Chain Naphthoquinone Protects Against Both Acute and Spontaneous Chronic Murine Colitis by Alleviating Inflammatory Responses.

Ulcerative colitis (UC) is characterised by chronic, relapsing, idiopathic, and multifactorial colon inflammation. Recent evidence suggests that mitochondrial dysfunction plays a critical role in the onset and recurrence of this disease. Previous reports highlighted the potential of short-chain quinones (SCQs) for the treatment of mitochondrial dysfunction due to their reversible redox characteristics. We hypothesised that a recently described potent mitoprotective SCQ (UTA77) could ameliorate UC symptoms and pathology. In a dextran sodium sulphate- (DSS-) induced acute colitis model in C57BL/6J mice, UTA77 substantially improved DSS-induced body weight loss, disease activity index (DAI), colon length, and histopathology. UTA77 administration also significantly increased the expression of tight junction (TJ) proteins occludin and zona-occludin 1 (ZO-1), which preserved intestinal barrier integrity. Similar responses were observed in the spontaneous Winnie model of chronic colitis, where UTA77 significantly improved DAI, colon length, and histopathology. Furthermore, UTA77 potently suppressed elevated levels of proinflammatory cytokines and chemokines in colonic explants of both DSS-treated and Winnie mice. These results strongly suggest that UTA77 or its derivatives could be a promising novel therapeutic approach for the treatment of human UC.

Idebenone Protects against Spontaneous Chronic Murine Colitis by Alleviating Endoplasmic Reticulum Stress and Inflammatory Response.

Endoplasmic reticulum (ER) stress in intestinal secretory goblet cells has been linked to the development of ulcerative colitis (UC). Emerging evidence suggests that the short chain quinone drug idebenone displays anti-inflammatory activity in addition to its potent antioxidant and mitochondrial electron donor properties. This study evaluated the impact of idebenone in Winnie mice, that are characterized by spontaneous chronic intestinal inflammation and ER stress caused by a missense mutation in the mucin MUC2 gene. Idebenone (200 mg/kg) was orally administered daily to 5-6 weeks old Winnie mice over a period of 21 days. Idebenone treatment substantially improved body weight gain, disease activity index (DAI), colon length and histopathology score. Immunohistochemistry revealed increased expression of MUC2 protein in goblet cells, consistent with increased MUC2 mRNA levels. Furthermore, idebenone significantly reduced the expression of the ER stress markers C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6) and X-box binding protein-1 (XBP-1) at both mRNA and protein levels. Idebenone also effectively reduced pro-inflammatory cytokine levels in colonic explants. Taken together, these results indicate that idebenone could represent a potential therapeutic approach against human UC by its strong anti-inflammatory activity and its ability to reduce markers of ER stress.

Microbiota Modulating Nutritional Approaches to Countering the Effects of Viral Respiratory Infections Including SARS-CoV-2 through Promoting Metabolic and Immune Fitness with Probiotics and Plant Bioactives.

Viral respiratory infections (VRIs) can spread quickly and cause enormous morbidity and mortality worldwide. These events pose serious threats to public health due to time lags in developing vaccines to activate the acquired immune system. The high variability of people's symptomatic responses to viral infections, as illustrated in the current COVID-19 pandemic, indicates the potential to moderate the severity of morbidity from VRIs. Growing evidence supports roles for probiotic bacteria (PB) and prebiotic dietary fiber (DF) and other plant nutritional bioactives in modulating immune functions. While human studies help to understand the epidemiology and immunopathology of VRIs, the chaotic nature of viral transmissions makes it difficult to undertake mechanistic study where the pre-conditioning of the metabolic and immune system could be beneficial. However, recent experimental studies have significantly enhanced our understanding of how PB and DF, along with plant bioactives, can significantly modulate innate and acquired immunity responses to VRIs. Synbiotic combinations of PB and DF potentiate increased benefits primarily through augmenting the production of short-chain fatty acids (SCFAs) such as butyrate. These and specific plant polyphenolics help to regulate immune responses to both restrain VRIs and temper the neutrophil response that can lead to acute respiratory distress syndrome (ARDS). This review highlights the current understanding of the potential impact of targeted nutritional strategies in setting a balanced immune tone for viral clearance and reinforcing homeostasis. This knowledge may guide the development of public health tactics and the application of functional foods with PB and DF components as a nutritional approach to support countering VRI morbidity.

Modulating the Microbiome and Immune Responses Using Whole Plant Fibre in Synbiotic Combination with Fibre-Digesting Probiotic Attenuates Chronic Colonic Inflammation in Spontaneous Colitic Mice Model of IBD.

A probiotic and prebiotic food ingredient combination was tested for synergistic functioning in modulation of the colonic microbiome and remediation of the gastrointestinal immune and inflammatory responses in a spontaneous colitic mouse model. Bacillus coagulans MTCC5856 spores with capability to metabolise complex plant polysaccharides were supplemented with complex whole-plant prebiotic sugarcane fibre (PSCF). The combined and individual efficacies were tested for their influence on the outcomes of chronic inflammation in Muc2 mutant colitic Winnie mice. The mice were fed normal chow diet supplemented with either ingredient or a combination for 21 days. Synbiotic combined supplementation ameliorated clinical symptoms and histological colonic damage scores more effectively than either B. coagulans or PSCF alone. PSCF and B. coagulans alone also induced considerable immunomodulatory effects. Synbiotic supplementation however was the most efficacious in modulating the overall immune profile compared to the unsupplemented Winnie-control. The augmented synbiotic effect could potentially be due to a combination of increased levels of fermentation products, direct immune-modulating abilities of the components, their capability to reduce colonic epithelial damage and/or modulation of the microbiota. The beneficial effects of the supplementation with a complex plant fibre and a fibre-degrading probiotic parallel the effects seen in human microbiota with high plant fibre diets.

Synbiotic Supplementation Containing Whole Plant Sugar Cane Fibre and Probiotic Spores Potentiates Protective Synergistic Effects in Mouse Model of IBD.

Inflammatory bowel diseases (IBD) are a chronic inflammatory disorders with increasing global incidence. Synbiotic, which is a two-point approach carrying probiotic and prebiotic components in mitigating inflammation in IBD, is thought to be a pragmatic approach owing to the synergistic outcomes. In this study, the impacts of dietary supplementation with probiotic Bacillus coagulans MTCC5856 spores (B. coagulans) and prebiotic whole plant sugar cane fibre (PSCF) was assessed using a murine model of IBD. Eight-week-old C57BL/6 mice were fed a normal chow diet supplemented with either B. coagulans, PSCF or its synbiotic combination. After seven days of supplementation, colitis was induced with dextran sulfate sodium (DSS) in drinking water for seven days during the continuation of the supplemented diets. Synbiotic supplementation ameliorated disease activity index and histological score (-72%, 7.38, respectively), more effectively than either B. coagulans (-47%, 10.1) and PSCF (-53%, 13.0) alone. Synbiotic supplementation also significantly (p < 0.0001) prevented the expression of tight junction proteins and modulated the altered serum IL-1ß (-40%), IL-10 (+26%), and C-reactive protein (CRP) (-39%) levels. Synbiotic supplementations also raised the short-chain fatty acids (SCFA) profile more extensively compared to the unsupplemented DSS-control. The synbiotic health outcome effect of the probiotic and prebiotic combinations may be associated with a synergistic direct immune-regulating efficacy of the components, their ability to protect epithelial integrity, stimulation of probiotic spores by the prebiotic fibre, and/or with stimulation of greater levels of fermentation of fibres releasing SCFAs that mediate the reduction in colonic inflammation. Our model findings suggest synbiotic supplementation should be tested in clinical trials.

Lactobacillus acidophilus DDS-1 Modulates Intestinal-Specific Microbiota, Short-Chain Fatty Acid and Immunological Profiles in Aging Mice.

Distribution of the microbiota varies according to the location in the gastrointestinal (GI) tract. Thus, dysbiosis during aging may not be limited to faecal microbiota and extend to the other parts of the GI tract, especially the cecum and colon. Lactobacillus acidophilus DDS-1, a probiotic strain, has been shown to modulate faecal microbiota and its associated metabolic phenotype in aging mice. In the present study, we investigated the effect of L. acidophilus DDS-1 supplementation on caecal- and mucosal-associated microbiota, short-chain fatty acids (SCFAs) and immunological profiles in young and aging C57BL/6J mice. Besides differences in the young and aging control groups, we observed microbial shifts in caecal and mucosal samples, leading to an alteration in SCFA levels and immune response. DDS-1 treatment increased the abundances of beneficial bacteria such as Akkermansia spp. and Lactobacillus spp. more effectively in caecal samples than in mucosal samples. DDS-1 also enhanced the levels of butyrate, while downregulating the production of inflammatory cytokines (IL-6, IL-1ß, IL-1α, MCP-1, MIP-1α, MIP-1ß, IL-12 and IFN-γ) in serum and colonic explants. Our findings suggest distinct patterns of intestinal microbiota, improvements in SCFA and immunological profiles with DDS-1 supplementation in aging mice.

Lactobacillus acidophilus DDS-1 Modulates the Gut Microbiota and Improves Metabolic Profiles in Aging Mice.

Recent evidence suggests that gut microbiota shifts can alter host metabolism even during healthy aging. Lactobacillus acidophilus DDS-1, a probiotic strain, has shown promising probiotic character in vitro, as well as in clinical studies. The present study was carried out to investigate whether DDS-1 can modulate the host metabolic phenotype under the condition of age-affected gut microbial shifts in young and aging C57BL/6J mice. Collected fecal samples were analyzed using 16S rRNA gene sequencing for identifying gut microbiota and untargeted gas chromatography-mass spectrometry (GC-MS) metabolomics analysis. Gut microbial shifts were observed in the control groups (young and aging), leading to an alteration in metabolism. Principal coordinate analysis (PCoA) of microbiota indicated distinct separation in both the DDS-1-treated groups. L. acidophilus DDS-1 increased the relative abundances of beneficial bacteria, such as Akkermansia muciniphila and Lactobacillus spp., and reduced the relative levels of opportunistic bacteria such as Proteobacteria spp. Metabolic pathway analysis identified 10 key pathways involving amino acid metabolism, protein synthesis and metabolism, carbohydrate metabolism, and butanoate metabolism. These findings suggest that modulation of gut microbiota by DDS-1 results in improvement of metabolic phenotype in the aging mice.

MCC950, a specific small molecule inhibitor of NLRP3 inflammasome attenuates colonic inflammation in spontaneous colitis mice.

MCC950 a potent, highly specific small molecule inhibitor of canonical and noncanonical activation of NLRP3 inflammasome has been evaluated in a multitude of NLRP3 driven inflammatory diseases. However, the effect of MCC950 on colonic inflammation has not yet been reported. In the present study we investigated the effect of MCC950 in a spontaneous chronic colitis mouse model Winnie, which mimics human ulcerative colitis. Oral administration of 40 mg/kg MCC950 commencing at Winnie week seven for three weeks significantly improved body weight gain, colon length, colon weight to body weight ratio, disease activity index and histopathological scores. MCC950 significantly suppressed release of proinflammatory cytokines IL-1ß, IL-18, IL1-α, IFNγ, TNF-α, IL6, IL17, chemokine MIP1a and Nitric Oxide in colonic explants. Moreover, MCC950 resulted in a significant decrease of IL-1ß release and activation of caspase-1 in colonic explants and macrophage cells isolated from Winnie. Complete inhibition with MCC950 in Winnie colonic explants shows, for the first time, the contribution of inflammatory effects resulting exclusively from canonical and noncanonical NLRP3 inflammasome activation in colitis. Taken together, our results illustrate the efficacy of MCC950 in the treatment of murine ulcerative colitis and provides avenue for a potential novel therapeutic agent for human inflammatory bowel diseases.