A new approach to the treatment of acute infection diseases with antibiotic-pectin formulae.

INTRODUCTION: Intestinal infections are a significant health issue; antibiotics are essential in treating acute intestinal infections. However, evidence in the literature shows that the excessive use of antibiotics has created many threats to human health. This work aimed to study the impact of apple pectin in combination with antibiotics on treating patients with amebiasis and dysentery. METHODOLOGY: Patients suffering from acute intestinal diseases (amebiasis and dysentery) were treated with traditional antibiotic therapy and a new formula containing antibiotics with low and high methoxylated apple pectin in a randomized block design. Four clinical trials were performed at the Infection Disease Hospital from 1998 until 2013. RESULTS: The study demonstrated that the antibiotic-pectin formulae (APF) significantly reduced the severity of acute intestinal infection diseases and allowed patients to recover faster than conventional treatment. APF reduced the patient's stay in the hospital by 3.0 ± 1.0 days. The clinical trial findings demonstrated that applying APF in intestinal infection diseases helped maintain a constant concentration of the antibiotic in the blood and accelerated the clinical recovery of the patients. CONCLUSIONS: It was concluded that using pectin with antibiotics could improve clinical outcomes in patients with acute infectious diseases. Research on elucidating the mechanisms of pectin digestion in the colon, polyphenol content, and its role in dysbiosis recovery, etc., is also considered.

Oral Administration of Apple Pectin Solution Improves Atopic Dermatitis in a Mouse Model.

The development of atopic dermatitis (AD) involves multiple factors. Three such factors are particularly important in AD onset: immune abnormalities, skin barrier dysfunction, and itching. Many studies report that an imbalance between helper T (Th)1 and Th2 cells causes AD. Apple pectin, a prebiotic, has preventative effects in other allergic diseases (e.g., bronchial asthma and AD), but its potential benefits in AD are unclear. In this study, we investigated the effect of oral apple pectin administration on skin inflammation in an AD mouse model and examined changes in T cells involved in AD. To induce AD, a picryl chloride solution was applied to the shaved back skin of male NC/Nga mice. AD mice then received an oral apple pectin solution (0.4% or 4%) for 35 d. Compared with untreated AD mice, mice in both apple pectin-treated groups showed improvement in AD-induced inflammation and skin symptoms. Histological evaluation showed that apple pectin treatment attenuated epidermal thickening and decreased the number of mast cells and CD4+ cells in AD-induced mice. Apple pectin treatment also reduced serum IgE concentration, as well as expression of the inflammation indicator cyclooxygenase-2 and the Th2-related factors thymic stromal lymphopoietin, interleukin-4, and GATA3. Additionally, increased mRNA expression of the genes that encode interferon-γ and T-bet, which are Th1-related factors, and forkhead box protein P3, were observed in the apple pectin-treated groups. Our findings suggest that apple pectin treatment ameliorates AD by increasing regulatory T cells and improving the Th1/Th2 balance in the skin of AD model mice.

Evaluation of antimicrobial photodynamic action of a pluronic and pectin based film loaded with methylene blue against methicillin resistantStaphylococcus aureus.

Antimicrobial wound dressings play a crucial role in treatment of wound infections. However, existing commercial options fall short due to antibiotic resistance and the limited spectrum of activity of newly emerging antimicrobials against bacteria that are frequently encountered in wound infections. Antimicrobial photodynamic therapy (aPDT) is very promising alternative therapeutic approach against antibiotic resistant microbes such as methicillin resistantStaphylococcus aureus (MRSA). However, delivery of the photosensitizer (PS) homogeneously to the wound site is a challenge. Though polymeric wound dressings based on synthetic and biopolymers are being explored for aPDT, there is paucity of data regarding theirin vivoefficacy. Moreover, there are no studies on use of PS loaded, pluoronic (PL) and pectin (PC) based films for aPDT. We report development of a polymeric film for potential use in aPDT. The film was prepared using PL and PC via solvent casting approach and impregnated with methylene blue (MB) for photodynamic inactivation of MRSAin vitroandin vivo. Atomic force microscopic imaging of the films yielded vivid pictures of surface topography, with rough surfaces, pores, and furrows. The PL:PC ratio (2:3) was optimized that would result in an intact film but exhibit rapid release of MB in time scale suitable for aPDT. The film showed good antibacterial activity against planktonic suspension, biofilm of MRSA upon exposure to red light. Investigations on MRSA infected excisional wounds of mice reveal that topical application of MB loaded film for 30 min followed by red light exposure for 5 min (fluence; ∼30 J cm-2) or 10 min (fluence; ∼60 J cm-2) reduces ∼80% or ∼92% of bioburden, respectively. Importantly, the film elicits no significant cytotoxicity against keratinocytes and human adipose derived mesenchymal stem cells. Taken together, our data demonstrate that PS-loaded PL-PC based films are a promising new tool for treatment of MRSA infected wounds.

Modified pectin with anticancer activity in breast cancer: A systematic review.

Breast cancer is the most commonly diagnosed cancer among women worldwide. The current pharmacological treatments for breast cancer have numerous adverse effects and are not always effective. Recently, the anticancer activity of modified pectins (MPs) against various types of cancers, including breast cancer, has been investigated. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model, including scientific articles from the last 22 years that measured the anticancer activity of MPs on breast cancer. The articles were searched in four databases with the terms: "modified pectin" and "breast cancer". Nine articles were included, five in vitro and four mixed (in vitro and in vivo). Different models and methods by which anticancer activity was measured were analyzed. All the studies reported positive results in both cell lines and in vivo murine models of breast cancer. The extracted data suggest a positive effect and provide mechanistic evidence of MPs in the treatment of breast cancer. However, as limited number of studies were included, further in vivo studies are required to obtain more conclusive preclinical evidence.

Polysaccharides (pectin, mucilage, and fructan inulin) and their fermented products: A critical analysis of their biochemical, gut interactions, and biological functions as antidiabetic agents.

Diabetes mellitus is a globally metabolic endocrine syndrome marked by a deficiency of insulin secretion (type-1 DM) or glucose intolerance arising from insulin response impairment (type-2 DM) leading to abnormal glucose metabolism. With an increasing interest in natural dietary components for diabetes management, the identification of novel agents witnessed major discoveries. Plant-derived mucilage, pectin, and inulin are important non-starch polysaccharides that exhibit effective antidiabetic properties often termed soluble dietary fiber (SDF). SDF affects sugar metabolism through multiple mechanisms affecting glucose absorption and diffusion, modulation of carbohydrate metabolizing enzymes (α-amylase and α-glucosidase), ameliorating ß-pancreatic cell dysfunction, and improving insulin release or sensitivity. Certain SDFs inhibit dipeptidyl peptidase-4 and influence the expression levels of genes related to glucose metabolism. This review is designed to discuss holistically and critically the antidiabetic effects of major SDF and their underlying mechanisms of action. This review should aid drug discovery approaches in developing novel natural antidiabetic drugs from SDF.

Modified Citrus Pectin Treatment in Non-Metastatic Biochemically Relapsed Prostate Cancer: Long-Term Results of a Prospective Phase II Study.

The optimal therapy for patients with non-metastatic biochemically relapsed prostate cancer (BRPC-M0) after local therapy is elusive. Thus, the evaluation of new non-toxic compounds in BRPC-M0 patients is warranted. PectaSol®-Modified citrus pectin (P-MCP) is a food supplement categorized as GRAS (Generally Recognized As Safe) by the FDA. It is a competitive inhibitor of the galectin-3 protein, which is involved in cancer pathogenesis. In an early report of the present phase 2 study, P-MCP treatment for 6 months led to prostate-specific antigen doubling time (PSADT) improvement in 75% of patients with BRPC-M0. Herein, we report the second long-term treatment phase of an additional 12 months of P-MCP therapy (4.8 g × 3/day orally) in patients without disease progression after the initial 6 months of therapy. Of the 46 patients that entered the second treatment phase, 7 patients withdrew consent and decided to continue therapy out of pocket, and 39 initiated the second treatment phase. After a total of 18 months of P-MCP treatment, 85% (n = 33) had a durable long-term response, with 62% (n = 24) showing decreased/stable PSA, 90% (n = 35) PSADT improvement, and all with negative scans. No patient had grade 3/4 toxicity. In conclusion, P-MCP may have long-term durable efficacy and is safe in BRPC-M0.

Evaluation of citrus pectin capped copper sulfide nanoparticles against Candidiasis causing Candida biofilms.

The incidence of candidiasis has significantly increased globally in recent decades, and it is a significant source of morbidity and mortality, particularly in critically ill patients. Candida sp. ability to generate biofilms is one of its primary pathogenic traits. Drug-resistant strains have led to clinical failures of traditional antifungals, necessitating the development of a more modern therapy that can inhibit biofilm formation and enhance Candida sp. sensitivity to the immune system. The present study reports the anticandidal potential of pectin-capped copper sulfide nanoparticles (pCuS NPs) against Candida albicans. The pCuS NPs inhibit C. albicans growth at a minimum inhibitory concentration (MIC) of 31.25 µM and exhibit antifungal action by compromising membrane integrity and overproducing reactive oxygen species. The pCuS NPs, at their biofilm inhibitory concentration (BIC) of 15.63 µM, effectively inhibited C. albicans cells adhering to the glass slides, confirmed by light microscopy and scanning electron microscopy. Phase contrast microscopy pictures revealed that NPs controlled the morphological transitions between the yeast and hyphal forms by limiting conditions that led to filamentation and reducing hyphal extension. In addition, C. albicans showed reduced exopolysaccharide (EPS) production and exhibited less cell surface hydrophobicity (CSH) after pCuS NPs treatment. The findings suggest that pCuS NPs may be able to inhibit the emergence of virulence traits that lead to the formation of biofilms, such as EPS, CSH, and hyphal morphogenesis. The results raise the possibility of developing NPs-based therapies for C. albicans infections associated with biofilms.

Comparison of 10 and 14 days of antofloxacin-based versus 14 days of clarithromycin-based bismuth quadruple therapy for Helicobacter pylori eradication: A randomized trial.

OBJECTIVE: Our team previously reported the use of antofloxacin-based bismuth quadruple therapy for the eradication of Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of 10 and 14 days of antofloxacin-based versus 14 days of clarithromycin-based bismuth quadruple therapy in the first-line treatment for H. pylori infection. METHODS: 1174 patients with H. pylori infection were randomized into three groups: 10-days and 14-days antofloxacin (ANT10 and ANT14) groups who received 10 and 14 days of antofloxacin-based bismuth quadruple therapy (colloidal bismuth pectin 200 mg t.i.d., esomeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and antofloxacin 200 mg q.d.), 14-days clarithromycin (CLA14) group who received 14 days of clarithromycin-based bismuth quadruple therapy (colloidal bismuth pectin 200 mg t.i.d., esomeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.). Eradication rate, antibiotic resistance and adverse events were analyzed. RESULTS: The intention-to-treat (ITT) and per-protocol (PP) analyses have showed statistically different eradication rates between ANT14 group and ANT10 group (ITT p = 0.001; PP p < 0.001), but no statistical difference between ANT10 group and CLA14 group (ITT p = 0.340; PP p = 0.092). Treatment regimen, drug resistance and therapy duration were important clinical factors related to H. pylori eradication rates in multivariate logistic analysis. Longer durations had significantly higher eradication rates in patients with antibiotic-resistant strains or antibiotic-susceptible strains. The incidences of nausea and bitter taste were significantly higher in CLA group compared with ANT group (p = 0.002 for nausea; p = 0.002 for bitter taste). The ANT10 and ANT14 group had similar adverse event rates of gastrointestinal reactions. CONCLUSION: The study showed that the H. pylori eradication rate with ANT14 therapy was higher than that with ANT10 and CLA14 therapy without significantly increasing the rates of adverse event. 14 days of antofloxacin-based bismuth quadruple therapy may be a more effective way as the first-line treatment for H. pylori infection.

Pectin: A Bioactive Food Polysaccharide with Cancer Preventive Potential.

Pectin is an acidic heteropolysaccharide found in the cell walls and the primary and middle lamella of land plants. To be authorized as a food additive, industrial pectins must meet strict guidelines set forth by the Food and Agricultural Organization and must contain at least 65% polygalacturonic acid to achieve the E440 level. Fruit pectin derived from oranges or apples is commonly used in the food industry to gel or thicken foods and to stabilize acid-based milk beverages. It is a naturally occurring component and can be ingested by dietary consumption of fruit and vegetables. Preventing long-term chronic diseases like diabetes and heart disease is an important role of dietary carbohydrates. Colon and breast cancer are among the diseases for which data suggest that modified pectin (MP), specifically modified citrus pectin (MCP), has beneficial effects on the development and spread of malignancies, in addition to its benefits as a soluble dietary fiber. Cellular and animal studies and human clinical trials have provided corroborating data. Although pectin has many diverse functional qualities, this review focuses on various modifications used to develop MP and its benefits for cancer prevention, bioavailability, clinical trials, and toxicity studies. This review concludes that pectin has anti-cancer characteristics that have been found to inhibit tumor development and proliferation in a wide variety of cancer cells. Nevertheless, further clinical and basic research is required to confirm the chemopreventive or therapeutic role of specific dietary carbohydrate molecules.

Effects of pectins on colorectal cancer: targeting hallmarks as a support for future clinical trials.

The intake of dietary fibers has been associated with a reduction in the risk of colorectal cancer. Pectins - a class of dietary fibers - are polysaccharides that have a complex structure with a wide range of direct and indirect biological beneficial effects on humans. Direct effects include dilution of carcinogens, reduction in cholesterol levels, and interaction with immune cells. Indirect effects include the fermentation and production of short-chain fatty acids. All these biological effects have implications for colon cancer development; however, the exact mechanisms are not fully understood. In this review, we explore the clinical trials regarding dietary fibers and colorectal cancer, thus indicating the potential anti-cancer effects of pectins and modified pectins. We focused on the emerging biological effects of pectins through targeting colorectal cancer hallmark effects and the enabling characteristics. We provide an overview of the mechanisms for each hallmark capability and how the different pectins might exert that anti-cancer effect, such as induction of apoptosis, reduction in cancer cell proliferation and metastasis. The data compilation described herein can guide future clinical trials to investigate how to target specific pectin structures to act as an adjuvant in colon cancer treatment.

Effects of Quadruple Therapy Combined with Probiotics on Helicobacter Pylori-Related Peptic Ulcer.

The present study was designed to observe the effect of quadruple therapy combined with probiotics on Helicobacter pylori-related peptic ulcer. The patients in the control group (n = 90) were given regular quadruple therapy including proton pump inhibitor ilaprazole enteric-coated tablet + two antibiotics amoxicillin dispersible tablet and metronidazole tablet + colloidal bismuth pectin capsule for 2 weeks. Patients in the study group (n = 90) were given abovementioned quadruple therapy combined with probiotics live combined Bifidobacterium, Lactobacillus, and Enterococcus Capsules, oral for 2 weeks. Then Hp clearance rate, recurrence rate, levels of gastrointestinal hormone makers, and advance reactions between two groups were compared. At the 2nd week after the treatment, the Helicobacter pylori clearance rate in the study group (87.79%) was significantly higher than the control group (78.89%), and the total recurrence rate in the study group (6.67%) was significantly lower than the control group (13.33%) (P < 0.05). Serum gastrin and motilin expression were lower, and somatostatin expressions was significantly higher than those in the control group (P < 0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05). In summary, quadruple therapy combined with probiotics in the treatment of Helicobacter pylori-related peptic ulcer can improve the Helicobacter pylori clearance rate, reduce the Helicobacter pylori recurrence rate, and is beneficial to improving the level of gastrointestinal hormones, with certain safety.

Dual crosslinking of folic acid-modified pectin nanoparticles for enhanced oral insulin delivery.

Pectin-based drug delivery systems hold great potential for oral insulin delivery, since they possess excellent gelling property, good mucoadhesion and high stability in the gastrointestinal (GI) tract. However, lack of enterocyte targeting ability and premature drug release in the upper GI tract of the susceptible ionic-crosslinked pectin matrices are two major problems to be solved. To address these issues, we developed folic acid (FA)-modified pectin nanoparticles (INS/DFAN) as insulin delivery vehicles by a dual-crosslinking method using calcium ions and adipic dihydrazide (ADH) as crosslinkers. In vitro studies indicated insulin release behaviors of INS/DFAN depended on COOH/ADH molar ratio in the dual-crosslinking process. INS/DFAN effectively prevented premature insulin release in simulated GI fluids compared to ionic-crosslinked nanoparticles (INS/FAN). At an optimized COOH/ADH molar ratio, INS/DFAN with FA graft ratio of 18.2% exhibited a relatively small particle size, high encapsulation efficiency and excellent stability. Cellular uptake of INS/DFAN was FA graft ratio dependent when it was at/below 18.2%. Uptake mechanism and intestinal distribution studies demonstrated the enhanced insulin transepithelial transport by INS/DFAN via FA carrier-mediated transport pathway. In vivo studies revealed that orally-administered INS/DFAN produced a significant reduction in blood glucose levels and further improved insulin bioavailability in type I diabetic rats compared to INS/FAN. Taken together, the combination of dual crosslinking and FA modification is an effective strategy to develop pectin nano-vehicles for enhanced oral insulin delivery.

The Effect of Fiber Supplementation on Chronic Constipation in Adults: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Chronic constipation is a prevalent disorder that remains challenging to treat. Studies suggest increasing fiber intake may improve symptoms, although recommendations on the fiber type, dose, and treatment duration are unclear. OBJECTIVES: We investigated the effects of fiber supplementation on stool output, gut transit time, symptoms, and quality of life in adults with chronic constipation via a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: Studies were identified using electronic databases, backward citation, and hand searches of abstracts. RCTs reporting administration of fiber supplementation in adults with chronic constipation were included. Risks of bias (RoB) was assessed with the Cochrane RoB 2.0 tool. Results were synthesized using risk ratios (RRs), mean differences, or standardized mean differences (SMDs) and 95% CIs using a random-effects model. RESULTS: Sixteen RCTs with 1251 participants were included. Overall, 311 of 473 (66%) participants responded to fiber treatment and 134 of 329 (41%) responded to control treatment [RR: 1.48 (95% CI: 1.17, 1.88; P = 0.001); I2 = 57% (P = 0.007)], with psyllium and pectin having significant effects. A higher response to treatment was apparent in fiber groups compared to control groups irrespective of the treatment duration, but only with higher fiber doses (>10 g/d). Fiber increased stool frequency [SMD: 0.72 (95% CI: 0.36, 1.08; P = 0.0001); I2 = 86% (P < 0.00001)]; psyllium and pectin had significant effects, and improvement was apparent only with higher fiber doses and greater treatment durations (≥4 weeks). Fiber improved stool consistency (SMD: 0.32; 95% CI: 0.18, 0.46; P < 0.0001), particularly with higher fiber doses. Flatulence was higher in fiber groups compared to control groups(SMD: 0.80; 95% CI: 0.47, 1.13; P < 0.00001). CONCLUSIONS: Fiber supplementation is effective at improving constipation. Particularly, psyllium, doses >10 g/d and treatment durations of at least 4 weeks appear optimal, though caution is needed when interpreting the results due to considerable heterogeneity. These findings provide promising evidence on the optimal type and regime of fiber supplementation, which could be used to standardize recommendations to patients. The protocol for this review is registered at PROSPERO as CRD42020191404.

Impact of insufficient doses of medications on Helicobacter pylori eradication: a retrospective observational study.

BACKGROUND AND AIMS: The doses of medications may influence the success of Helicobacter pylori (H. pylori) eradication. This real-world observational study aimed to explore the impact of insufficient doses of medications prescribed for the bismuth-containing quadruple therapy (BQT) regimen on successful H. pylori eradication. METHODS: We retrospectively screened the patients who were diagnosed with H. pylori infection and received BQT regimens for H. pylori eradication at our department between January 2017 and July 2020. The rate of successful H. pylori eradication was compared according to the doses of medications prescribed. Standard doses were defined according to the clinical guidelines. RESULTS: Overall, 1054 patients were included. The rate of successful H. pylori eradication was 78.2% (824/1054). Among them, proton pump inhibitors (PPIs) and antibiotics were prescribed at insufficient doses in 37.0% (390/1054) and 6.7% (71/1054) of patients, respectively. Furthermore, pantoprazole (98.7% [385/390]) was the most common type of PPIs prescribed at insufficient doses, and nitroimidazoles (85.9% [61/71]) were the most common type of antibiotics prescribed at insufficient doses. Among the patients receiving colloidal bismuth pectin (CBP) (200 mg tid) and standard-dose antibiotics, the rate of successful H. pylori eradication was lower in insufficient-dose PPIs group than standard-dose PPIs group (78.1% [271/347] versus 82.6% [438/530], P = 0.095). Among the patients receiving CBP (200 mg tid) and standard-dose PPIs, the rate of successful H. pylori eradication was significantly lower in insufficient-dose antibiotics group than standard-dose antibiotics group (37.8% [14/37] versus 82.6% [438/530], P < 0.0001). Among the patients receiving CBP 200 mg tid, the rate of successful H. pylori eradication was significantly lower in patients receiving both PPIs and antibiotics at insufficient doses than those at standard doses (46.4% [13/28] versus 82.6% [438/530], P < 0.0001). CONCLUSION: Among the BQT regimens, PPIs and/or antibiotics, especially pantoprazole and metronidazole, are often prescribed at insufficient doses, compromising the success of H. pylori eradication. ABBREVIATIONS: H. pylori, Helicobacter pylori; UBT, urea breath test; DPM, disintegrations per minute; BQT, bismuth-containing quadruple therapy; PPI, proton pump inhibitor; CBP, colloidal bismuth pectin; qd, once daily; bid, twice daily; tid, three times daily; qid, four times daily.

Structural features and anticancer mechanisms of pectic polysaccharides: A review.

The anticancer activity of pectic polysaccharides (PPs) was proved by numerous studies, and which also indicated that the bioactivity of PPs was closely related to its complicated structures. Based on the summary and analysis about structure characteristics and corresponding enzymatic process of the reported PPs, the anticancer mechanism and related structural features were systematically clarified. It was found that not only the direct effects on the cancer cells by proliferation inhibition or apoptosis, but also the regulation of immune system, gut microbiota and gut metabolism as indirect effects, jointly played important roles in the anticancer of PPs. Nevertheless, during the study of PPs as promising anticancer components, the exact structure-function relationship, digestion process in vivo, and comprehensive action mechanism are still not well understanding. With the unveiling of the proposed issues, it is believed that PPs are promising to be exploited as effective cancer therapy/adjunctive therapy drugs or functional foods.

Characterization and prebiotic properties of pectin polysaccharide from Clausena lansium (Lour.) Skeels fruit.

Pectins have proven to be advantageous for human health as they regulate beneficial microbial communities and enhance immunity. The fruit of Clausena lansium (Lour.) Skeels (Wampee), also referred to as "treasure in fruit", is rich in pectin polysaccharides. In this study, a homogalacturonan-type pectin (CCP2) with a molecular weight of 8.9 × 104 Da and degree of esterification of 42.86% was isolated from Wampee fruit. The gut microbiota regulation and phagocytosis-enhancing properties of CCP2 were examined in vivo and in vitro, respectively. Oral administration of CCP2 dramatically decreased the abundance of Bacteroidetes and increased the abundance of Firmicutes in intestinal bacteria in mice. The content of short-chain fatty acids in the feces also significantly improved. Moreover, CCP2 exhibited excellent phagocytosis-enhancing activities on RAW 264.7 macrophages. These results suggested that CCP2 could be a potential gut microbiota regulator and phagocytosis-enhancer, which could be used in food products to promote health through beneficial manipulation of gut microbiota.

Modified Citrus Pectin Treatment in Non-Metastatic Biochemically Relapsed Prostate Cancer: Results of a Prospective Phase II Study.

Optimal therapy of biochemically relapsed prostate cancer (BRPC) after local treatment is elusive. An established modified citrus pectin (PectaSol®, P-MCP), a dietary polysaccharide, is an established antagonist of galectin-3, a carbohydrate-binding protein involved in cancer pathogenesis. Based on PSA dynamics, we report on the safety and the primary outcome analysis of a prospective phase II study of P-MCP in non-metastatic BRPC based. Sixty patients were enrolled, and one patient withdrew after a month. Patients (n = 59) were given P-MCP, 4.8 grams X 3/day, for six months. The primary endpoint was the rate without PSA progression and improved PSA doubling time (PSADT). Secondary endpoints were the rate without radiologic progression and toxicity. Patients that did not progress by PSA and radiologically at six months continued for an additional twelve months. After six months, 78% (n = 46) responded to therapy, with a decreased/stable PSA in 58% (n = 34), or improvement of PSADT in 75% (n = 44), and with negative scans, and entered the second twelve months treatment phase. Median PSADT improved significantly (p = 0.003). Disease progression during the first 6 months was noted in only 22% (n = 13), with PSA progression in 17% (n = 10), and PSA and radiologic progression in 5% (n = 3). No patients developed grade 3 or 4 toxicity.

The Dietary Intake of Carrot-Derived Rhamnogalacturonan-I Accelerates and Augments the Innate Immune and Anti-Viral Interferon Response to Rhinovirus Infection and Reduces Duration and Severity of Symptoms in Humans in a Randomized Trial.

Acute respiratory infections are an important health concern. Traditionally, polysaccharide-enriched extracts from plants, containing immunomodulatory rhamnogalacturonan-I (RG-1), were used prophylactically. We established the effects of dietary supplementation with carrot-derived RG-I (cRG-I, 0-0.3-1.5 g/day) in 177 healthy individuals (18-65 years) on symptoms following infection with rhinovirus strain 16 (RV16). Primary outcomes were changes in severity and duration of symptoms, and viral load in nasal lavage. Secondary outcomes were changes in innate immune and anti-viral responses, reflected by CXCL10 and CXCL8 levels and cell differentials in nasal lavage. In a nested cohort, exploratory transcriptome analysis was conducted on nasal epithelium. Intake of cRG-I was safe, well-tolerated and accelerated local cellular and humoral innate immune responses induced by RV16 infection, with the strongest effects at 1.5 g/d. At 0.3 g/d, a faster interferon-induced response, induction of the key anti-viral gene EIF2AK2, faster viral clearance, and reduced symptom severity (-20%) and duration (-25%) were observed. Anti-viral responses, viral clearance and symptom scores at 1.5 g/d were in between those of 0 and 0.3 g/d, suggesting a negative feedback loop preventing excessive interferon responses. Dietary intake of cRG-I accelerated innate immune and antiviral responses, and reduced symptoms of an acute respiratory viral infection.

Delineating the inherent functional descriptors and biofunctionalities of pectic polysaccharides.

Pectin is a plant-based heteropolysaccharide macromolecule predominantly found in the cell wall of plants. Pectin is commercially extracted from apple pomace, citrus peels and sugar beet pulp and is widely used in the food industry as a stabilizer, emulsifier, encapsulant, and gelling agent. This review highlights various parameters considered important for describing the inherent properties and biofunctionalities of pectins in food systems. These inherent descriptors include monosaccharide composition, galacturonic acid content, degree of esterification, molecular weight, structural morphology, functional group analysis, and functional properties, such as water and oil holding capacity, emulsification, foaming capacity, foam stability, and viscosity. In this study, we also delineate their potential as a nutraceutical, prebiotic, and carrier for bioactive compounds. The biofunctionalities of pectin as an anticancer, antioxidant, lipid-lowering, and antidiabetic agent are also conceptually elaborated in the current review. The multidimensional characteristics of pectin make it a potential candidate for use in food and biomedical science.

Enhancing clinical and immunological effects of anti-PD-1 with belapectin, a galectin-3 inhibitor.

BACKGROUND: PD-1/PD-L1 engagement and overexpression of galectin-3 (Gal-3) are critical mechanisms of tumor-induced immune suppression that contribute to immunotherapy resistance. We hypothesized that Gal-3 blockade with belapectin (GR-MD-02) plus anti-PD-1 (pembrolizumab) would enhance tumor response in patients with metastatic melanoma (MM) and head and neck squamous cell carcinoma (HNSCC). METHODS: We performed a phase I dose escalation study of belapectin+pembrolizumab in patients with advanced MM or HNSCC (NCT02575404). Belapectin was administered at 2, 4, or 8 mg/kg IV 60 min before pembrolizumab (200 mg IV every 3 weeks for five cycles). Responding patients continued pembrolizumab monotherapy for up to 17 cycles. Main eligibility requirements were a functional Eastern Cooperative Oncology Group status of 0-2, measurable or assessable disease, and no active autoimmune disease. Prior T-cell checkpoint antibody therapy was permitted. RESULTS: Objective response was observed in 50% of MM (7/14) and and 33% of HNSCC (2/6) patients. Belapectin+pembrolizumab was associated with fewer immune-mediated adverse events than anticipated with pembrolizumab monotherapy. There were no dose-limiting toxicities for belapectin within the dose range investigated. Significantly increased effector memory T-cell activation and reduced monocytic myeloid-derived suppressor cells (M-MDSCs) were observed in responders compared with non-responders. Increased baseline expression of Gal-3+ tumor cells and PD-1+CD8+ T cells in the periphery correlated with response as did higher serum trough levels of pembrolizumab. CONCLUSIONS: Belapectin+pembrolizumab therapy has activity in MM and HNSCC. Increased Gal-3 expression, expansion of effector memory T cells, and decreased M-MDSCs correlated with clinical response. Further investigation is planned.