Arthritis

Abstract

Objectives:  RA develops slowly over years. We tested for metabolic changes prior to RA onset using a large non-targeted metabolomics platform to identify novel pathways and advance understanding of RA development.

Methods: Two hundred and fifty-four incident RA cases with plasma samples drawn pre-RA onset in the Nurses' Health Study (NHS) cohorts were matched 1:2 to 501 controls on age, race, menopause/post-menopausal hormone use and blood collection features. Relative abundances of 360 unique, known metabolites were measured. Conditional logistic regression analyses assessed associations between metabolites and incidence of RA, adjusted for age, smoking and BMI, accounting for multiple comparisons. Subgroup analyses investigated seropositive (sero+) RA and RA within 5 years of sample collection. Significant metabolites were then tested in a female military pre-RA case-control study (n = 290).

Abstract

Objective: Changes in polyamine-modulated factor 1 (PMF-1) promoter methylation might favor the expression of spermidine/spermine N1-acetyltransferase 1 (SSAT-1), causing excessive consumption of S-adenosyl methionine (SAM). This study was undertaken to evaluate the effect of SSAT-1 activity inhibition, either alone or in combination with SAM.

Methods:  Synovial fibroblasts were isolated from patients with rheumatoid arthritis (RA) or osteoarthritis (OA). PMF-1 promoter methylation was determined by pyrosequencing. Small interfering RNAs (siRNAs) against SSAT-1 were transfected weekly in RA synovial fibroblasts (RASFs). In addition, synovial fibroblasts were treated with diminazene aceturate (DA), an inhibitor of SSAT-1. SSAT-1, 5-methylcytosine (5-MeC), adenosyl methionine decarboxylase (AMD), PMF-1, DNA methyltransferase 1 (DNMT-1), CXCL12, β1 integrin, and CD44 levels were measured by flow cytometry. Putrescine levels were determined by colorimetry. Levels of matrix metalloproteinases were measured by enzyme-linked immunosorbent assay. Cell adhesion was tested. The SCID mouse model of RA was used to monitor the invasiveness of RASFs.

Abstract

Combination of Aconiti Lateralis Radix Praeparata (FZ) and Paeoniae Radix Alba (BS) shows a significant effect in rheumatoid arthritis (RA). This study aimed to investigate the efficacy enhancing and toxicity reducing mechanism of combination of them in adjuvant-induced arthritis (AIA) rats by metabolomics. Rats were randomly divided into seven groups, including A (healthy control), B (model control), C1 (therapy group), C2 (efficacy enhancing group), D1 (toxicity group), and D2 (toxicity reducing group), and dexamethasone group was used as positive control. The plasma biochemical indexes showed that therapeutic dose of lipid-soluble alkaloids of FZ could significantly inhibit the concentrations of IL-1β, TNF-α, and IFN-γ in AIA rats, and combination with total glucosides of peony could further reduce the concentration of IL-1β. Then, UPLC-LTQ/Orbitrap MS with untargeted metabolomics was performed to identify the possible metabolites and pathways. Through multivariate data analysis of therapeutic dose groups (A vs. B vs. C1 vs. C2) and multivariate data analysis of toxic dose groups (A vs. B vs. D1 vs. D2), 10 and 7 biomarkers were identified based on biomarker analysis, respectively. After inducing AIA model, the plasma contents of spermidine, vanillylmandelic acid, catechol, and linoleate were increased significantly, and the contents of citric acid, L-tyrosine, L-phenylalanine, leucine, L-tryptophan, and uridine 5'-monophosphate (UMP) were decreased significantly.

Abstract

Ageing is the primary risk factor for osteoarthritis (OA). A decline in the ageing-associated process of autophagy is suggested as a potential contributor to OA development. Polyamines such as spermidine decrease during ageing, contributing to impaired autophagy and reduced cellular function. However, the role of polyamines and their effect on the regulatory mechanism governing autophagy in aged and arthritic cartilage tissue has not been established. Elucidating if polyamine regulation of autophagy is impaired during ageing and OA in chondrocytes may lead to improved treatment approaches to protect against cartilage degradation. Our results indicate that polyamine synthesis was decreased in aged and OA cartilage, along with reduced autophagy activity, evidenced by decreased autophagy-related gene and protein expression and autophagosome formation. Importantly, spermidine treatment increased the expression of the acetyltransferase EP300, which binds to crucial autophagy proteins, Beclin1 and LC3, and elevates chondrocyte autophagy. Our data indicate spermidine prevents the ageing- and OA-related decrease in autophagy and may protect against OA development.

Objective: The fermented wheat germ extract (FWGE) nutraceutical (FWGE™), manufactured under “good manufacturing practice” conditions and, fulfilling the self-affirmed “generally recognized as safe” status in the United States, has been approved as a “dietary food for special medical purposes for cancer patients” in Europe. In this paper, we report the adjuvant use of this nutraceutical in the treatment of high-risk skin melanoma patients. Methods: In a randomized, pilot, phase II clinical trial, the efficacy of dacarbazine (DTIC)-based adjuvant chemotherapy on survival parameters of melanoma patients was compared to that of the same treatment supplemented with a 1-year long administration of FWGE. Results: At the end of an additional 7-year-long follow-up period, log-rank analyses (Kaplan-Meier estimates) showed significant differences in both progression-free (PFS) and overall survival (OS) in favor of the FWGE group. Mean PFS: 55.8 months (FWGE group) versus 29.9 months (control group), p 0.0137. Mean OS: 66.2 months (FWGE group) versus 44.7 months (control group), p 0.0298. Conclusions: The inclusion of FWGE into the adjuvant protocols of high-risk skin melanoma patients is highly recommended.

Background and aim Anorexia/cachexia syndrome is frequently correlated with increased oxidative stress (OS). A fermented wheat-germ extract with a standardized benzoquinone content (brand name FWGE) has been shown to exert an intense antioxidant activity with no side effects. The aim of this study was to investigate the effects of FWGE in patients affected by head and neck cancer, correlating the variations with OS with the quality of life as assessed by the Spitzer’s index. Patients and methods A cohort of 60 patients affected by head and neck tumours (stage IIIa, IIIb, IV) were enrolled in the study following an open-label protocol. The patients were assigned to two subgroups, A or B. Group A was treated with conventional oncological therapy alone, and group B was treated with FWGE in addition to standard therapy. After 2 months only 55 patients survived and could be evaluated (29 in the control group and 26 in the FWGE group). Each patient was checked for circulating concentrations of hydroperoxides using the FRAS III test. Results The levels of OS significantly decreased after 2 months in the group receiving FWGE (group). The value of Spitzer’s index was significantly higher in group B, attesting to an improved quality of life. Conclusion Although the specific active substance in FWGE has not yet been identified, the reduction in free oxygen radicals induced by it is correlated with a clinically significant improvement in the quality of life in patients with advanced cancer. 

The Hungarian Association of Oral and Maxillofacial Surgeons (Magyar Arc-, Állcsont- és Szájsebészeti Társaság) has reviewed the research results related to FWGE and issued its opinion as follows: For patients suffering from head- and neck tumors - primarily malignant tumorous diseases of the oral cavity, the progression of the disease can be slowed significantly, the five-year survival rate increased considerably, the quality of life improved, and the oxidative stress on the patients reduced by the long-term application of the supplementary formula FWGE . The Association considers the supportive treatment with the formula FWGE as an important part of the complex therapeutic protocols applied in stages II, III and IV of malignant tumorous diseases of the oral cavity. 

Objective. To investigate the effect of the fermented wheat germ extract (FWGE ®) in patients with severe rheumatoid arthritis (RA). Methods. Fifteen female RA (Steinbrocker II-III) patients, who had unsuccesfully tried two different DMARD treatments, were enrolled in an open-label, 1-year long, pilot clinical study. DMARD and steroid therapies were recorded and continued. All patients received FWGE ® as additional therapy. For measurement of efficacy the Ritchie Index, the Health Assessment Questionnaire (HAQ) and the assessment of morning stiffness were applied. Patients were evaluated at baseline, 6 and 12 months. For statistical analyses the Wilcoxon test was used. Results. At both 6 and 12 months, Ritchie index, HAQ and morning stiffness showed significant improvements compared with the baseline values. Dosages of steroids could be reduced in about half of the patients. No side effects of FWGE ® were observed. Conclusion. Supplementation of standard therapies with a continuous administration of FWGE ® is beneficial for RA patients.

The hypothesis that oxidative stress favours flogistic and immune processes inducing autoimmune rheumatic diseases (ARDs) and their complications is still under discussion. In this review we take into consideration both the aetiopathological role of the diet in such diseases and the possible efficacy of dietary supports as adjuvants for the usual specific therapies. Moreover, we shall examine the hypothetical pathophysiological role of oxidative stress on ARDs and their complications, the methods for its evaluation and the possibility of intervening on oxidative pathways by means of nutritional modulation. It is possible that in the future we will be able to control connective pathology by associating an immuno-modulating therapy (‘re-educating’) with naturalproducts having an anti-oxidant activity to current immunosuppressive treatment (which has potentially toxic effects).
2003 Elsevier B.V. All rights reserved.

Purpose: An open-label, matched-pair (by diagnosis, stage of disease, age, and gender) pilot clinical trial was conducted to test whether the combined administration of the medical nutriment MSC (FWGE ) with cytotoxic drugs and the continued administration of MSC on its own help to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers compared with the same treatments without MSC. Methods: Between December 1998 and May 2002, 22 patients (11 pairs) were enrolled in this study. At baseline, the staging of the tumors was the same in each pair (mostly pTNM = T2N0M0), with the exception of two cases in which patients in the MSC group had worse prognoses (metastasis at baseline). There were no significant differences in the average age of the patients, the length of treatment time (MSC) or follow-up, the number of patients with central venous catheters, the number of chemotherapy cycles, the frequency of preventive counterneutropenic interventions, or the type and dosage of antibiotic and antipyretic therapy used in the two groups. Results: During the treatment (follow-up) period, there was no progression of the malignant disease, whereas at end-point the number and frequency of febrile neutropenic events significantly differed between the two groups: 30 febrile neutropenic episodes (24.8%) in the MSC group versus 46 (43.4%) in the control group (Wilcoxon signed rank test, P < 0.05). Conclusions: The continuous supplementation of anticancer therapies with the medical nutriment MSC helps to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers.

MSC (FWGE) is a medical nutriment of which preclinical and observational clinical studies suggested an antimetastatic activity with no toxicity. This open-label cohort trial has compared anticancer treatments plus MSC (9 g once daily) vs anticancer treatments alone in colorectal patients, enrolled from three oncosurgical centres; cohort allocation was on the basis of patients’ choice. Sixty-six colorectal cancer patients received MSC supplement for more than 6 months and 104 patients served as controls (anticancer therapies alone): no statistical difference was noted in the time from diagnosis to the last visit between the two groups. End-point analysis revealed that progression-related events were significantly less frequent in the MSC group (new recurrences: 3.0 vs 17.3%, Po0.01; new metastases: 7.6 vs 23.1%, Po0.01; deaths: 12.1 vs 31.7%, Po0.01). Survival analysis showed significant improvements in the MSC group regarding progression-free (P ¼ 0.0184) and overall survivals (P ¼ 0.0278) probabilities. Survival predictors in Cox’s proportional hazards were UICC stage and MSC treatment. Continuous supplementation of anticancer therapies with MSC for more than 6 months is beneficial to patients with colorectal cancer in terms of overall and progression-free survival. 

FWGE pulvis” is a powder consisting of an aqueous extract of fermented wheat germ, with the drying aids maltodextrin and silicon dioxide, standardized to contain approximately 200 µg/g of the natural constituent 2,6-dimethoxy-p-benzoquinone. The results of toxicological and clinical studies of this product demonstrate its safety for its intended use as a dietary supplement ingredient in the United States. FWGE pulvis has been used in Hungary since 1998 and is approved in that country, as well as in the Czech Republic, Bulgaria, and Romania, as a “medical nutriment for cancer patients.” Acute and subacute toxicity studies using rodents orally administered FWGE pulvis showed that dose levels (2000 to 3000 mg/kg body weight [bw]/day) exceeding the normal recommended oral dosage (8.5 g/day or 121 mg/kg bw/day for a 70-kg individual) by up to approximately 25-fold caused no adverse effects. The test substance showed no evidence of mutagenicity or genotoxicity in vitro or in vivo. Clinical studies using FWGE pulvis as a supplement to drug therapy in cancer patients at doses of 8.5 g/day not only showed no evidence of toxicity, but also showed a reduction in the side effects of chemotherapy. Overall, it was concluded that FWGE pulvis would not be expected to cause adverse effects under the conditions of its intended use as an ingredient in dietary supplements.

ACCREDITATION InnoVision Communications is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. CREDIT DESIGNATION STATEMENT InnoVision Communications designates this educational activity for a maximum of 1.5 AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the extent of their participation in the activity. STATEMENT OF PURPOSE Natural products are being used as supplements by cancer patients, with or without the knowledge of their cancer treatment team. It is important to know which of these products show efficacy against diseases such as cancer, and which are ineffective. It is also essential to define the mechanism(s) of action of natural products, especially as relevant to cancer prevention or treatment. The purpose of this article is to review the use of one such natural product, a fermented wheat germ extract (FWGE ), in the treatment regimen of cancer patients. FWGE has shown efficacy in both animal cancer models and human clinical trials with cancer patients, but more well-controlled trials in humans are necessary to assess the full potential of FWGE in cancer treatment. FWGE exerts its anticancer effect via an array of mechanisms, likely because there are many undefined components in this product that modulate numerous biological systems in cancer patients. 

In this study, the protective effect of a fermented wheat germ extract (FWGE) against LPS-induced inflammation and oxidative stress in IPEC-J2 porcine intestinal epithelial cells was studied. Enterocytes were treated with LPS derived from Salmonella enterica ser. Typhimurium and Escherichia coli O55:B5, O111:B4, and O127:B8 strains. Intracellular ROS level and extracellular H2O2 level were followed up by two fluorescent assays (DCFH-DA and Amplex Red). The effect of FWGE on the intestinal barrier integrity was determined by transepithelial electric resistance measurements and using a FD4 fluorescent tracer dye. IL-6 concentration of supernatants was also measured by the ELISA method. Our data revealed that FWGE had a significant lowering effect on the inflammatory response especially related to oxidative stress. Treatment with FWGE (1-2%) significantly decreased the level of intracellular ROS compared to LPS-treated cells. Furthermore, LPS-triggered partial disruption of epithelial integrity was reduced after FWGE application.

Abstract--The acute and subacute toxicity of five biogenic amines--tyramine, spermidine, spermine, putrescine and cadaverine--were examined in Wistar rats. Tyramine and cadaverine had a low acute oral toxicity of more than 2000 mg/kg body weight. Putrescine had an acute oral toxicity of 2000 mg/kg body weight and spermidine and spermine each of 600 mg/kg body weight. All amines investigated caused a dose-related decrease in blood pressure after intravenous administration, except for tyramine, where an increase was h~und. In 6-wk studies the biogenic amines were administered in the diet to groups of 10 male and 10 female rats. Tyramine and cadaverine were given at levels of 0, 200, 2000 or 10,000 ppm, spermine and putrescine at levels of 0, 200, 2000 or 5000 ppm and spermidine at levels of 0, 20, 200 or 500/1000 ppm in the first study and at levels of 0 or 10,000 ppm in a second study. Spermine was the most toxic. The high dose level showed a great number of changes, such as emaciation, aggressiveness, convulsions and paralysis of the hind legs. Growth, food intake and water intake were considerably decreased. Slight anaemia (males) and changes in plasma clinical chemistry occurred. The relative weights of the thyroid, adrenals, spleen and heart were increased and that of the liver decreased. Impaired kidney function, together with renal histopathological changes and changes in plasma electrolytes and urea, occurred with ,;permine. Histopathological examinations also revealed decreased glycogen content in the liver, reduction of spermatogenesis, severe depletion of splenic white pulp, acute involution of the thymus and moderate myocardial degeneration in the heart. 

Supplementation of spermidine, an autophagy‐inducing agent, has been shown to protect against neurodegeneration and cognitive decline in aged animal models. The present translational study aimed to determine safety and tolerability of a wheat germ extract containing enhanced spermidine concentrations. In a preclinical toxicity study, supplementation of spermidine using this extract did not result in morbidities or changes in behavior in BALBc/Rj mice during the 28‐days repeated‐dose tolerance study. Post mortem examination of the mice organs showed no increase in tumorigenic and fibrotic events. In the human cohort (participants with subjective cognitive decline, n=30, 60 to 80 years of age), a 3‐month randomized, placebo‐ controlled, double‐blind Phase II trial was conducted with supplementation of the spermidine‐rich plant extract (dosage: 1.2 mg/day). No differences were observed between spermidine and placebo‐treated groups in vital signs, weight, clinical chemistry and hematological parameters of safety, as well as in self‐reported health status at the end of intervention. Compliance rates above 85% indicated excellent tolerability. The data demonstrate that spermidine supplementation using a spermidine‐rich plant extract is safe and well‐tolerated in mice and older adults. These findings allow for longer‐term intervention studies in humans to investigate the impact of spermidine treatment on cognition and brain integrity.

FWGE pulvis” is a powder consisting of an aqueous extract of fermented wheat germ, with the drying aids maltodextrin and silicon dioxide, standardized to contain approximately 200 µg/g of the natural constituent 2,6-dimethoxy-p-benzoquinone. The results of toxicological and clinical studies of this product demonstrate its safety for its intended use as a dietary supplement ingredient in the United States. FWGE pulvis has been used in Hungary since 1998 and is approved in that country, as well as in the Czech Republic, Bulgaria, and Romania, as a “medical nutriment for cancer patients.” Acute and subacute toxicity studies using rodents orally administered FWGE pulvis showed that dose levels (2000 to 3000 mg/kg body weight [bw]/day) exceeding the normal recommended oral dosage (8.5 g/day or 121 mg/kg bw/day for a 70-kg individual) by up to approximately 25-fold caused no adverse effects. The test substance showed no evidence of mutagenicity or genotoxicity in vitro or in vivo. Clinical studies using FWGE pulvis as a supplement to drug therapy in cancer patients at doses of 8.5 g/day not only showed no evidence of toxicity, but also showed a reduction in the side effects of chemotherapy. Overall, it was concluded that FWGE pulvis would not be expected to cause adverse effects under the conditions of its intended use as an ingredient in dietary supplements.

abstract

 2,6-Dimethoxy-1,4-benzoquinone (2,6-DMBQ) is the major bioactive compound found in fermented

wheat germ extract. Although fermented wheat germ extract has been reported to show antiproliferative and anti-metabolic effects in various cancers, the anticancer potential and molecular

mechanisms exerted by 2,6-DMBQ have not been investigated in non-small cell lung cancer (NSCLC)

cells. Here, we report that 2,6-DMBQ suppresses NSCLC cell growth and migration through inhibiting

activation of AKT and p38 MAPK. 2,6-DMBQ significantly suppressed anchorage-dependent and independent cell growth. Additionally, 2,6-DMBQ induced G2 phase cell cycle arrest through inhibiting the

expression and phosphorylation of cyclin B1 and CDC2, respectively. Furthermore, 2,6-DMBQ strongly

suppressed NSCLC cell migration through induction of E-cadherin expression. To determine the molecular mechanism(s) exerted by 2,6-DMBQ upon NSCLC cell lines, various signaling kinases were

screened; the results indicate that 2,6-DMBQ strongly inhibits the phosphorylation of AKT and p38

MAPK. Additionally, the growth kinetics of cells treated with an AKT or p38 MAPK inhibitor in combination with 2,6-DMBQ indicate that 2,6-DMBQ suppresses NSCLC cell growth and migration through

inhibition of AKT and p38 MAPK. Taken together, our results suggest that 2,6-DMBQ is a potential

anticancer reagent against NSCLC cells and could be useful for treating lung cancer patients.

ÖSSZEFOGLALÁS

Az AIDS kórfejlődésének vizsgálatára alkalmas modellállat a macska. Az ember

és a macska immundeficienciáját okozó vírusok (HIV és FIV) hasonlóak, egyéb

vírusaik, mint a macska-adenovírus, elősegítik a betegség progresszióját, együttes kezelésük nehéz. A szerzők vizsgálataiban a fermentált búzacsíra-alapú Avemar granulátum daganatellenes készítmény gátolta az akut és krónikus fertőzési modellekben a FIV szaporodását, apoptosis révén pusztította a FIV-termelő

sejteket. Az Avemar a macska-adenovírus replikációját normál sejtekben igen,

daganatos sejtekben minimálisan gátolta. A daganatos sejtekben és a vírusszaporodásban egyaránt szerepet játszó ribonukleotid reduktáz gátlása lehet a

közös pont a gátlási folyamatokban.

Abstract

Background:  Fermented wheat germ extract has been reported to exert various pharmacological activities,

including anti-oxidant, anti-cell growth and cell apoptosis in various cancer cells. Although 2,6-dimethoxy-1,4-

benzoquinone (2,6-DMBQ) is a benzoquinone compound and found in fermented wheat germ extract, its

anticancer effects and molecular mechanism(s) against gastric cancer have not been investigated.

Methods: Anticancer effects of 2,6-DMBQ were determined by MTT, soft agar, cell cycle and Annexin V analysis.

Potential candidate proteins were screened via in vitro kinase assay and Western blotting. mTOR knockdown cell

lines were established by lentiviral infection with shmTOR. The effect of 2,6-DMBQ on tumor growth was assessed

using gastric cancer patient-derived xenograft models.

Results: 2,6-DMBQ significantly reduced cell growth and induced G1 phase cell cycle arrest and apoptosis in gastric

cancer cells. 2,6-DMBQ reduced the activity of mTOR in vitro. The inhibition of cell growth by 2,6-DMBQ is

dependent upon the expression of the mTOR protein. Remarkably, 2,6-DMBQ strongly reduced patient-derived

xenograft gastric tumor growth in an in vivo mouse model.

Conclusions: 2,6-DMBQ is an mTOR inhibitor that can be useful for treating gastric cancer. It has therapeutic

implications for gastric cancer patients.

Keywords:  2,6-DMBQ, mTOR, p70S6K, Gastric cancer, Patient-derived xenograft

Bioactive compounds such as benzoquinone derivates presented in fermented wheat germ extract (FWGE) have several positive

effects on overall health status of humans and animals alike. Since available data regarding the antioxidant activity of FWGE are

limited, the aim of our study was to investigate its effects on the cellular redox homeostasis applying primary hepatocyte cell

cultures of rat origin. Cultures were challenged to lipopolysaccharide (LPS) treatment for 2 or 8 hours to trigger inflammatory

response. Further, culture media were concomitantly supplemented with or without FWGE (Immunovet®, 0.1% and 1%). In

order to monitor the metabolic activity of the cell cultures, CCK-8 test was applied, while reactive oxygen species (ROS)

production was measured using Amplex Red method. Malondialdehyde concentration of culture media as a specific marker of

lipid peroxidation and the activity of glutathione peroxidase in cell lysates were also determined to monitor the redox status of

the cultures. Based on our findings, it can be concluded that FWGE did not show cytotoxic effects in any applied concentration

in cell cultures. Furthermore, FWGE efficiently decreased cellular ROS production and lipid peroxidation rate in case of LPSinduced inflammatory response. However, without LPS treatment, higher concentration of FWGE increased the rate of both

ROS and malondialdehyde synthesis. This observation may refer to the prooxidant activity of high dose FWGE, which is an

important beneficial effect regarding tumor cells. 

Summary

Preliminary studies which may be of signicance for research against

coronaviruses, including SARS-CoV-2, which has caused an epidemic

in China, are presented. An analysis was made of publicly available

data that contain information about important metabolites neutralizing

coronaviruses. Preliminary studies show that especially Ficus, barley,

thistle and sundew should be additionally tested with the aim of producing

medicines for coronavirus.

Key words: coronavirus, meta-analysis, avonoids, rhoifolin, pectolinarin,

herbacetin, ANOVA, Tukey's HSD test, barley, Ficus, thistle, sundew,

wheat, soybean, Brachypodium distachyon

The effect of fermented wheat germ extract (FWGE) (Immunovet®) was evaluated with cotreatments with deoxynivalenol (DON)

and T-2 toxin (T-2). These mycotoxins are produced by Fusarium mold species. The effects of FWGE on IPEC-J2 with DON and T2 have not been studied until now. The IPEC-J2 porcine, nontumorigenic cell line was selected to investigate the outcome of the

individually and simultaneously added compounds, as it has in vivo-like properties. The cells were treated for 24 h with the

selected solutions; then, the IPEC-J2 cells were allowed to regenerate in a culture medium for an additional 24 h. In our results,

DON and T-2 significantly increased the adverse impacts on cell viability and integrity of the cell monolayer. To elucidate the

extent of oxidative stress, extracellular H2O2 concentrations and intracellular reactive oxygen species (ROS) were measured.

FWGE appeared to be beneficial to IPEC-J2 cells given the separately and significantly decreased ROS levels. 1% and 2% FWGE

could significantly reduce mycotoxin-induced oxidative stress. In conclusion, the results demonstrate that FWGE exerted

protective effects to counteract the oxidative stress-provoking properties of applied fusariotoxins in the nontumorigenic IPEC-J2

cell line.

Abstract

Introduction:  Glioblastoma (GBM) has poor survival with standard treatment. Experimental data suggest potential

for metabolic treatment with low carbohydrate ketogenic diet (KD). Few human studies of KD in GBM have been

done, limited by difficulty and variability of the diet, compliance, and feasibility issues. We have developed a novel

KD approach of total meal replacement (TMR) program using standardized recipes with ready-made meals. This

pilot study evaluated feasibility, safety, tolerability, and efficacy of GBM treatment using TMR program with “classic”

4:1 KD.

Method:  GBM patients were treated in an open-label study for 6 months with 4:1 [fat]:[protein + carbohydrate]

ratio by weight, 10 g CH/day, 1600 kcal/day TMR. Patients were either newly diagnosed (group 1) and treated

adjunctively to radiation and temozolomide or had recurrent GBM (group 2). Patients checked blood glucose and

blood and urine ketone levels twice daily and had regular MRIs. Primary outcome measures included retention,

treatment-emergent adverse events (TEAEs), and TEAE-related discontinuation. Secondary outcome measures were

survival time from treatment initiation and time to MRI progression

Abstract

The global cancer burden has increased, and about 9.6 million cancer-related deaths were recorded in 2018. Genetic makeup,

unhealthy lifestyle, urbanization, obesity, and dietary preferences are key risk factors associated with cancer incidence and

development. Next to lung cancer, colorectal cancer is the most perilous cancer type in terms of mortality rate. Diet plays a

major role in colorectal cancer risk. The consumption of vegetables, unprocessed cereals, fish product, and fermented foods are

associated with lower cancer risk, while raw and processed red meats and refined foods are associated with increased cancer

risk. The anti-cancer properties of fermented foods and their possible mechanisms are summarized in this review. Some studies

indicated that the consumption of fermented foods reduced the risk of cancer and improved the health status of cancer patients.

However, some other research findings suggested that the intake of fermented foods was not associated with reduced cancer

risk. Several signaling pathways (p38 MAPK, ERK1/2, energy deprivation, and death-receptor mediated pathways) are involved

in the anti-proliferative and growth suppressive properties of fermented foods. Overall, the literature survey suggested that the

consumption of fermented foods might reduce cancer risk and improve health status in association with other factors, such as

genetics and healthy lifestyle.

Keywords:  fermented foods; anticancer; apoptosis; inflammation; diet.

Practical Application: The manuscript summarizes the anti-cancer properties and possible mechanism of fermented foods,

which highlights the benefits of fermented foods.

Abstract  

This systematic review and meta-analysis aim to

evaluate the association of wheat germ interventions and

metabolic markers. An electronic search was performed by

mid-May 2019 in the PubMed, Google Scholar, and Web

of Science databases. Quality was evaluated using the risk

of bias assessment tools. Thirty-three randomized controlled trials (RCTs) were identified, among which ten were

suitable and systematically reviewed based on biomarkers

(cholesterol, triglycerides, glucose, and oxidative stress).

Three biomarkers in five eligible studies were investigated

by meta-analysis. Total cholesterol showed non-significant

results (p = 0.98), with standard mean difference (SMD) of

- 0.01 (95% confidence interval; - 0.17, 0.16). The SMD

was - 0.06 (95% CI - 0.41, 0.29, n = 4) for triglycerides

and - 0.09 (95% CI - 0.62, 0.45, n = 2) for glucose. No

biomarkers showed heterogeneity (0%). This review

revealed non-significant association between wheat germ

interventions and metabolic markers. Sensitive analysis

with high-quality RCTs may be worth trying.

Keywords 

Wheat germ  Metabolic markers

Cholesterol  Triglycerides  Glucose

ABSTRACT

2,6-Dimethoxy-1,4-benzoquinone is a natural phytochemical

present in fermented wheat germ. It has been reported to exhibit anti-inflammatory, antitumor, and antibacterial activities. However, the anti-adipogenic effects of 2,6-dimethoxy1,4-benzoquinone and the mechanisms responsible have not

previously been elucidated. Such findings may have ramifications for the treatment of obesity. 2,6-Dimethoxy-1,4-benzoquinone (5 and 7.5 µM) significantly reduced the expression of

various adipogenic transcription factors, including peroxisome

proliferator-activated receptor-γ and CCAAT/enhancer binding protein α as well as adipocyte protein 2 and fatty acid synthase. 2,6-Dimethoxy-1,4-benzoquinone upregulated AMPdependent protein kinase phosphorylation and inhibited the

mature form of sterol regulatory element-binding protein 1c.

Notably, 2,6-dimethoxy-1,4-benzoquinone attenuated mammalian target of rapamycin complex 1 activity in 3T3-L1 and

mouse embryonic fibroblast cells. These findings highlight a

potential role for 2,6-dimethoxy-1,4-benzoquinone in the

suppression of adipogenesis. Further studies to determine the

anti-obesity effects of 2,6-dimethoxy-1,4-benzoquinone in

animal models appear warranted.

ABSTRACT

Goldnanoparticles (AuNPs) have well applied in imaging and carriers of drugs and/or biomolecules for diseases

and cancers therapeutics, due to their tunable physicochemical properties, easy functionalized with biomolecules and biocompatibility. AuNPs conjugated with biopolymer such as collagen has been demonstrated that

increased the cell proliferation, migration and cell differentiation. Avemar (Ave) is a nutraceutical from natural

components and dietary supplement for healthcare of tumor related anorexia/cachexia. Moreover, Ave has revealed the excellent bio-efficacy of anti-proliferation, cell cycle disturbing and apoptosis induction in numerous

types of tumor cells in in vivo and in vitro. However, the effects of Ave on cellular uptake mechanisms still

unclear. In this study, we fabricate the Ave-deposited AuNP-collagen nanocarrier (AuNP-Col-Ave) and investigate their endocytic mechanisms in transformed SCC oral cancer cells and non-transformed BAEC and HSF

cell lines. By using DLS assay, Ave-deposited AuNP-Col have shown a particle size of 303 ± 35.2 nm. Both

UV–vis absorption assay and FTIR spectrum analysis were also demonstrated that the Ave conjugated onto

AuNP-Col. Further, both MTT assay and Calcein AM assay were revealed that AuNP-Col-Ave induced a significant cytotoxicity in cancerous SCC cells and showed nontoxicity and biocompatibility for non-transformed

BAEC and HFS cells. In addition, AuNP-Col-Ave has showed an excellent uptake capacity in all these cell lines as

compared to AuNP-Col group. 

Cereals are one of the major food sources in human diet and a large quantity of by-products is generated throughout their processing chain. These by-products mostly consist of the germ and outer layers (bran), deriving from dry and wet milling of grains, brewers' spent grain originating from brewing industry, or others originating during bread-making and starch production. Cereal industry by-products are rich in nutrients, but still they end up as feed, fuel, substrates for biorefinery, or waste. The above uses, however, only provide a partial recycle. Although cereal processing industry side streams can potentially provide essential compounds for the diet, their use in food production is limited by their challenging technological properties. For this reason, the development of innovative biotechnologies is essential to upgrade these by-products, potentially leading to the design of novel and commercially competitive functional foods. Fermentation has been proven as a very feasible option to enhance the technological, sensory, and especially nutritional and functional features of the cereal industry by-products. Through the increase of minerals, phenolics and vitamins bioavailability, proteins digestibility, and the degradation of antinutritional compounds as phytic acid, fermentation can lead to improved nutritional quality of the matrix. In some cases, more compelling benefits have been discovered, such as the synthesis of bioactive compounds acting as antimicrobial, antitumoral, antioxidant agents. When used for baked-goods manufacturing, fermented cereal by-products have enhanced their nutritional profile.

Abstract:  Wheat germ is rich in quinones that exist as glycosides. In this study, we used Celluclast

1.5L to release the hydroxyquinones, which turn into benzoquinone, and prepared the water extract

from enzyme-treated wheat germ (EWG). We investigated whether enzyme treatment altered

the anti-inflammatory activity compared to the water extract of untreated wheat germ (UWG).

UWG inhibited the production of inducible nitric oxide synthase (iNOS) and interleukin (IL)-12 and

induced the production of IL-10 and heme oxygenase (HO)-1 in lipopolysaccharide (LPS)-stimulated

macrophages. Enzyme treatment resulted in greater inhibition of iNOS and IL-10 and induction of

HO-1 compared to UWG, possibly involving the modulation of nuclear factor (NF)-κB, activator protein

1 (AP-1) and nuclear factor erythroid 2-related factor (Nrf2). Mice fed UWG or EWG had decreased

serum tumor necrosis factor (TNF)-α and increased serum IL-10 levels after intraperitoneal injection

of LPS, with UWG being more effective for IL-10 and EWG more effective for TNF-α. Hepatic HO-1

gene was only expressed in mice fed EWG. We provide evidence that enzyme treatment is a useful

biotechnology tool for extracting active compounds from wheat germ.

Keywords: wheat germ; enzyme; benzoquinone; inflammation; macrophages

Abstract

The diagnosis of cancer in a child leaves parents and families devastated and vulnerable. In an effort to do

everything possible, families often choose an integrative medicine approach to their child’s care. Surveys have

found that 31%–84% of children with cancer use complementary and alternative medicine and most often as

supportive care agents. Several systematic reviews have demonstrated a clinical benefit for some select therapies;

however, the safety and efficacy of the combination of biological therapies with conventional treatment remain

largely unknown and garner concern due to the potential for interactions with conventional therapy. Given the

sustained use and potential benefit of integrative medicine, additional research is warranted in pediatric oncology.

Utilizing the available literature, clinical providers should aim to conduct open and nonjudgmental discussions

with families about the use of integrative medicine so as to guide the safe integration of the two modalities.

Keywords:  integrative medicine, nutrition, complementary/alternative medicine, pediatrics, cancer

Abstract.  Avemar, a derivative of fermented wheat germ

extract, is a non-toxic and natural compound that is used as

a dietary supplement by cancer patients undergoing chemotherapy and radiotherapy. Avemar has numerous biological

activities, and several recent studies have reported that it

may also have metastatic and anti-angiogenic effects. In the

present study, the mechanism of the anti-angiogenic effect of

Avemar on human cancer cells was investigated. The human

cell lines NCI-N87 (gastric tubular adenocarcinoma), PC3

(prostate carcinoma), HeLa (endocervical adenocarcinoma)

and A549 (lung adenocarcinoma) were treated with various

doses (400, 800, 1,600 and 3,200 µg/ml) of Avemar, and the

changes in mRNA and protein levels of two important markers

of angiogenesis, vascular endothelial growth factor (VEGF)

and cyclooxygenase-2 (Cox-2), were assessed by reverse transcription-quantitative polymerase chain reaction and ELISA.

VEGF and Cox‑2 protein and mRNA levels were significantly

lower in Avemar-treated cells than in untreated cells. The

data suggest that Avemar may exert an anti-angiogenic effect

on cancer cells. Thus, it is suggested to medical doctors as a

potential agent for the anti-angiogenic treatment of cancer.

Abstract  – Recent scientific researches proved a strong link between the diet adapted and the prevalence

of some diseases (cardiovascular diseases, diabetes, obesity…). The use of functional products may

contribute in solving this problem. Wheat is a cereal quite present in Mediterranean diet as it has an

energetic and nutritional interest (proteins, carbohydrate, fibers, vitamins…). Consumers in occidental

countries become more and more interested by mini-processed, without chemicals, natural, safe food

products. Sprouts are in agreement with this trend. Sprouting is a physiological event where a complex

nutrients transfer occurs. The aim of this review was to describe sprouting process and its impact on

nutritional properties of wheat seeds. During germination, storage molecules (proteins, starch) are

degraded under enzymatic action. Added to, some bioactive compounds such as polyphenols,

vitamins… are newly synthesized. Altogether, contribute in improving wheat nutritional quality.

Sprouting affects also functional and sensory properties of wheat. All modifications occurring during

sprouting make sprouted wheat seeds a functional ingredient, naturally enhanced by bioactive

molecules. Its use in food industry would provide an added value. 

Keywords: Wheat, Sprouting, Functional ingredient, Bioactive compounds, Wheat Technology

Abstract

Non-Hodgkin lymphoma (NHL) affects over 400,000 people in the United States; its incidence increases with age. Treatment options are numerous and expanding, yet efficacy is

often limited by toxicity, particularly in the elderly. Nearly 70% patients eventually die of the

disease. Many patients explore less toxic alternative therapeutics proposed to boost antitumor immunity, despite a paucity of rigorous scientific data. Here we evaluate the lymphomacidal and immunomodulatory activities of a protein fraction isolated from fermented

wheat germ. Fermented wheat germ extract was produced by fermenting wheat germ with

Saccharomyces cerevisiae. A protein fraction was tested for lymphomacidal activity in vitro

using NHL cell lines and in vivo using mouse xenografts. Mechanisms of action were

explored in vitro by evaluating apoptosis and cell cycle and in vivo by immunophenotyping

and measurement of NK cell activity. Potent lymphomacidal activity was observed in a panel

of NHL cell lines and mice bearing NHL xenografts. This activity was not dependent on

wheat germ agglutinin or benzoquinones. Fermented wheat germ proteins induced apoptosis in NHL cells, and augmented immune effector mechanisms, as measured by NK cell killing activity, degranulation and production of IFNγ. Fermented wheat germ extract can be

easily produced and is efficacious in a human lymphoma xenograft model. The protein fraction is quantifiable and more potent, shows direct pro-apoptotic properties, and enhances

immune-mediated tumor eradication. The results presented herein support the novel concept that proteins in fermented wheat germ have direct pro-apoptotic activity on lymphoma

cells and augment host immune effector mechanisms.

Abstract:  Fermented wheat germ extract (FWGE; trade name AVEMAR) is a natural compound

derived from industrial fermentation of wheat germ. Its potential anticancer properties has emerged

from recent studies. The aim of this systematic review is to summarize the data available in the

scientific literature concerning the in vitro activity of FWGE on malignant cells. A systematic review

of English articles in electronic databases has been performed. The primary outcomes of the review

regarded types of cancer cell lines subjected to the investigation and the main results concerning cell

viability, proliferation, and apoptosis observed within the studies. Sixteen articles were included in

the final qualitative analysis. Various types of cancer cells treated with FWGE have been analyzed,

showing mainly cytotoxic effects, alteration of the cell cycle, antiproliferative effects, and induction of

apoptosis. FWGE can be a promising drug component in cancer treatment; however, further in vitro

and in vivo studies are necessary to prove its effectiveness and safety in humans.

Keywords: FWGE; AVEMAR; fermented wheat germ extract; nutraceuticals; cancer treatment

Abstract

Wheat grains and its fractions contain significant level of antioxidant activity and many

phytochemicals, such as phenolic acids (ferulic and vanillic acids), carotenoids, and

tocopherol are beneficial in curing many disorders. The beneficial phytochemicals

are mostly present in aleurone fraction of wheat bran. The phytochemicals and antioxidants present in wheat have several health benefits, such as their ability to act as

antioxidants, immunoenhancers, and inhibitors of certain lesions, which have been

demonstrated for phenolic. Many wheat antioxidants are similar to the antioxidants

present in wheat, but their characteristics are also unique in nature. The regular consumption of these antioxidant compounds in whole grains is associated with a reduced

risk of many heart diseases and several forms of cancers and improves the regulation of

blood glucose. Wheat antioxidants play a vital role in bakery industry mostly in bread

industry. People are getting aware to use the bakery products that are prepared from

the white flour due to proper nutrition, healthy lifestyle, improved nutritional composition, and functional properties. In nutshell, wheat antioxidants including phytochemicals synergistically improve the health status of consumers by consuming the products

having complete nutrition.

Keywords:  wheat antioxidants, phytochemicals, bakery products, health perspectives