Ketogenic, hypocaloric diet improves nonalcoholic steatohepatitis.

PMID: 

J Transl Int Med. 2020 Mar ;8(1):26-31. Epub 2020 May 9. PMID: 32435609

Abstract Title: 

Ketogenic, Hypocaloric Diet Improves Nonalcoholic Steatohepatitis.

Abstract: 

Background and objectives: Nonalcoholic steatohepatitis (NASH) is strongly associated with obesity. A weight loss of≥10% is necessary to improve NASH severity, but this goal has rarely been achieved in published studies using different diet protocols. The effect of a ketogenic, hypocaloric, commercial diet ("Ideal Protein,"IP) on body weight, metabolic markers, and liver tests in a group of NASH patients is evaluated in this study. Daily calorie intake was tailored to achieve a weight loss of≥10%.Methods: We analyzed 38 patients with NASH who were placed on the IP diet between 2014 and 2018 and compared their outcomes with 6 control patients who declined the diet. All patients were evaluated by a trained health coach in weekly intervals throughout the study period. Clinical and laboratory data obtained before and at 6.5 months after intervention were compared using paired t-testing.Results: The patients on the IP diet experienced a significant weight reduction (217± 8 lb. 194± 7 lb; mean ± S.E.M.), corresponding to an average weight loss of 9.7% ± 1.6%. Significant changes in systolic blood pressure (133 ± 3 mmHg. 123± 3 mmHg), triglycerides (200 ± 21 mmol/L. 132± 11 mmol/L), hemoglobin A1c (6.71% ± 0.29%. 5.74%± 0.19%), SGPT (97.3 ± 11.1 IU/L. 44.2± 5.9 IU/L), SGOT (82.4 ± 10.5 IU/L. 32.8± 5.2 IU/L), and Fib-4 scores (2.25 ± 0.23. 1.40± 0.13) were also observed (

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Ketogenic diets alter the gut microbiome resulting in decreased intestinal Th17 cells.

PMID: 

Cell. 2020 May 14. Epub 2020 May 14. PMID: 32437658

Abstract Title: 

Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells.

Abstract: 

Very low-carbohydrate, high-fat ketogenic diets (KDs) induce a pronounced shift in metabolic fuel utilization that elevates circulating ketone bodies; however, the consequences of these compounds for host-microbiome interactions remain unknown. Here, we show that KDs alter the human and mouse gut microbiota in a manner distinct from high-fat diets (HFDs). Metagenomic and metabolomic analyses of stool samples from an 8-week inpatient study revealed marked shifts in gut microbial community structure and function during the KD. Gradient diet experiments in mice confirmed the unique impact of KDs relative to HFDs with a reproducible depletion of bifidobacteria. In vitro and in vivo experiments showed that ketone bodies selectively inhibited bifidobacterial growth. Finally, mono-colonizations and human microbiome transplantations into germ-free mice revealed that the KD-associated gut microbiota reduces the levels of intestinal pro-inflammatory Th17 cells.Together, these results highlight the importance of trans-kingdom chemical dialogs for mediating the host response to dietary interventions.

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The ketogenic diet regimen is considered to be a promising support therapy for patients with different types of advanced cancer.

PMID: 

Nutrients. 2020 May 19 ;12(5). Epub 2020 May 19. PMID: 32438645

Abstract Title: 

Promising Effect of a New Ketogenic Diet Regimen in Patients with Advanced Cancer.

Abstract: 

A ketogenic diet is expected to be an effective support therapy for patients with cancer, but the degree and duration of carbohydrate restriction are unclear. We performed a case series study of a new ketogenic diet regimen in patients with different types of stage IV cancer. Carbohydrates were restricted to 10 g/day during week one, 20 g/day from week two for three months, and 30 g/day thereafter. A total of 55 patients participated in the study, and data from 37 patients administered the ketogenic diet for three months were analyzed. No severe adverse events associated with the diet were observed. Total ketone bodies increased significantly, and both fasting blood sugar and insulin levels were suppressed significantly for three months after completion of the study. Five patients showed a partial response on Positron emission tomography-computed tomography (PET-CT) at three months. Three and seven patients showed complete and partial responses, respectively at one year. Median survival was 32.2 (maximum: 80.1) months, and the three-year survival rate was 44.5%. After three months on the ketogenic diet, the serum Alb, BS, and CRP (ABC) score could be used to stratify the patients into groups with significantly different survival rates (

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Survival outcomes of metabolically supported chemotherapy combined with ketogenic diet, hyperthermia, and hyperbaric oxygen therapy in advanced gastric cancer.

PMID: 

Niger J Clin Pract. 2020 May ;23(5):734-740. PMID: 32367884

Abstract Title: 

Survival outcomes of metabolically supported chemotherapy combined with ketogenic diet, hyperthermia, and hyperbaric oxygen therapy in advanced gastric cancer.

Abstract: 

Background: Survival outcomes are still far from being satisfactory in patients with advanced gastric cancer, despite availability of novel chemotherapeutic regimens.Aim: This study evaluated the outcomes of patients with advanced gastric cancer who received chemotherapy along with additional treatment modalities targeting multiple tumor cell vulnerabilities.Materials and Methods: A total of 24 patients diagnosed with stage III-IV locally advanced or metastatic gastric adenocarcinoma that received metabolically supported chemotherapy (MSCT) combined with ketogenic diet, local hyperthermia, and hyperbaric oxygen therapy (HBOT) between April 2014 and October 2017 were included in this retrospective study. Survival outcomes were evaluated.Results: In 22 patients (88.0%), complete response was achieved. Mean duration of follow-up was 23.9± 12.7 months. Mean overall survival was 39.5 months (95% confidence interval [CI]: 28.1-51.0) and mean progression free survival was 36.5 months (95% CI: 25.7-47.2). No problems were encountered due to fasting, hypoglycemia, ketogenic diet, hyperthermia or HBOT.Conclusions: The combination treatment used in this study (MSCT together with a ketogenic diet, hyperthermia and HBOT) appears to be promising in the treatment of advanced gastric cancer. Further research and comparative clinical trials are warranted to support and standardize this novel treatment protocol.

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Hyperbaric oxygenation therapy minimizes deleterious effects of irradiation on flexural strength and the bone stiffness analysis.

PMID: 

Radiat Oncol. 2020 May 6 ;15(1):95. Epub 2020 May 6. PMID: 32375798

Abstract Title: 

The effect of hyperbaric oxygen therapy on bone macroscopy, composition and biomechanical properties after ionizing radiation injury.

Abstract: 

BACKGROUND: Radiotherapy used in tumor treatment compromises vascularization of bone tissue. Hyperbaric oxygenation (HBO) increases oxygen availability and improves vascularization, minimizing the deleterious effects of ionizing radiation (IR). Therefore, the aim of this study was to evaluate HBO therapy effect on bone macroscopy, composition and biomechanical properties after IR damage.METHODS: Twenty male Wistar rats weighing 300 ± 20 g (10 weeks of age) were submitted to IR (30 Gy) to the left leg, where the right leg was not irradiated. After 30 days, ten animals were submitted to HBO therapy, which was performed daily for 1 week at 250 kPa for 90-min sessions. All animals were euthanized 37 days afterirradiation and the tibia were separated into four groups (n = 10): from animals without HBO – right tibia Non-irradiated (noIRnoHBO) and left tibia Irradiated (IRnoHBO); and from animals with HBO – right tibiae Non-irradiated (noIRHBO) and left tibia Irradiated (IRHBO). The length (proximal-distal) and thickness (anteroposterior and mediolateral) of the tibiae were measured. Biomechanical analysis evaluated flexural strength and stiffness. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) was used to calculate the amide I ratio, crystallinity index, and matrix to mineral ratios.RESULTS: In the macroscopic and ATR-FTIR analysis, the IRnoHBO showed lower values of length, thickness and amide I ratio, crystallinity index and matrix to mineral ratios compared to noIRnoHBO (p  0.05). Biomechanics analysis showed that the IRnoHBO group had lower values of flexural strength and stiffness compared to noIRnoHBO and IRHBO groups (p 

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Hyperbaric oxygen therapy in preventing mechanical ventilation in COVID-19 patients.

PMID: 

J Wound Care. 2020 May 1 ;29(Sup5a):S4-S8. PMID: 32412891

Abstract Title: 

Hyperbaric oxygen therapy in preventing mechanical ventilation in COVID-19 patients: a retrospective case series.

Abstract: 

OBJECTIVE: A pandemic afflicts the entire world. The highly contagious SARS-CoV-2 virus originated in Wuhan, China in late 2019 and rapidly spread across the entire globe. According to the World Health Organization (WHO), the novel Coronavirus (COVID-19)has infected more than two million people worldwide, causing over 160,000 deaths. Patients with COVID-19 disease present with a wide array of symptoms, ranging from mild flu-like complaints to life threatening pulmonary and cardiac complications. Older people and patients with underlying disease have an increased risk of developing severe acute respiratory syndrome (SARS) requiring mechanical ventilation. Once intubated, mortality increases exponentially. A number of pharmacologic regimens, including hydroxychloroquine-azithromycin, antiviral therapy (eg, remdesevir), and anti-IL-6 agents (e.g., toclizumab), have been highlighted by investigators over the course of the pandemic, based on the therapy's potential to interrupt the viral life-cycle of SARS-CoV-2 or preventing cytokine storm. At present, there have been no conclusive series of reproducible randomised clinical trials demonstrating the efficacy of any one drug or therapy for COVID-19.CASES: COVID-19 positive patients (n=5) at a single institution received hyperbaric oxygen therapy (HBOT) between 13 and 20 April 2020. All the patients had tachypnoea and low oxygen saturation despite receiving high FiO. HBOT was added to prevent the need for mechanical ventilation. A standard dive profile of 2.0ATA for 90 minutes was employed. Patients received between one and six treatments in one of two dedicated monoplace hyperbaric chambers.RESULTS: All the patients recovered without the need for mechanical ventilation. Following HBOT, oxygen saturation increased, tachypnoea resolved and inflammatory markers fell. At the time of writing, three of the five patients have been discharged from the hospital and two remain in stable condition.CONCLUSION: This small sample of patients exhibited dramatic improvement with HBOT. Most importantly, HBOT potentially prevented the need for mechanical ventilation. Larger studies are likely to define the role of HBOT in the treatment of this novel disease.

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Puerarin alleviates lipopolysaccharide-induced myocardial fibrosis.

PMID: 

Cardiovasc Toxicol. 2020 Mar 31. Epub 2020 Mar 31. PMID: 32236896

Abstract Title: 

Puerarin Alleviates Lipopolysaccharide-Induced Myocardial Fibrosis by Inhibiting PARP-1 to Prevent HMGB1-Mediated TLR4-NF-κB Signaling Pathway.

Abstract: 

Myocardial fibrosis (MFs) is a crucial pathological process that results in cardiac failure in the development of multiple cardiovascular diseases. Puerarin could reportedly be used to treat a variety of cardiovascular diseases. However, the exact mechanism of puerarin on MFs was not clear enough. The separated primary cardiac fibroblasts (CFs) were induced by lipopolysaccharide (LPS) and treated with puerarin. The levels of TNF-α, IL-6, HMGB1, PARP-1, α-SMA, collagen-1, collagen-3, NF-κB pathways were examined by ELISA, immunofluorescence, RT-qPCR, western blot and immunohistochemistry assays. In addition, MFs rats' model was established using transverse aortic constriction (TAC), and the degree of fibrosis was certified by masson staining. We successfully separated primary CFs, and certified that LPS induction could upregulate the levels of PARP-1, HMGB1, inflammatory cytokines and fibrosis-related proteins (α-SMA, collagen-1 and collagen-3). In addition, we proved that puerarin could weaken MFs, and PARP-1 andHMGB1 expressions, which were induced by LPS in primary CFs. In terms of mechanism, HMGB1 expression could be promoted by PARP-1, and PARP-1 could attenuate the therapeutic effect of puerarin on LPS-induced MFs. Besides, PARP-1-HMGB1-NF-κB pathway was related to the protective effect of puerarin onMFs. In vivo, we also verified the protective efficacy of puerarin on MFs induced by TAC, and puerarin also regulated HMGB1-mediated TLR4-NF-κB signaling pathway. We demonstrated that puerarin could ameliorate MFs by downregulating PARP-1 to inhibit HMGB1-mediated TLR4-NF-κB signaling pathway inLPS-induced primary CFs and TAC-induced MFs rats' model.

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Puerarin may represent a chemopreventive and chemotherapeutic agent for liver cancer treatment.

PMID: 

Braz J Med Biol Res. 2020 ;53(4):e8882. Epub 2020 Mar 31. PMID: 32294699

Abstract Title: 

Puerarin inhibits hepatocellular carcinoma invasion and metastasis through miR-21-mediated PTEN/AKT signaling to suppress the epithelial-mesenchymal transition.

Abstract: 

Hepatocellular carcinoma (HCC) is one of the most common primary malignant tumors of the liver worldwide. Liver resection and transplantation are currently the only effective treatments; however, recurrence and metastasis rates are still high. Previous studies have shown that the epithelial-mesenchymal transition (EMT) is a key step in HCC invasion and metastasis. Inhibition of EMT has become a new therapeutic strategy for tumors. Recently, puerarin, a well-characterized component of traditional Chinese medicine, has been isolated from Pueraria radix and exerts positive effects on many diseases, particularly cancers. In this study, CCK-8, EdU immunofluorescence, colony formation, wound healing, and migration assays were used to detect the effects of puerarin on HCC cells. We further analyzed the relationship between puerarin and miR-21/PTEN/EMT markers in HCC cell lines. Our results showed that HCC cell proliferation, migration, invasion, tumor formation, and metastasis were reduced by puerarin in vitro and in vivo. Additionally, puerarin inhibited the EMT process of HCC by affecting the expression of Slug and Snail. Moreover, oncogenic miR-21 was inhibited by puerarin, coupled with an increase in the tumor suppressor gene PTEN. Increasing miR-21 expression or decreasing PTEN expression reversed the inhibition effects of puerarin in HCC. These data confirmed that puerarin affects HCC through the miR-21/PTEN/EMT regulatory axis. Overall, puerarin may represent a chemopreventive and/or chemotherapeutic agent for HCC treatment.

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