PMID: 

Pol Merkur Lekarski. 2020 Apr 22 ;48(284):120-123. PMID: 32352945

Abstract Title: 

[An association of selected polymorphisms of the lactoferrin gene and genes for lactoferrin receptors in the prevalence of metabolic disorders in obese subjects].

Abstract: 

Lactoferrin is a multipotent protein that belongs to the transferrin family. It was first isolated from cow's milk in 1939. In the 1960s, it was also found in breast milk. In the human body, lactoferrin can also be found in other body fluids, e.g., saliva, tears, and vaginal discharge. Its biological activity depends on receptors present on the membrane surface of many cells, such as neutrophils, hepatocytes, and intestinal epithelial cells. Lactoferrin can bind iron. Because of this property, it also has antibacterial, antiviral, and antifungal activity. Its antiinflammatory and anticancer activity has also been confirmed. Recent studies have demonstrated that lactoferrin might have a beneficial effect in the prevention and treatment of obesity-related metabolic abnormalities, such as type 2 diabetes, hypertension, and dyslipidaemia. It is also worth to notice the potential relationship between polymorphisms in lactoferrin gene, genes for lactoferrin receptors and metabolic abnormalities in obese subjects.

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PMID: 

Pharmaceutics. 2020 May 8 ;12(5). Epub 2020 May 8. PMID: 32397266

Abstract Title: 

Lactoferrin Contributes a Renoprotective Effect in Acute Kidney Injury and Early Renal Fibrosis.

Abstract: 

Patients with acute kidney injury (AKI) who survive the acute stage are at notable risk for chronic kidney disease (CKD) progression. There is no single therapy that can effectively prevent the AKI to CKD transition. Autophagy is a cytoplasmic component degradation pathway and has complex functions in several diseases, such as renal fibrosis. Previous research has shown that lactoferrin has important functions in antioxidant defense and other defense systems, protecting kidneys against various injuries. The present study investigated the effect of lactoferrin in protecting against the AKI to CKD transition. We identified 62 consensus genes with two-fold changes in clinical kidney tissues from AKI and CKD patients. Among the 62 overlay genes, the mRNA levels of LTF were significantly upregulated in the kidney tissues of AKI and CKD patients. Lactoferrin induced autophagy via the activation of the AMPK and inhibition of Akt/mTOR pathway in human kidney proximal tubular cells. Lactoferrin suppressed oxidative stress-induced cell death and apoptosis by augmenting autophagy. Lactoferrin has an antifibrotic role in human kidney tubular cells. In a mouse model of folic acid-induced AKI to CKD transition, treatment with lactoferrin recovered renal function and further suppressed renal fibrosis through the inhibition of apoptosis and the induction of autophagy. These findings identify lactoferrin as a potential therapeutic target for the prevention of the AKI to CKD transition.

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PMID: 

Biochem Cell Biol. 2020 May 13. Epub 2020 May 13. PMID: 32402212

Abstract Title: 

Lactoferrin Reduces Mycobacterial Trehalose 6,6'-dimycolate Induced M1-type Inflammation and Permits Fluoroquinolone Entry to Granulomas.

Abstract: 

Primary Mycobacterium tuberculosis (Mtb) infection results in the formation of a densely packed granulomatous response that essentially limits entry and efficacy of immune effector cells. Furthermore, the physical nature of the granuloma does not readily permit entry of therapeutic agents to sites where organisms reside. The Mtb cell wall mycolic acid, trehalose 6,6'-dimycolate (TDM), is a physiologically-relevant molecule to model macrophage mediated events during establishment of the tuberculosis-induced granuloma pathogenesis. No current therapeutic modalities focus to modulate host immune responses to ameliorate tuberculosis disease. Previous studies identified lactoferrin (LF), a natural iron-binding protein proven to modulate inflammation, as able to ameliorate granuloma cohesiveness. Therefore, a series of studies were enabled to further examine the effect of recombinant human LF (rHLF) on histological progression of the TDM-induced pathology. Treatment with rHLF demonstrated significant reduction in size and number of inflammatory foci following TDM injection, with reduced pulmonary pro-inflammatory cytokines TNF-α and IL-1β. LF allowed greater penetration of fluoroquinolone therapeutic to sites of pathology; TDM alone treated mice demonstrated exclusion of ofloxacin to regions of inflammatory response, whereas rHLF treated animals demonstrated increased penetration to responding foci. Finally, recent findings support the hypothesis that this mycobacterial mycolic acid can specifically recruit M1-like polarized macrophages; rHLF treatment was shown to limit the level of this M1-like phenotypic recruitment, corresponding highly with the occurrence of the decreased inflammatory response.

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PMID: 

Lancet Child Adolesc Health. 2020 May 11. Epub 2020 May 11. PMID: 32407710

Abstract Title: 

The effect of lactoferrin supplementation on death or major morbidity in very low birthweight infants (LIFT): a multicentre, double-blind, randomised controlled trial.

Abstract: 

BACKGROUND: Very low birthweight or preterm infants are at increased risk of adverse outcomes including sepsis, necrotising enterocolitis, and death. We assessed whether supplementing the enteral diet of very low-birthweight infants with lactoferrin, an antimicrobial protein, reduces all-cause mortality or major morbidity.METHODS: We did a multicentre, double-blind, pragmatic, randomised superiority trial in 14 Australian and two New Zealand neonatal intensive care units. Infants born weighing less than 1500 g and aged less than 8 days, were eligible and randomly assigned (1:1) using minimising web-based randomisation to receive once daily 200 mg/kg pasteurised bovine lactoferrin supplements or no lactoferrin supplement added to breast or formula milk until 34 weeks' post-menstrual age (or for 2 weeks, if longer), or until discharge from the study hospital if that occurred first. Designated nurses preparing the daily feeds were not masked to group assignment, but other nurses, doctors, parents, caregivers, and investigators were unaware. The primary outcome was survival to hospital discharge or major morbidity (defined as brain injury, necrotising enterocolitis, late-onset sepsis at 36 weeks' post-menstrual age, or retinopathy treated before discharge) assessed in the intention-to-treat population. Safety analyses were by treatment received. We also did a prespecified, PRISMA-compliant meta-analysis, which included this study and other relevant randomised controlled trials, to estimate more precisely the effects of lactoferrin supplementation on late-onset sepsis, necrotising enterocolitis, and survival. This trial is registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12611000247976.FINDINGS: Between June 27, 2014, and Sept 1, 2017, we recruited 1542 infants; 771 were assigned to the intervention group and 771 to the control group. One infant who had consent withdrawn before beginning lactoferrin treatment was excluded from analysis. In-hospital death or major morbidity occurred in 162 (21%) of 770 infants in the intervention group and in 170 (22%) of 771 infants in the control group (relative risk [RR] 0·95, 95% CI 0·79-1·14; p=0·60). Three suspected unexpected serious adverse reactions occurred; two in the lactoferrin group, namely unexplained late jaundice and inspissated milk syndrome, but were not attributed to the intervention and one in the control group had fatal inspissated milk syndrome. Our meta-analysis identified 13 trials completed before Feb 18, 2020, including this Article, in 5609 preterm infants. Lactoferrin supplements significantly reduced late-onset sepsis (RR 0·79, 95% CI 0·71-0·88; p

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n/a

PMID: 

. PMID: 32440345

Abstract Title: 

Anti-neoplastic and Immunomodulatory Potency of Co-Treatment Based on Bovine Lactoferrin and/or Muramyl Dipeptide in Tumor-Bearing Mice

Abstract: 

The current study investigates anti-neoplastic and immunomodulatory activities of co-treatment based on bovine lactoferrin (bLF) and/or muramyl dipeptide (MDP) with or without cisplatin (Cis) in tumor-bearing mice. In the present study, bLF (100 mg/kg; orally) and MDP (0.5 mg/kg; subcutaneously) was administered alone or together. MDP or bLF was co-treated with Cis (1 mg/kg; intraperitoneally) in mice-bearing Ehrlich solid carcinoma. Tumor size, tumor mass proliferation, apoptosis using immunohistochemistry, the alteration in spleen cell proliferation, phenotype using flow cytometry and white blood cells total and differential counts were detected. Treatment with Cis or (bLF and MDP) significantly reduced tumor size, upregulated the pro-apoptotic p53 expression and downregulated the anti-apoptotic Bcl-2 and proliferative marker PCNA expression compared to non-treated tumor-bearing animals. Moreover, co-treatment of MDP and Cis significantly potentiated the reduction of the tumor size, downregulated the Bcl-2 and PCNA expression and upregulated the p53 expression compared to Cis-treated animals. While bLF and Cis co-treatment positively controlled PCNA and p53 expression compared to tumor-bearing animals, it significantly potentiated the reduction of the tumor size and downregulated the Bcl-2 expression compared to Cis-treated animals. Co-treatment of (bLF and MDP), (bLF and Cis) or (MDP and Cis) increased the spleen cell proliferation and altered the immunological profile of the CD3+CD4+, CD3+CD8+, CD3+CD4+CD69+, CD3+CD8+CD69+ and CD11b+Ly6G+ cells to achieve better immune response against tumor. In conclusion, co-treatments based on bLF and/or MDP are promising therapies against cancer, through their potency to control proliferation, enhance apoptosis and improve the immune status against tumor cells.

A growing chorus of ordinary citizens and world-renowned medical and scientific experts is raising questions about matters ranging from the coronavirus’s origins to the rationale for lockdowns

PMID: 

Can J Cardiol. 2020 Apr 28. Epub 2020 Apr 28. PMID: 32360196

Abstract Title: 

Reversal of cardiac hypertrophy with a ketogenic diet in a child with mitochondrial disease and hypertrophic cardiomyopathy.

Abstract: 

Mitochondrial diseases are rare metabolic disorders which can cause hypertrophic cardiomyopathy. We describe a 3-year-old girl who was diagnosed for mitochondrial disease (mutation m.5559A>G in the mitochondrial-tRNAgene (MT-TW)). Echocardiography showed left ventricular hypertrophy with an enlarged septum (9 mm, Z-score 3.26). Antioxidant supplementation associated with a high-fat ketogenic diet were introduced and improved, as expected, neurological status. In addition, heart parameters improved with a normalization of interventricular septum thickness at the age of six (6 mm, Z-score 1.05). This case report suggests that a ketogenic diet may improve hypertrophic cardiomyopathy in the context of mitochondrial disease.

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PMID: 

Nutrients. 2020 Apr 30 ;12(5). Epub 2020 Apr 30. PMID: 32365746

Abstract Title: 

Effects of a Ketogenic Diet Containing Medium-Chain Triglycerides and Endurance Training on Metabolic Enzyme Adaptations in Rat Skeletal Muscle.

Abstract: 

Long-term intake of a ketogenic diet enhances utilization of ketone bodies, a particularly energy-efficient substrate, during exercise. However, physiological adaptation to an extremely low-carbohydrate diet has been shown to upregulate pyruvate dehydrogenase kinase 4 (PDK4, a negative regulator of glycolytic flux) content in skeletal muscle, resulting in impaired high-intensity exercise capacity. This study aimed to examine the effects of a long-term ketogenic diet containing medium-chain triglycerides (MCTs) on endurance training-induced adaptations in ketolytic and glycolytic enzymes of rat skeletal muscle. Male Sprague-Dawley rats were placed on either a standard diet (CON), a long-chain triglyceride-containing ketogenic diet (LKD), or an MCT-containing ketogenic diet (MKD). Half the rats in each group performed a 2-h swimming exercise, 5 days a week, for 8 weeks. Endurance training significantly increased 3-oxoacid CoA transferase (OXCT, a ketolytic enzyme) protein content in epitrochlearis muscle tissue, and MKD intake additively enhanced endurance training-induced increases in OXCT protein content. LKD consumption substantially increased muscle PDK4 protein level. However, such PDK4 increases were not observed in the MKD-fed rats. In conclusion, long-term intake of ketogenic diets containing MCTs may additively enhance endurance training-induced increases in ketolytic capacity in skeletal muscle without exerting inhibitory effects on carbohydrate metabolism.

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PMID: 

Int J Mol Sci. 2020 May 2 ;21(9). Epub 2020 May 2. PMID: 32370212

Abstract Title: 

Short-Term Physiological Effects of a Very Low-Calorie Ketogenic Diet: Effects on Adiponectin Levels and Inflammatory States.

Abstract: 

Adipose tissue is a multifunctional organ involved in many physiological and metabolic processes through the production of adipokines and, in particular, adiponectin. Caloric restriction is one of the most important strategies against obesity today. The very low-calorie ketogenic diet (VLCKD) represents a type of caloric restriction with very or extremely low daily food energy consumption. This study aimed to investigate the physiological effects of a VLCKD on anthropometric and biochemical parameters such as adiponectin levels, as well as analyzing oligomeric profiles and cytokine serum levels in obese subjects before and after a VLCKD. Twenty obese subjects were enrolled. At baseline and after eight weeks of intervention, anthropometric and biochemical parameters, such as adiponectin levels, were recorded. Our findings showed a significant change in the anthropometric and biochemical parameters of these obese subjects before and after a VLCKD. We found a negative correlation between adiponectin and lipid profile, visceral adipose tissue (VAT), C-reactive protein (CRP), and pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), which confirmed the important involvement of adiponectin in metabolic and inflammatory diseases. We demonstrated the beneficial short-term effects of a VLCKD not only in the treatment of obesity but also in the establishment of obesity-correlated diseases.

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PMID: 

Nutr Hosp. 2020 May 7. Epub 2020 May 7. PMID: 32379476

Abstract Title: 

[Multidisciplinary methodology and ketogenic diet in real clinical practice: efficacy and rapidity in weight loss. Survival Analysis PROMET Lipoinflammation study].

Abstract: 

OBJECTIVE: the aim of the current work was to evaluate the response time to a method of weight loss that includes dietary guidelines, physical exercise and emotional support. The response was defined as a loss of 10% of the baseline weight.METHODS: data was obtained from the patients' record recruited in Promet Lipoinflamación, an observational study of real world data in obese or overweight patients treated with a multidisciplinary method and based initially on a very-low-calorie ketogenic (VLCK) diet. Weight loss rate was evaluated through a survival analysis Kaplan-Meier and related factors through Cox regression).RESULTS: 6,369 subjects were included and 74.4% managed to reach a weight loss of 10% in a mean time of 57.64 days (IC 95%: 56.95-58.33). The factors associated with a greater probability of reaching a loss of 10% or more were male gender (RR: 1.37, p

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